WO2020200831A1 - Automated voxel positioning for in vivo magnetic resonance spectroscopy - Google Patents

Automated voxel positioning for in vivo magnetic resonance spectroscopy Download PDF

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Publication number
WO2020200831A1
WO2020200831A1 PCT/EP2020/057712 EP2020057712W WO2020200831A1 WO 2020200831 A1 WO2020200831 A1 WO 2020200831A1 EP 2020057712 W EP2020057712 W EP 2020057712W WO 2020200831 A1 WO2020200831 A1 WO 2020200831A1
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magnetic resonance
voxel
resonance spectroscopy
processors
shim
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PCT/EP2020/057712
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French (fr)
Inventor
Lyubomir Georgiev ZAGORCHEV
Erin MACMILLAN
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Koninklijke Philips N.V.
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Publication of WO2020200831A1 publication Critical patent/WO2020200831A1/en

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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01RMEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
    • G01R33/00Arrangements or instruments for measuring magnetic variables
    • G01R33/20Arrangements or instruments for measuring magnetic variables involving magnetic resonance
    • G01R33/44Arrangements or instruments for measuring magnetic variables involving magnetic resonance using nuclear magnetic resonance [NMR]
    • G01R33/48NMR imaging systems
    • G01R33/54Signal processing systems, e.g. using pulse sequences ; Generation or control of pulse sequences; Operator console
    • G01R33/56Image enhancement or correction, e.g. subtraction or averaging techniques, e.g. improvement of signal-to-noise ratio and resolution
    • G01R33/565Correction of image distortions, e.g. due to magnetic field inhomogeneities
    • G01R33/56527Correction of image distortions, e.g. due to magnetic field inhomogeneities due to chemical shift effects
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/05Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves 
    • A61B5/055Detecting, 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
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01RMEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
    • G01R33/00Arrangements or instruments for measuring magnetic variables
    • G01R33/20Arrangements or instruments for measuring magnetic variables involving magnetic resonance
    • G01R33/28Details of apparatus provided for in groups G01R33/44 - G01R33/64
    • G01R33/38Systems for generation, homogenisation or stabilisation of the main or gradient magnetic field
    • G01R33/387Compensation of inhomogeneities
    • G01R33/3875Compensation of inhomogeneities using correction coil assemblies, e.g. active shimming
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01RMEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
    • G01R33/00Arrangements or instruments for measuring magnetic variables
    • G01R33/20Arrangements or instruments for measuring magnetic variables involving magnetic resonance
    • G01R33/44Arrangements or instruments for measuring magnetic variables involving magnetic resonance using nuclear magnetic resonance [NMR]
    • G01R33/48NMR imaging systems
    • G01R33/483NMR imaging systems with selection of signals or spectra from particular regions of the volume, e.g. in vivo spectroscopy
    • G01R33/485NMR 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

Definitions

  • the present invention is generally related to magnetic resonance spectroscopy.
  • Magnetic resonance imaging is a non-invasive imaging technology that produces detailed, three-dimensional anatomical images, such as brain anatomy images, using powerful magnets.
  • a patient is positioned within an MRI machine, and during the imaging process, the magnets are used to produce a strong magnetic field that forces protons in the body to align with the magnetic field.
  • protons within water nuclei of tissue are usually randomly oriented.
  • the applied magnetic field causes alignment (e.g., magnetization) of the protons, and radio frequency (RF) energy is used to disrupt the alignment.
  • RF energy is emitted and measured.
  • the time it takes for the protons to realign with the magnetic field and the amount of RF energy that is emitted is a function of the environment and chemical nature of molecules.
  • This energy exchange measured as an RF signal, is translated by a computing system into anatomical images by assigning different visual (e.g., gray-scale) levels according to the strength of the emitted signal.
  • the resulting MRI scans comprise thousands of volume/pixel elements (voxels), which reflect various magnetic properties of the tissues they contain, which a professional (e.g., doctor, including radiologist) interprets to make a diagnosis and prescribe the necessary treatment.
  • Magnetic resonance spectroscopy provides an additional layer of imaging technology to assist the doctor in enabling a suitable diagnosis/treatment.
  • An MRS system comprises a computing system that uses the MRI image data and various coils of the MRI machine to develop MRS spectra at a given site/volume of interest (e.g., at the voxel level).
  • MRS is the only imaging technique that can assess the levels of a wide range of biologically important chemicals in the human brain both non- invasively and without the use of ionizing radiation.
  • MRS enables detection of many biomarkers of neurological diseases and neurodegenerative disorders, including N- actetylaspartate (NAA), which is involved in myelin synthesis, creatine and phosphocreatine, which are involved in energy storage and mitochondrial function, myo-inositol, which is a marker of glial cell density and gliosis, and glutamate, which is the brain’s primary excitatory neurotransmitter.
  • NAA N- actetylaspartate
  • creatine and phosphocreatine which are involved in energy storage and mitochondrial function
  • myo-inositol which is a marker of glial cell density and gliosis
  • glutamate which is the brain’s primary excitatory neurotransmitter.
  • MRS is able to distinguish between these chemicals, and others, based on the resonant frequencies of their protons. Protons with different local magnetic fields, depending on their chemical neighbors, resonate at different frequencies, leading to a spectrum of proton frequencies detectable in
  • One object of the present invention is to provide a magnetic resonance spectroscopy system that mitigates signal artifacts arising from water and/or lipids.
  • a computing device determines whether magnetic resonance spectroscopy (MRS) voxel placement is proximal to a defined tissue boundary, and causes a change in a gradient direction, the change in gradient direction adjusting the placement of the MRS voxel away from the defined tissue boundary.
  • MRS magnetic resonance spectroscopy
  • the computing device receives an indication of a respective size for all dimensions of the at least one MRS voxel; determines a shim volume for the at least one MRS voxel, the shim volume increased in any dimension that is less than a threshold dimension; and responsive to at least a portion of the shim volume being proximal to the defined tissue boundary, causes a position of the shim volume to be adjusted relative to a default position, the adjustment causing the adjusted position of the shim volume to be further from the defined tissue boundary than the default position.
  • the vast majority of magnetic resonance spectroscopy scans neglect to control a location over which the magnetic field is homogenized, or namely, neglect to perform proper shimming.
  • FIG. 1 is a schematic diagram that illustrates an example environment in which an automated magnetic resonance spectroscopy (MRS) voxel planning system is used, in accordance with an embodiment of the invention.
  • MRS magnetic resonance spectroscopy
  • FIG. 2A is a block diagram that illustrates an example computing device implementing an automated MRS voxel planning system, in accordance with an embodiment of the invention.
  • FIG. 2B is a schematic diagram that illustrates an example brain model.
  • FIG. 3A is a block diagram that illustrates a mechanism to access MRS data from a magnetic resonance spectroscopy (MRS) voxel in an automated MRS voxel planning system of FIG. 2A, in accordance with an embodiment of the invention.
  • FIG. 3B is a schematic diagram that conceptually illustrates magnetic resonance spectroscopy localization, in accordance with an embodiment of the invention.
  • FIGS. 4A-4B are block diagrams that illustrate an example change in chemical shift displacement direction implemented by an automated MRS voxel planning system, in accordance with an embodiment of the invention.
  • FIGS. 5A-5B are block diagrams that illustrate an example change in shim volume positioning implemented by an automated MRS voxel planning system, in accordance with an embodiment of the invention.
  • FIG. 6 is a flow diagram that illustrates an example of an automated MRS voxel planning method, in accordance with an embodiment of the invention.
  • FIG. 7 is a flow diagram that illustrates an example of another automated MRS voxel planning method, in accordance with another embodiment of the invention.
  • MRS magnetic resonance spectroscopy
  • the MRS voxel planning system determines whether MRS voxel placement is proximal to a defined tissue boundary that comprises lipid and/or water that can reduce the reliability of the MRS data, and causes a change in a gradient direction. The change in gradient direction adjusts the placement of the MRS voxel away from the defined tissue boundary.
  • the MRS voxel planning system further automates shim volume placement in a manner that is offset from a default position, as set forth in the description below.
  • MRS voxel planning system of the present disclosure
  • N-actetylaspartate As a biomarker, which is popular for brain analysis, it should be appreciated by one having ordinary skill in the art, in the context of the present disclosure, that other biomarkers may be used for the brain or other biological structures.
  • MRS localization is described in the context of single MRS voxel techniques, multi-MRS voxel techniques may be used and hence are contemplated to be within the scope of the disclosure.
  • the description identifies or describes specifics of one or more embodiments, such specifics are not necessarily part of every embodiment, nor are all of any various stated advantages necessarily associated with a single embodiment.
  • An MRS voxel refers to a single, cuboidal region of interest for purposes of acquiring MRS data, and is either manually placed or automatically placed onto a segmented and categorized anatomical or biological image acquired by magnetic resonance imaging.
  • Chemical shift displacement refers to a difference in resonance frequencies of two otherwise identical nuclei present in different molecular environments that gives rise to a displacement in spatial locations for each chemical.
  • the molecular environment of 1 H protons of fat, nestled within long-chain triglycerides is different than the molecular environment of 1 H protons of water, which leads to a difference in spatial locations along, for instance, a magnetic resonance spectrum.
  • a localized MRS volume element e.g., an MRS voxel
  • RF radio frequency
  • a chemical shift displacement artifact comprises a condition where the chemical shift displacement for two or more substances that interface or are in close proximity to one another causes a mismapping or misregistration of a given chemical under investigation, since the chemical under investigation may be obscured by the signal contribution from content (e.g., water, lipids, etc.) from an unintended spatial location.
  • Shimming is also described herein, and in effect, comprises a volume (shim volume) over which the magnetic field is homogenized, where one of plural techniques may be used, including pencil beam shimming, among others.
  • FIG. 1 shown is an example environment in which an embodiment of an MRS voxel planning system is used, the environment comprising a magnetic resonance imaging (MRI) system 10.
  • MRI magnetic resonance imaging
  • FIG. 1 the MRI system 10 illustrated in FIG. 1 is merely illustrative of one example environment, and that in some
  • the MRI system 10 includes an MRI scanner 12, an MRS voxel planner 14, and an MRS analyzer 16, which is shown in communication with reference data memory 18 and one or more output devices (output device(s)) 20.
  • the MRI scanner 12 includes a main magnet 22, gradient (x, y and/or z) coils 24, shim coils 26, and an RF coil 28.
  • the gradient coils 24 may also be tasked as shim coils 26 (e.g., for first order or linear shimming).
  • the main magnet 22 (which can be a superconducting, resistive, permanent, or other type of magnet) produces a substantially homogeneous, temporally constant main magnetic field B 0 in an examination region 30.
  • the gradient coils 24 generate time varying gradient magnetic fields along the x, y and/or z-axes of the examination region 30.
  • the MRS voxel planning system changes the gradient direction to avoid undesired lipid and/or water at or near a tissue boundary.
  • the shim coils 26 are used to control magnetic field homogeneity over a given region of interest, including an MRS voxel, where a homogenous magnetic field is necessary to separate peaks in an MR spectrum.
  • the shim coils 26 are used in vivo to perform a process referred to as shimming to ensure that the B 0 magnetic field is homogenous, enabling narrower spectral lines (e.g., improved spectral resolution) from which reliable separation and quantification of chemicals can be achieved.
  • the shim coils 26 are generally comprised of multiple current loops connected in series and placed geometrically so that the magnetic field generated by them across a diameter spherical volume corresponds to a specific spherical harmonic.
  • the shim coil functionality corresponds to lower order spherical harmonics (e.g., X, Y, and Z shims) in cooperation with a standard gradient amplifier, applied as an offset to the gradient coils 24. All other higher order shim fields may be generated by the shim coils 26 using corresponding shim amplifiers.
  • Software in the MRS voxel planner 14 (or in the MRS analyzer 16 in some embodiments) control shimming based on received measures of magnetic field inhomogeneity to analytically determine the required shim currents.
  • shimming e.g., in vivo, active shimming
  • shimming comprises a minimization procedure in which there is an attempt to cancel the measured magnetic field (e.g., based on magnetic field maps) with the available spherical harmonic shims.
  • the RF coil 28 includes a transmission portion that transmits a radio frequency signal (e.g., at the Larmor frequency of nuclei of interest such as hydrogen, Helium, etc.) that excites the nuclei of interest in the examination region 30 and a receive portion that receives MR signals emitted by excited nuclei.
  • the transmission and receive portions can alternatively be located in separate coils.
  • An MR reconstructor 32 reconstructs the MR signals and generates MRI image data.
  • a subject support 34 supports a subject such as a human or animal patient in the examination region 30.
  • a general purpose computing system serves as an operator console 36 and includes an output device such as a display and an input device such as a keyboard, mouse, and/or the like. Software resident on the console 36 allows the operator to interact with the scanner 12, for example, to select an imaging protocol, to initiate scanning, etc.
  • a data repository 38 can be used to store the image data generated by the scanner 12 and/or other image data.
  • the illustrated data repository 38 may include one or more of a picture archiving and communication system (PACS), a radiology information system (RIS), a hospital information system (HIS), an electronic medical record (EMR) database, a server, a computer, and/or other data repository.
  • the data repository 38 can be local to the MRI system 10 or remote from the system 10.
  • the MRS voxel planner 14 is configured to automatically position a volume of interest, such as one or more MRS voxels, with respect to a (biological) structure segmented in MRI image data obtained from the scanner 12, the repository 38 and/or other source.
  • the automatic positioning includes adjustments in chemical shift direction and/or shim volume sizing and/or placement depending on the MRS voxel orientation and proximity to tissue boundaries possessing lipid and/or water.
  • the MRS voxel planner 14 is configured to operate in conjunction with manual positioning of MRS voxels, including automatic adjustments in the chemical shift direction and/or shim volume placement when the manual positioning is
  • the illustrated MRS voxel planner 14 receives an input signal, which can include indicia indicating an anatomical model of interest, particular segmented structure, a positioning rule of interest, and/or other information. As described further below, in one instance, the MRS voxel planner 14 utilizes this input to accurately and reproducibly position a volume of interest with respect to segmented structures in the MRI image data for subsequent (localized) MRS scanning and analysis and/or adjust a manual positioning of the volume of interest. The MRS voxel planner 14 also resizes and adjusts the positioning of a shim volume to avoid undesired tissue components (e.g., lipids or water).
  • tissue components e.g., lipids or water
  • the functions of the MRS voxel planner 14 can be implemented via a computing device having one or more processors executing one or more computer readable instructions encoded or embedded on a non-transitory, computer readable storage medium, including physical memory.
  • the MRS voxel planner 14 may reside in the console 36.
  • the MRS voxel planner 14 may reside external to the console 36 (e.g., at a remote computing device (e.g., a server) or at a local computing device (e.g., local server and/or workstation, laptop, etc.).
  • the MRS analyzer 16 analyzes the volume of interest based on the positioning of the MRS voxel planner 14. This includes performing magnetic resonance spectroscopy to quantify biochemical composition in the volume of interest with respect to the segmented structure and/or comparing the quantified value and/or a change in the quantified value over time with a predetermined threshold to determine whether a disease has regressed or progressed.
  • the accurate positioning and/or repositioning of the volume of interest and/or shim volume as performed by the MRS voxel planner 14 enables accurate and reproducible quantification of biochemical composition, development of biochemical biomarkers from MRI image data for certain diseases as the biochemical composition for a disease will generally be the same across patients, development of a database of reference data based on MRI image data for known "normal" patients and known “diseased” patients, and/or extraction/query of information from a segmentation using the normative dataset.
  • the functions of the MRS analyzer 16 can be implemented via a processor executing one or more computer readable instructions encoded or embedded on a non-transitory computer readable storage medium such as physical memory.
  • the reference data memory 18 can be used to store results of MRS analysis, including the quantified biochemical composition information, the change in quantified biochemical composition information, the results of the comparison of the quantified biochemical composition information, the results of the comparison of the change in quantified biochemical composition information, the biochemical biomarkers, the database of normative and abnormal reference data, and/or other information.
  • the output device 20 can be used to visually display, transfer and/or otherwise disseminate the information.
  • the output device 20 may include a display monitor, portable memory, a printer, and/or other output device.
  • FIG. 2A illustrates an embodiment of an example computing device 40 that includes functionality of certain embodiments of an MRS voxel planning system.
  • the computing device 40 performs functionality of one or more of the components of the MRI system 10 depicted in FIG. 1. It should be appreciated by one having ordinary skill in the art, in the context of the present disclosure, that some embodiments may have fewer, additional or different components.
  • the computing device 40 may be embodied as an application server, computer, among other computing devices.
  • the example computing device 40 is merely illustrative of one embodiment, and that some embodiments of computing devices may comprise fewer or additional components, and/or some of the functionality associated with the various components depicted in FIG.
  • the computing device 40 is depicted in this example as a computer system, such as one providing a function of a workstation. It should be appreciated that certain well-known components of computer systems are omitted here to avoid obfuscating relevant features of the computing device 40.
  • the computing device 40 comprises a processing circuit 42 comprising hardware and software components.
  • the processing circuit 42 may comprise additional components or fewer components. For instance, memory may be separate.
  • the processing circuit 42 comprises one or more processors, such as processor 44 (P), input/output (I/O) interface(s) 46 (I/O), and memory 48 (MEM), all coupled to one or more data busses, such as data bus 50 (DBUS).
  • the memory 48 may include one or any combination of volatile memory elements (e.g., random-access memory RAM, such as DRAM, and SRAM, etc.) and nonvolatile memory elements (e.g., ROM, Flash, solid state, EPROM, EEPROM, hard drive, tape, CDROM, etc.).
  • Memory 48 may also be referred to herein as a non-transitory, computer readable storage medium.
  • the memory 48 may store a native operating system (OS), one or more native applications, emulation systems, or emulated applications for any of a variety of operating systems and/or emulated hardware platforms, emulated operating systems, etc.
  • the processing circuit 42 may include, or be coupled to, one or more separate storage devices.
  • the processing circuit 42 is coupled via the I/O interfaces 46 to the reference data memory 18 and the data repository 38.
  • the connection may be via an intermediate network, including a local area network (LAN), or a wide area network (WAN), including for data access to network storage (e.g., via the Internet), including cloud-based storage.
  • the reference data memory 18 and the data repository 38 may be coupled to the processing circuit 42 directly via the data bus 50, or in some
  • the data for the reference data memory 18 and the data repository 38 may be stored in memory 48.
  • the reference data memory 18 and the data repository 38 may be stored in persistent memory (e.g., optical, magnetic, and/or semiconductor memory and associated drives) in some embodiments.
  • the I/O interfaces 46 comprise hardware and/or software to provide one or more interfaces to external storage (e.g., the reference data memory 18 and the data repository 38), as well as to other devices including the MRI scanner 12, and a user interface (Ul) 52.
  • the user interface 52 may comprise any one or a combination of a keyboard, mouse, microphone, display screen, immersive head set, etc., which enable input and/or output (e.g., including by and/or for professionals) involved in the scanning of a subject and/or analysis of the MRI or MRS data.
  • the user interface 52 includes the output devices 20 (FIG. 1 ).
  • the I/O interfaces 46 may comprise any number of interfaces for the input and output of signals (e.g., analog or digital data) for conveyance of information (e.g., data) over various networks and according to various protocols and/or standards.
  • the memory 48 comprises an operating system (OS) and a plurality of software/firmware modules, including the MRS voxel planner 14, MR reconstructor (RCNSTR) 32, and the MRS analyzer (MRS ANLYZ) 16.
  • OS operating system
  • RNNSTR MR reconstructor
  • MRS ANLYZ MRS analyzer
  • the MRS voxel planner 14 outputs at least a signal indicative of the volume of interest positioned in the segmented structure, wherein this signal is provided to the MRS analyzer 16, which processes (e.g., analyzes) the volume of interest and provides an output via the user interface 52.
  • the MR reconstructor 32 and MRS analyzer 16 are described above in conjunction with FIG. 1 , and hence the following discussion is directed primarily to the MRS voxel planner 14.
  • the MRS voxel planner 14 comprises an anatomical model bank (BANK) 54, an image segmenter (SEG) 56, a data router (ROUTE) 58, a structure identifier (ID) 60, a volume of interest generator (GEN) 62, a positioning rules bank (RULES) 64, a chemical shift displacement module (SHIFT) 66, and a shim volume adjust module (SHIM) 68.
  • BANK anatomical model bank
  • SEG image segmenter
  • ROUTE data router
  • ID structure identifier
  • GEN volume of interest generator
  • RULES positioning rules bank
  • SHIFT chemical shift displacement module
  • SHIM shim volume adjust module
  • the image segmenter 56 receives the MRI image data and obtains an anatomical model of interest from an anatomical model bank 54.
  • anatomical model of interest 70 is shown in FIG. 2B.
  • the illustrated model of interest 70 represents a human brain. However, it is to be understood that the model of interest 70 may represent other anatomy (e.g., another biological structure). In addition, there may be more than one brain model, for example, one for infants, one for pediatrics and one for adults.
  • the illustrated model of interest 70 is a surface representation of a shape-constrained deformable brain model. Examples of suitable brain models are described in L. Zagorchev, A. Goshtasby, K. Paulsen, T. McAllister, S. Young, and J.
  • the image segmenter 56 is configured to segment the anatomy represented in the MRI image data based on the anatomy represented in the model of interest 70.
  • this process includes performing an initial registration between the model of interest 70 and the MRI image data, transforming the model of interest 70 to the anatomy in the MRI image data based on a transform (e.g., the Hough transform), performing a parametric adaptation of the model of interest 70 (e.g., pose and/or piecewise), and performing a deformable adaptation of the model of interest 70.
  • a transform e.g., the Hough transform
  • a parametric adaptation of the model of interest 70 e.g., pose and/or piecewise
  • deformable adaptation of the model of interest 70 e.g., pose and/or piecewise
  • the structure identifier 60 identifies one or more segmented structures of the segmented MRI image data. For example, where the input signal includes information identifying the hippocampus, the structure identifier 60 identifies the segmented hippocampus in the segmented MRI image data.
  • a volume of interest generator 62 generates a volume of interest to be positioned with respect to the identified segmented structure.
  • the volume of interest generator 62 generates and positions the volume of interest based on one or more positioning rules of a positioning rules bank 64.
  • the particular positioning rule may be determined based on the information in the input signal (INPUT, from FIG. 1 ) and/or otherwise.
  • One rule may indicate that a rectangular MRS voxel volume of interest be placed completely inside the outer surface boundary of the identified segmented structure.
  • One rule may indicate that a rectangular MRS voxel volume of interest be placed completely inside the outer surface boundary of the identified segmented structure.
  • a rectangular MRS voxel may be positioned completely inside an irregular shaped segmented structure, where the segmented structure may be represented via a mesh, and the MRS voxel is positioned in the mesh using mesh vertices as anchors.
  • the vertices may include eight (8) corners, and the volume of interest is placed to satisfy constraints imposed by the locations of the mesh vertices, dependent upon the particular criteria desired by the user, for example, that the MRS voxel is fully contained within the boundaries of the structure of interest.
  • Another rule may indicate that a square MRS voxel volume of interest be placed X % inside and (1 -X) % outside of the outer surface boundary of the identified segmented structure. Another rule may indicate that a spherical volume of interest be placed completely outside of the surface boundary of the identified segmented structure, but within a predetermined x, y, z coordinate therefrom. Another rule may indicate that an irregular shape volume of interest be placed inside the surface boundary so as to conform to the entire shape of the identified segmented structure or a subportion thereof. Irregular shaped MRS voxels may be defined by masking the volume within a structure of interest. Another rule may indicate a location within the identified segmented structure to place the volume of interest. For example, a rule may indicate whether the volume of interest is placed at the head, middle and/or tail of the segmented structure (e.g., the hippocampus).
  • the volume of interest generator 62 may be trained to position the volume of interest. In this instance, a user initially manually positions a volume of interest. The volume of interest generator 62 may then automatically position a subsequent (same) volume of interest based on the manual placement. The volume of interest generator 62 may then automatically position a next volume of interest based on one or more of the manual placements and previous automatic placement. This process may be repeated one or more times. In addition, the user may modify the position of the volume of interest.
  • the volume of interest generator 62 may receive a manual input (e.g., from a professional/clinician) that it translates to the corresponding position on the identified segmented structure, where no positioning rules are implemented.
  • a manual input e.g., from a professional/clinician
  • the chemical shift displacement module 66 and shim volume adjust module 68 make adjustments in the shift displacement direction and the shim volume orientation/position based on determinations of proximity to a tissue boundary comprising lipid and/or water. Such functionality is used in automatic or manual positioning of the MRS voxel(s) based on operation of the volume of interest generator 62 and are described further below.
  • the data router 58 routes the information in the input signal. For example, information corresponding to the model of interest is routed to the image segmenter 56, information corresponding to the segmented structure is routed to the structure identifier 60, and information corresponding to the positioning rule of interest is routed to the volume of interest generator 62. Variations in the manner or sequence of data routing are contemplated for certain embodiments. For instance, in one embodiment, the date router 58 may also route the indicia indicating the segmented structure to the MRS analyzer 16. With this indicia, the MRS analyzer 16 can automatically obtain suitable reference data from the reference data memory 18 without user interaction.
  • Such reference data can include, for example, biochemical normative data to compare with the biochemical data or change therein determined from the volume of interest.
  • the structure of interest may be identified first, and the image segmenter 56 segments a subset of structure such as only the identified structure from the MRI image data. The volume of interest may then be placed with respect to the segmented structure as described herein.
  • the image segmenter 56 and the anatomical model bank 54 are separate from and not part of the MRS voxel planner 14.
  • FIGS. 3A-3B serve as a background underlying the need for functionality associated with the chemical shift displacement module 66 and shim volume adjust module 68.
  • MRS data is acquired from single or plural cuboidal regions of interest (MRS voxel(s)), whether manually or automatically placed and aligned, based on anatomical images acquired with the magnetic resonance imaging (MRI) scanner 12.
  • MRS localization is achieved using bandwidth limited
  • This process is repeated in all three (3) dimensions to fully localize the MRS voxel in space. That is, the intersection of these three (3) planes defines a cube-shaped voxel as the source of the MR signal.
  • the MRS analyzer 16 uses any one of a multitude of techniques for RF and gradient pulse sequences, including STimulated Echo Acquisition Mode (STEAM) or Point RESolved Spectroscopy (PRESS) for its processing of the MRS voxel.
  • STAM STimulated Echo Acquisition Mode
  • PRESS Point RESolved Spectroscopy
  • multiple MRS voxels may be localized, using any one of a multitude of techniques, including chemical shift imaging (CSI), surface coil localization, or image selected in vivo spectroscopy (ISIS) (where the latter may also be used in single MRS voxel localization).
  • CSI chemical shift imaging
  • ISIS image selected in vivo spectroscopy
  • MRS slice selection for voxel localization in MRS is applied assuming a single proton resonant frequency.
  • MRS is able to resolve different chemicals in the biological structure of interest (e.g., the brain) by the different resonant frequencies of their protons.
  • each resonance frequency actually arises from different positions in space, as illustrated in FIG. 3B. That is, the protons on, for instance, NAA and water resonate at different frequencies, which gives rise to an MR spectrum where there is a displacement in the spatial locations selected for each chemical. This limitation is referred to as chemical shift displacement artifact.
  • the MRS voxel is planned using NAA (e.g., at 2.01 parts per million, ppm) as the reference frequency and the resulting position from which the water signal (e.g., at 4.68 ppm) will arise is neglected, leading to poor suppression of the water signal and increased outer volume signal bleed.
  • NAA e.g., at 2.01 parts per million, ppm
  • the water signal which is greater than 5,000 times stronger than the other signals, should be suppressed to allow detection of the other chemicals.
  • water is unknowingly selected in areas of high water content, such as the ventricles which contain cerebrospinal fluid, it can lead to poor magnetic field shimming. Poor water suppression and magnetic field shimming, as well as increased outer volume signal bleed, are three of the most common sources of reduced MRS data quality that limit the clinical utility of MRS.
  • MRS scans In addition to the lack of control of the chemical shift displacement artifact, the vast majority of MRS scans also do not control the location over which the magnetic field is homogenized, known as shimming. A homogeneous magnetic field inside the MRS voxel is necessary to separate peaks in the MR spectrum. For instance, certain MRI machines in practice may automatically center the shim volume over the MRS voxel. If the MRS voxel is under a predetermined dimension (e.g., 2 centimeters (cm)) in any dimension, the shim volume is increased to 2 cm in that dimension to ensure an adequate amount of data is acquired.
  • a predetermined dimension e.g., 2 centimeters (cm)
  • the MRS voxel may not only be smaller than 2 cm in two dimensions in certain instances, but also very close to the ventricles, which have a very large water content. For instance, assuming an MRS voxel of 1.5 x 1.5 x 3.0 cm 3 , and a shim volume larger in all dimensions, when adjusted to a size of 2.0 x 2.0 x 3.0, the resulting increase in shim volume may result in the inadvertent selection of adjacent areas like the ventricles, where it is more difficult to create a homogeneous magnetic field due to the large differences in tissue microstructure. Thus, without user expertise in shim volume placement, the MRS data may be acquired with a suboptimal shim and thus lower quality and reliability.
  • FIGS. 4A-5B illustrate example functionality of an embodiment of chemical shift displacement module 66 and shim volume adjust module 68.
  • the chemical shift displacement module 66 performs an automated adjustment (e.g., optimization) of chemical shift displacement directions that avoid the artifacts from adjacent lipids and/or water in nearby tissue
  • the shim volume adjust module 68 performs an automated positioning (e.g., optimization) of the shim volume to avoid inadvertent overlap with unintended lipids and/or water due to resizing of the shim volume.
  • the MRS voxel planner 14 utilizes automated tissue segmentation and classification to determine the size and location of plural (e.g., sixteen (16)) brain structures, as well as the total grey matter, white matter, and cerebrospinal fluid areas.
  • the segmentation is fast enough to be performed during MRI scan time, enabling the identification of structures and their locations (e.g., of the ventricles and edges of brain tissue), which is passed to the chemical shift
  • displacement module 66 and shim volume adjust module 68 to automatically change the chemical shift directions and shim volume placement, respectively, depending on the voxel orientation and proximity to these tissue boundaries.
  • the MRS voxel planner 14 enables a user to choose automated MRS voxel placement that uses a set of rules (positioning rules bank 64), or place the MRS voxel manually, where the MRS voxel planner 14 translates the location to the map of brain structures and tissue classes.
  • the chemical shift displacement module 66 determines whether the selected MRS voxel location and size is in close proximity to any relevant tissue boundaries, such as ventricles or the skull. The chemical shift displacement module 66 then causes a switch of any gradient directions (e.g., via signaling to the gradient coils 24, FIG.
  • the MRS voxel planner 14 classifies the anatomical images, in this example, a brain image 72, as white matter 74, grey matter 76, or cerebrospinal fluid 78 in a manner as described above.
  • an NAA indicator box 80 reveals a planned MRS voxel selection for NAA without regard to the chemical shift directions, which as shown, is accidentally set up to shift the water selection (via the water indicator box 82 for water) into the fluid in the ventricles.
  • the system is receiving a signal for water from a location (the ventricles) that is not the intended area or volume of interest.
  • Certain embodiments of a chemical shift displacement module 66 take into account the position of the NAA indicator box 80 planned on NAA relative to the bodies of cerebrospinal fluid, and causes a change the magnetic gradient directions (of the gradient coils 24) to avoid selecting water in the ventricles (e.g., shift the direction from which the water signal arises so that it is opposite the ventricles), as shown in FIG. 4B, where the water indicator box 82 reveals a shifted direction relative to the NAA indicator box 80. That is, an embodiment of chemical shift displacement module 66 effects an appropriate change in chemical shift direction to avoid accidental selection of water in the ventricles.
  • the shim volume adjust module 68 determines if the MRS voxel has been prescribed (either manually or automatically) to be less than a preset dimension (e.g., 2 cm) in any dimension, and then shifts the shim volume away from any relevant tissue boundaries to avoid applying the shim algorithm in areas that result in poor shim, such as the ventricles or skull.
  • FIGS. 5A and 5B show the brain image 72 illustrated in FIGS. 4A- 4B, including the white matter 74, grey matter 76, or cerebrospinal fluid 78.
  • 5A demonstrates conventional (default, which is centered or isotropically oriented) resizing and placement of the shim volume indicated by shim volume indicator box 84 when the MRS voxel planned on NAA indicated by NAA indicator box 80 is smaller than 2 cm in at least a single direction.
  • the resizing according to a default (centered) placement may overlap or be proximal to a location that is unintended (e.g., a ventricle, the skull, or anywhere there is a large magnetic susceptibility difference in tissue/structures), which may give rise to a signal that leaks into and possibly distorts the MR spectrum for the localized MRS voxel.
  • the automatic resizing to at least the preset dimension is used to ensure a sufficient volume for acquiring MRS data, where for a sufficient size MRS voxel, the NAA indicator box 80 coincides with the box for the shim volume.
  • the shim volume adjust module 68 takes into account the position of the MRS voxel as indicated by the NAA indicator box 80 relative to the cerebrospinal fluid space 78 and adjusts the position of the shim volume indicator box 84 over which the shim is calculated.
  • the shim volume indicator box 84 normally defaults to a position that is centered about the MRS voxel for NAA (FIG. 5A), whereas in FIG.
  • the position of the shim volume is offset from the default position to avoid the cerebrospinal fluid space 78. That is, an embodiment of the shim volume adjust module 68 effects an appropriate change in shim volume to avoid shimming over water in the ventricles. As explained above, the change is caused by changing the direction the gradient runs through the shim coils 26 (e.g., if the direction is normally from low-high, left-right, then the shift would be caused by a change to, say, high-low).
  • a user e.g., professional
  • the ability to activate functionality of chemical shift displacement and/or shim volume adjustment may be selectively activated and de-activated.
  • one or more of the chemical shift displacement and/or shim volume adjustment functionality may be default settings (and/or incapable of being selectively activated or deactivated).
  • such functionality is performed in a manner that is transparent to a user.
  • one or more of the chemical shift displacement and/or shim volume adjustment functionality may be implemented without immediate visual feedback to the user, including for entry into a data structure (e.g., for research or historical record purposes) and/or for use in other processes.
  • Certain embodiments of an automated pixel planning system reduce the dependence on local user expertise in MRS voxel planning by enabling automated calculation of the appropriate, in some embodiments even optimal, chemical shift displacement directions and shim volume placement, leading to improved MRS data quality and reliability, and faster MRS voxel planning to reduce overall scan time.
  • certain embodiments of an automated MRS voxel planning system may improve data quality and reliability from every MRS scan, independent of local user expertise, which may lead to better results for clinical decision making as well as more reproducible study outcomes in clinical research and clinical trials across a vast range of neurological diseases and neurodegenerative disorders.
  • Execution of the chemical shift displacement module 66 and shim volume adjust module 68 may be implemented by the processor 44 under the management and/or control of the operating system.
  • the processor 44 may be embodied as a custom-made or commercially available processor, a central processing unit (CPU) or an auxiliary processor among several processors, a semiconductor based
  • microprocessor in the form of a microchip
  • macroprocessor a macroprocessor
  • ASICs application specific integrated circuits
  • digital logic gates a plurality of suitably configured digital logic gates, and/or other well-known electrical configurations comprising discrete elements both individually and in various combinations to coordinate the overall operation of the computing device 40.
  • a computer-readable storage medium may comprise an electronic, magnetic, optical, or other physical device or apparatus that may contain or store a computer program (e.g., executable code or instructions) for use by or in connection with a computer-related system or method.
  • the software may be embedded in a variety of computer-readable storage mediums for use by, or in connection with, an instruction execution system, apparatus, or device, such as a computer-based system, processor-containing system, or other system that can fetch the instructions from the instruction execution system, apparatus, or device and execute the instructions.
  • an instruction execution system, apparatus, or device such as a computer-based system, processor-containing system, or other system that can fetch the instructions from the instruction execution system, apparatus, or device and execute the instructions.
  • computing device 40 When certain embodiments of the computing device 40 are implemented at least in part with hardware, such functionality may be implemented with any or a combination of the following technologies, which are known in the art: a discrete logic circuit(s) having logic gates for implementing logic functions upon data signals, an application specific integrated circuit (ASIC) having appropriate combinational logic gates, a programmable gate array(s) (PGA), a field programmable gate array (FPGA), etc.
  • ASIC application specific integrated circuit
  • PGA programmable gate array
  • FPGA field programmable gate array
  • one embodiment of an example automated MRS voxel planning method comprises receiving an indication of placement of at least one MRS voxel on a magnetic resonance image of a biological structure (88); determining whether the MRS voxel placement is proximal to a defined tissue boundary (90); and causing a change in a gradient direction, the change in gradient direction adjusting the placement away from the defined tissue boundary to reduce a chemical shift displacement artifact (92).
  • FIG. 7 illustrates another embodiment of an automated MRS voxel planning method 94, which is shown bounded by a start and end, and comprises receiving an indication of a respective size for all dimensions of at least one magnetic resonance spectroscopy voxel (96), determining a shim volume for the at least one magnetic resonance spectroscopy voxel, the shim volume increased in any dimension that is less than a threshold dimension (98); and responsive to at least a portion of the shim volume being proximal to the defined tissue boundary, causing a position of the shim volume to be adjusted relative to a default position, the adjustment causing the adjusted position of the shim volume to be further from the defined tissue boundary than the default position (100).
  • a threshold dimension 98
  • a claim to a computing device comprising: a memory comprising instructions; and one or more processors configured to execute the instructions to: receive an indication of placement of at least one magnetic resonance spectroscopy voxel on a magnetic resonance image of a biological structure; determine whether the magnetic resonance spectroscopy voxel placement is proximal to a defined tissue boundary; and cause a change in a gradient direction, the change in gradient direction adjusting the placement away from the defined tissue boundary to reduce a chemical shift displacement artifact.
  • the computing device of the prior claim wherein the one or more processors are further configured to execute the instructions to: receive an indication of a respective size for all dimensions of the at least one magnetic resonance spectroscopy voxel; determine a shim volume for the at least one magnetic resonance spectroscopy voxel, the shim volume increased in any dimension that is less than a threshold dimension; and responsive to at least a portion of the shim volume being proximal to the defined tissue boundary, cause a position of the shim volume to be adjusted relative to a default position, the adjustment causing the adjusted position of the shim volume to be further from the defined tissue boundary than the default position.
  • the computing device of any one of the prior claims wherein the one or more processors are further configured to execute the instructions to apply the shim volume according to the adjusted position.
  • the computing device of any one of the prior claims further comprising a display, wherein the one or more processors are further configured to execute the instructions to present the shim volume on the magnetic resonance image according to the adjusted placement.
  • the computing device of any one of the prior claims wherein the biological structure comprises at least a portion of a brain, wherein the one or more processors are further configured to execute the instructions to determine that the defined tissue boundary comprises one of water in or near ventricles or a lipid in or near a skull.
  • the computing device of any one of the prior claims wherein the one or more processors are further configured to execute the instructions to: receive an indication of an additional placement of one or more additional magnetic resonance spectroscopy voxels on a respective location on the imaged biological structure; determine whether the additional placement of the one or more additional magnetic resonance spectroscopy voxels is proximal to the defined tissue boundary; and cause a change in a gradient direction, the change in gradient direction adjusting the additional placement away from the defined tissue boundary.
  • the computing device of any one of the prior claims wherein the one or more processors are further configured to execute the instructions to: receive an indication of a respective size for all dimensions of all of the one or more additional magnetic resonance spectroscopy voxels; determine a shim volume for each of the one or more additional magnetic resonance spectroscopy voxels, the shim volume increased in any dimension that is less than a threshold dimension; and responsive to at least a portion of one or more of the shim volumes for the one or more additional magnetic resonance spectroscopy voxels being proximal to the defined tissue boundary, cause a position of each of the proximal shim volumes to be adjusted relative to a default position, the adjustment causing the adjusted position of the proximal shim volumes to be further from the defined tissue boundary than the default position.
  • the computing device of any one of the prior claims wherein the one or more processors are further configured to execute the instructions to apply the respective shim volumes for the one or more additional magnetic resonance spectroscopy voxels according to the adjusted positions.
  • the computing device of any one of the prior claims wherein the one or more processors are further configured to execute the instructions to process the at least one magnetic resonance spectroscopy voxel and the one or more additional magnetic resonance spectroscopy voxels according to the adjusted placement.
  • the computing device of any one of the prior claims wherein the one or more processors are further configured to execute the instructions to process the at least one magnetic resonance spectroscopy voxel according to the adjusted placement.
  • the computing device of any one of the prior claims further comprising a display, wherein the one or more processors are further configured to execute the instructions to present the magnetic resonance spectroscopy voxel on the display according to the adjusted placement.
  • the computing device of any one of the prior claims wherein the one or more processors are further configured to execute the instructions to receive the indication of placement of the at least one magnetic resonance
  • the computing device of any one of the prior claims further comprising a user interface configured to receive the user input.
  • the computing device of any one of the prior claims wherein the one or more processors are further configured to execute the instructions to identify the biological structure via segmentation of the magnetic resonance image.
  • a claim to a non-transitory, computer readable storage medium comprising executable instructions that, when executed by one or more processors, causes the one or more processors to: receive an indication of placement of at least one magnetic resonance spectroscopy voxel on a magnetic resonance image of a biological structure; determine whether the magnetic resonance spectroscopy voxel placement is proximal to a defined tissue boundary; and cause a change in a gradient direction, the change in gradient direction adjusting the placement away from the defined tissue boundary to reduce a chemical shift displacement artifact.
  • the non-transitory, computer readable storage medium of the prior claim wherein the executable instructions, when executed by the one or more processors, further causes the one or more processors to: receive an indication of a respective size for all dimensions of the at least one magnetic resonance spectroscopy voxel; determine a shim volume for the at least one magnetic resonance spectroscopy voxel, the shim volume increased in any dimension that is less than a threshold dimension; and responsive to at least a portion of the shim volume being proximal to the defined tissue boundary, cause a position of the shim volume to be adjusted relative to a default position, the adjustment causing the adjusted position of the shim volume to be further from the defined tissue boundary than the default position.
  • the non-transitory, computer readable storage medium of any one of the prior non-transitory, computer readable storage medium claims, wherein the executable instructions, when executed by the one or more processors, further causes the one or more processors to apply the shim volume according to the adjusted position.
  • a claim to a magnetic resonance spectroscopy voxel planning method comprising: at one or more processors: receiving an indication of placement of at least one magnetic resonance spectroscopy voxel on a magnetic resonance image of a biological structure; determining whether the magnetic resonance spectroscopy voxel placement is proximal to a defined tissue boundary; and causing a change in a gradient direction, the change in gradient direction adjusting the placement away from the defined tissue boundary to reduce a chemical shift displacement artifact.
  • the magnetic resonance spectroscopy voxel planning method of the prior claim further comprising: receiving an indication of a respective size for all dimensions of the at least one magnetic resonance spectroscopy voxel; determining a shim volume for the at least one magnetic resonance spectroscopy voxel, the shim volume increased in any dimension that is less than a threshold dimension; and responsive to at least a portion of the shim volume being proximal to the defined tissue boundary, cause a position of the shim volume to be adjusted relative to a default position, the adjustment causing the adjusted position of the shim volume to be further from the defined tissue boundary than the default position.
  • a single processor or other unit may fulfill the functions of several items recited in the claims.
  • the mere fact that certain measures are recited in mutually different dependent claims does not indicate that a combination of these measures cannot be used to advantage.
  • a computer program may be stored/distributed on a suitable medium, such as an optical medium or solid-state medium supplied together with or as part of other hardware, but may also be distributed in other forms. Any reference signs in the claims should be not construed as limiting the scope.

Abstract

A computing device that determines whether a magnetic resonance spectroscopy voxel placement is proximal to a defined tissue boundary, and causes a change in a gradient direction, the change in gradient direction adjusting the placement away from the defined tissue boundary.

Description

AUTOMATED VOXEL POSITIONING FOR IN VIVO MAGNETIC RESONANCE
SPECTROSCOPY
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This patent application claims the priority benefit under 35 U.S.C. §
119(e) of U.S. Provisional Application No. 62/825,906 filed on March 29, 2019, the contents of which are herein incorporated by reference
FIELD OF THE INVENTION
[0002] The present invention is generally related to magnetic resonance spectroscopy.
BACKGROUND OF THE INVENTION
[0003] Magnetic resonance imaging (MRI) is a non-invasive imaging technology that produces detailed, three-dimensional anatomical images, such as brain anatomy images, using powerful magnets. A patient is positioned within an MRI machine, and during the imaging process, the magnets are used to produce a strong magnetic field that forces protons in the body to align with the magnetic field. For instance, protons within water nuclei of tissue are usually randomly oriented. The applied magnetic field causes alignment (e.g., magnetization) of the protons, and radio frequency (RF) energy is used to disrupt the alignment. When the protons return to a re-aligned state, RF energy is emitted and measured. The time it takes for the protons to realign with the magnetic field and the amount of RF energy that is emitted is a function of the environment and chemical nature of molecules. This energy exchange, measured as an RF signal, is translated by a computing system into anatomical images by assigning different visual (e.g., gray-scale) levels according to the strength of the emitted signal. In effect, the resulting MRI scans comprise thousands of volume/pixel elements (voxels), which reflect various magnetic properties of the tissues they contain, which a professional (e.g., doctor, including radiologist) interprets to make a diagnosis and prescribe the necessary treatment.
[0004] Magnetic resonance spectroscopy (MRS) provides an additional layer of imaging technology to assist the doctor in enabling a suitable diagnosis/treatment. An MRS system comprises a computing system that uses the MRI image data and various coils of the MRI machine to develop MRS spectra at a given site/volume of interest (e.g., at the voxel level). MRS is the only imaging technique that can assess the levels of a wide range of biologically important chemicals in the human brain both non- invasively and without the use of ionizing radiation. MRS enables detection of many biomarkers of neurological diseases and neurodegenerative disorders, including N- actetylaspartate (NAA), which is involved in myelin synthesis, creatine and phosphocreatine, which are involved in energy storage and mitochondrial function, myo-inositol, which is a marker of glial cell density and gliosis, and glutamate, which is the brain’s primary excitatory neurotransmitter. MRS is able to distinguish between these chemicals, and others, based on the resonant frequencies of their protons. Protons with different local magnetic fields, depending on their chemical neighbors, resonate at different frequencies, leading to a spectrum of proton frequencies detectable in anatomical/biological structures, including the brain.
[0005] However, the quality of MRS data varies widely and is often dependent on local user expertise. These limitations have hampered the development of standardized acquisition protocols and led to poor reliability.
SUMMARY OF THE INVENTION
[0006] One object of the present invention is to provide a magnetic resonance spectroscopy system that mitigates signal artifacts arising from water and/or lipids. To better address such concerns, in a first aspect of the invention, a computing device is disclosed that determines whether magnetic resonance spectroscopy (MRS) voxel placement is proximal to a defined tissue boundary, and causes a change in a gradient direction, the change in gradient direction adjusting the placement of the MRS voxel away from the defined tissue boundary. By adjusting placement away from the tissue boundary, which may include lipid or water that gives rise to artifacts or distortions in a magnetic resonance spectrum, data quality and/or reliability may be improved.
[0007] In one embodiment, the computing device receives an indication of a respective size for all dimensions of the at least one MRS voxel; determines a shim volume for the at least one MRS voxel, the shim volume increased in any dimension that is less than a threshold dimension; and responsive to at least a portion of the shim volume being proximal to the defined tissue boundary, causes a position of the shim volume to be adjusted relative to a default position, the adjustment causing the adjusted position of the shim volume to be further from the defined tissue boundary than the default position. The vast majority of magnetic resonance spectroscopy scans neglect to control a location over which the magnetic field is homogenized, or namely, neglect to perform proper shimming. By controlling the location of the shim volume to avoid tissue having lipid and/or water content that corrupts the spectrum, improvements in data quality and/or reliability may be realized.
[0008] These and other aspects of the invention will be apparent from and elucidated with reference to the embodiment(s) described hereinafter.
BRIEF DESCRIPTION OF THE DRAWINGS
[0009] Many aspects of the invention can be better understood with reference to the following drawings, which are diagrammatic. The components in the drawings are not necessarily to scale, emphasis instead being placed upon clearly illustrating the principles of the present invention. Moreover, in the drawings, like reference numerals designate corresponding parts throughout the several views.
[0010] FIG. 1 is a schematic diagram that illustrates an example environment in which an automated magnetic resonance spectroscopy (MRS) voxel planning system is used, in accordance with an embodiment of the invention.
[0011] FIG. 2A is a block diagram that illustrates an example computing device implementing an automated MRS voxel planning system, in accordance with an embodiment of the invention.
[0012] FIG. 2B is a schematic diagram that illustrates an example brain model.
[0013] FIG. 3A is a block diagram that illustrates a mechanism to access MRS data from a magnetic resonance spectroscopy (MRS) voxel in an automated MRS voxel planning system of FIG. 2A, in accordance with an embodiment of the invention. [0014] FIG. 3B is a schematic diagram that conceptually illustrates magnetic resonance spectroscopy localization, in accordance with an embodiment of the invention.
[0015] FIGS. 4A-4B are block diagrams that illustrate an example change in chemical shift displacement direction implemented by an automated MRS voxel planning system, in accordance with an embodiment of the invention.
[0016] FIGS. 5A-5B are block diagrams that illustrate an example change in shim volume positioning implemented by an automated MRS voxel planning system, in accordance with an embodiment of the invention.
[0017] FIG. 6 is a flow diagram that illustrates an example of an automated MRS voxel planning method, in accordance with an embodiment of the invention.
[0018] FIG. 7 is a flow diagram that illustrates an example of another automated MRS voxel planning method, in accordance with another embodiment of the invention.
DETAILED DESCRIPTION OF EMBODIMENTS
[0019] Disclosed herein are certain embodiments of a magnetic resonance spectroscopy (MRS) voxel planning system and method (collectively hereinafter referred to as an MRS voxel planning system) that automate chemical shift
displacement direction for volumes of interest to be positioned on segmented and categorized structures from magnetic resonance image data. In one embodiment, the MRS voxel planning system determines whether MRS voxel placement is proximal to a defined tissue boundary that comprises lipid and/or water that can reduce the reliability of the MRS data, and causes a change in a gradient direction. The change in gradient direction adjusts the placement of the MRS voxel away from the defined tissue boundary. In some embodiments, the MRS voxel planning system further automates shim volume placement in a manner that is offset from a default position, as set forth in the description below.
[0020] Digressing briefly, current MRS localization techniques often neglect to consider or adequately address chemical shift displacement artifacts in MRS voxel placement. The inadvertent selection of water or lipid content from neighboring tissue, which has a strong signal, may obscure small signals corresponding to a metabolite of interest, resulting in the acquisition of unreliable data. By automating MRS voxel placement, unintended signal contributions from lipid and/or water are avoided, providing for reliable MRS data acquisition and analysis.
[0021] Having summarized certain features of an MRS voxel planning system of the present disclosure, reference will now be made in detail to the description of a MRS voxel planning system as illustrated in the drawings. While an MRS voxel planning system will be described in connection with these drawings, there is no intent to limit it to the embodiment or embodiments disclosed herein. For instance, emphasis is placed on proton-based (1H) MRS, though in some embodiments, other types of nuclei may be used, including phosphor-based MRS. Also, though emphasis in the description below is placed on the use of N-actetylaspartate (NAA) as a biomarker, which is popular for brain analysis, it should be appreciated by one having ordinary skill in the art, in the context of the present disclosure, that other biomarkers may be used for the brain or other biological structures. Additionally, though MRS localization is described in the context of single MRS voxel techniques, multi-MRS voxel techniques may be used and hence are contemplated to be within the scope of the disclosure. Further, although the description identifies or describes specifics of one or more embodiments, such specifics are not necessarily part of every embodiment, nor are all of any various stated advantages necessarily associated with a single embodiment. On the contrary, the intent is to cover all alternatives, modifications and equivalents included within the principles and scope of the disclosure as defined by the appended claims. For instance, two or more embodiments may be interchanged or combined in any combination. Further, it should be appreciated in the context of the present disclosure that the claims are not necessarily limited to the particular embodiments set out in the description.
[0022] Several terms are used in the description that follows that have well- recognized meaning within the magnetic resonance spectroscopy industry, and are referenced briefly below before proceeding with a description of the drawings. An MRS voxel refers to a single, cuboidal region of interest for purposes of acquiring MRS data, and is either manually placed or automatically placed onto a segmented and categorized anatomical or biological image acquired by magnetic resonance imaging. Chemical shift displacement refers to a difference in resonance frequencies of two otherwise identical nuclei present in different molecular environments that gives rise to a displacement in spatial locations for each chemical. For instance, the molecular environment of 1H protons of fat, nestled within long-chain triglycerides, is different than the molecular environment of 1H protons of water, which leads to a difference in spatial locations along, for instance, a magnetic resonance spectrum. More specifically, the spatial position of a localized MRS volume element (e.g., an MRS voxel) obtained by a localization method that employs frequency selective radio frequency (RF) pulses in the presence of magnetic field gradients is linearly affected by the chemical shift of the compound under investigation. A difference in Larmor frequency between two different compounds results in a spatial displacement of the localized volume for one compound relative to the other. A chemical shift displacement artifact comprises a condition where the chemical shift displacement for two or more substances that interface or are in close proximity to one another causes a mismapping or misregistration of a given chemical under investigation, since the chemical under investigation may be obscured by the signal contribution from content (e.g., water, lipids, etc.) from an unintended spatial location. Shimming is also described herein, and in effect, comprises a volume (shim volume) over which the magnetic field is homogenized, where one of plural techniques may be used, including pencil beam shimming, among others.
[0023] Referring now to FIG. 1 , shown is an example environment in which an embodiment of an MRS voxel planning system is used, the environment comprising a magnetic resonance imaging (MRI) system 10. Note that the MRI system 10 illustrated in FIG. 1 is merely illustrative of one example environment, and that in some
embodiments, fewer, more, and/or different components may be used to implement an embodiment of an MRS voxel planning system. In one embodiment, the MRI system 10 includes an MRI scanner 12, an MRS voxel planner 14, and an MRS analyzer 16, which is shown in communication with reference data memory 18 and one or more output devices (output device(s)) 20. The MRI scanner 12 includes a main magnet 22, gradient (x, y and/or z) coils 24, shim coils 26, and an RF coil 28. In some
embodiments, the gradient coils 24 may also be tasked as shim coils 26 (e.g., for first order or linear shimming). The main magnet 22 (which can be a superconducting, resistive, permanent, or other type of magnet) produces a substantially homogeneous, temporally constant main magnetic field B0 in an examination region 30.
[0024] The gradient coils 24 generate time varying gradient magnetic fields along the x, y and/or z-axes of the examination region 30. In one embodiment, the MRS voxel planning system changes the gradient direction to avoid undesired lipid and/or water at or near a tissue boundary.
[0025] The shim coils 26 are used to control magnetic field homogeneity over a given region of interest, including an MRS voxel, where a homogenous magnetic field is necessary to separate peaks in an MR spectrum. In particular, the shim coils 26 are used in vivo to perform a process referred to as shimming to ensure that the B0 magnetic field is homogenous, enabling narrower spectral lines (e.g., improved spectral resolution) from which reliable separation and quantification of chemicals can be achieved. The shim coils 26 are generally comprised of multiple current loops connected in series and placed geometrically so that the magnetic field generated by them across a diameter spherical volume corresponds to a specific spherical harmonic. In embodiments where functionality of the shim coils 26 is performed by the gradient coils 24, the shim coil functionality corresponds to lower order spherical harmonics (e.g., X, Y, and Z shims) in cooperation with a standard gradient amplifier, applied as an offset to the gradient coils 24. All other higher order shim fields may be generated by the shim coils 26 using corresponding shim amplifiers. Software in the MRS voxel planner 14 (or in the MRS analyzer 16 in some embodiments) control shimming based on received measures of magnetic field inhomogeneity to analytically determine the required shim currents. Further, such software (or additional software) of the MRS voxel planner 14 is used to control a volume size adjustment and placement of a shim volume, as described below. In effect, shimming (e.g., in vivo, active shimming) comprises a minimization procedure in which there is an attempt to cancel the measured magnetic field (e.g., based on magnetic field maps) with the available spherical harmonic shims.
[0026] The RF coil 28 includes a transmission portion that transmits a radio frequency signal (e.g., at the Larmor frequency of nuclei of interest such as hydrogen, Helium, etc.) that excites the nuclei of interest in the examination region 30 and a receive portion that receives MR signals emitted by excited nuclei. The transmission and receive portions can alternatively be located in separate coils. An MR reconstructor 32 reconstructs the MR signals and generates MRI image data. A subject support 34 supports a subject such as a human or animal patient in the examination region 30. A general purpose computing system serves as an operator console 36 and includes an output device such as a display and an input device such as a keyboard, mouse, and/or the like. Software resident on the console 36 allows the operator to interact with the scanner 12, for example, to select an imaging protocol, to initiate scanning, etc.
[0027] A data repository 38 can be used to store the image data generated by the scanner 12 and/or other image data. The illustrated data repository 38 may include one or more of a picture archiving and communication system (PACS), a radiology information system (RIS), a hospital information system (HIS), an electronic medical record (EMR) database, a server, a computer, and/or other data repository. The data repository 38 can be local to the MRI system 10 or remote from the system 10.
[0028] The MRS voxel planner 14 is configured to automatically position a volume of interest, such as one or more MRS voxels, with respect to a (biological) structure segmented in MRI image data obtained from the scanner 12, the repository 38 and/or other source. The automatic positioning includes adjustments in chemical shift direction and/or shim volume sizing and/or placement depending on the MRS voxel orientation and proximity to tissue boundaries possessing lipid and/or water. In some embodiments, the MRS voxel planner 14 is configured to operate in conjunction with manual positioning of MRS voxels, including automatic adjustments in the chemical shift direction and/or shim volume placement when the manual positioning is
inadvertently at or near tissue boundaries comprising undesired lipids and/or water.
The illustrated MRS voxel planner 14 receives an input signal, which can include indicia indicating an anatomical model of interest, particular segmented structure, a positioning rule of interest, and/or other information. As described further below, in one instance, the MRS voxel planner 14 utilizes this input to accurately and reproducibly position a volume of interest with respect to segmented structures in the MRI image data for subsequent (localized) MRS scanning and analysis and/or adjust a manual positioning of the volume of interest. The MRS voxel planner 14 also resizes and adjusts the positioning of a shim volume to avoid undesired tissue components (e.g., lipids or water). It is to be appreciated that the functions of the MRS voxel planner 14 can be implemented via a computing device having one or more processors executing one or more computer readable instructions encoded or embedded on a non-transitory, computer readable storage medium, including physical memory. In one embodiment, the MRS voxel planner 14 may reside in the console 36. In some embodiments, the MRS voxel planner 14 may reside external to the console 36 (e.g., at a remote computing device (e.g., a server) or at a local computing device (e.g., local server and/or workstation, laptop, etc.).
[0029] The MRS analyzer 16 analyzes the volume of interest based on the positioning of the MRS voxel planner 14. This includes performing magnetic resonance spectroscopy to quantify biochemical composition in the volume of interest with respect to the segmented structure and/or comparing the quantified value and/or a change in the quantified value over time with a predetermined threshold to determine whether a disease has regressed or progressed. The accurate positioning and/or repositioning of the volume of interest and/or shim volume as performed by the MRS voxel planner 14 enables accurate and reproducible quantification of biochemical composition, development of biochemical biomarkers from MRI image data for certain diseases as the biochemical composition for a disease will generally be the same across patients, development of a database of reference data based on MRI image data for known "normal" patients and known "diseased" patients, and/or extraction/query of information from a segmentation using the normative dataset. It is to be appreciated that the functions of the MRS analyzer 16 can be implemented via a processor executing one or more computer readable instructions encoded or embedded on a non-transitory computer readable storage medium such as physical memory.
[0030] The reference data memory 18 can be used to store results of MRS analysis, including the quantified biochemical composition information, the change in quantified biochemical composition information, the results of the comparison of the quantified biochemical composition information, the results of the comparison of the change in quantified biochemical composition information, the biochemical biomarkers, the database of normative and abnormal reference data, and/or other information. The output device 20 can be used to visually display, transfer and/or otherwise disseminate the information. The output device 20 may include a display monitor, portable memory, a printer, and/or other output device.
[0031] FIG. 2A illustrates an embodiment of an example computing device 40 that includes functionality of certain embodiments of an MRS voxel planning system. In one embodiment, the computing device 40 performs functionality of one or more of the components of the MRI system 10 depicted in FIG. 1. It should be appreciated by one having ordinary skill in the art, in the context of the present disclosure, that some embodiments may have fewer, additional or different components. The computing device 40 may be embodied as an application server, computer, among other computing devices. One having ordinary skill in the art should appreciate in the context of the present disclosure that the example computing device 40 is merely illustrative of one embodiment, and that some embodiments of computing devices may comprise fewer or additional components, and/or some of the functionality associated with the various components depicted in FIG. 2A may be combined, or further distributed among additional modules or computing devices, in some embodiments. The computing device 40 is depicted in this example as a computer system, such as one providing a function of a workstation. It should be appreciated that certain well-known components of computer systems are omitted here to avoid obfuscating relevant features of the computing device 40. In one embodiment, the computing device 40 comprises a processing circuit 42 comprising hardware and software components. In some embodiments, the processing circuit 42 may comprise additional components or fewer components. For instance, memory may be separate. The processing circuit 42 comprises one or more processors, such as processor 44 (P), input/output (I/O) interface(s) 46 (I/O), and memory 48 (MEM), all coupled to one or more data busses, such as data bus 50 (DBUS). The memory 48 may include one or any combination of volatile memory elements (e.g., random-access memory RAM, such as DRAM, and SRAM, etc.) and nonvolatile memory elements (e.g., ROM, Flash, solid state, EPROM, EEPROM, hard drive, tape, CDROM, etc.). Memory 48 may also be referred to herein as a non-transitory, computer readable storage medium.
[0032] The memory 48 may store a native operating system (OS), one or more native applications, emulation systems, or emulated applications for any of a variety of operating systems and/or emulated hardware platforms, emulated operating systems, etc. In some embodiments, the processing circuit 42 may include, or be coupled to, one or more separate storage devices. For instance, in the depicted embodiment, the processing circuit 42 is coupled via the I/O interfaces 46 to the reference data memory 18 and the data repository 38. The connection may be via an intermediate network, including a local area network (LAN), or a wide area network (WAN), including for data access to network storage (e.g., via the Internet), including cloud-based storage. In some embodiments, the reference data memory 18 and the data repository 38 may be coupled to the processing circuit 42 directly via the data bus 50, or in some
embodiments, the data for the reference data memory 18 and the data repository 38 may be stored in memory 48. The reference data memory 18 and the data repository 38 may be stored in persistent memory (e.g., optical, magnetic, and/or semiconductor memory and associated drives) in some embodiments.
[0033] The I/O interfaces 46 comprise hardware and/or software to provide one or more interfaces to external storage (e.g., the reference data memory 18 and the data repository 38), as well as to other devices including the MRI scanner 12, and a user interface (Ul) 52. The user interface 52 may comprise any one or a combination of a keyboard, mouse, microphone, display screen, immersive head set, etc., which enable input and/or output (e.g., including by and/or for professionals) involved in the scanning of a subject and/or analysis of the MRI or MRS data. In one embodiment, the user interface 52 includes the output devices 20 (FIG. 1 ). The I/O interfaces 46 may comprise any number of interfaces for the input and output of signals (e.g., analog or digital data) for conveyance of information (e.g., data) over various networks and according to various protocols and/or standards.
[0034] In the embodiment depicted in FIG. 2A, the memory 48 comprises an operating system (OS) and a plurality of software/firmware modules, including the MRS voxel planner 14, MR reconstructor (RCNSTR) 32, and the MRS analyzer (MRS ANLYZ) 16. In some embodiments, the functionality of two or more of the modules may be combined, or distributed among additional modules in the same or plural devices. The MRS voxel planner 14 outputs at least a signal indicative of the volume of interest positioned in the segmented structure, wherein this signal is provided to the MRS analyzer 16, which processes (e.g., analyzes) the volume of interest and provides an output via the user interface 52. The MR reconstructor 32 and MRS analyzer 16 are described above in conjunction with FIG. 1 , and hence the following discussion is directed primarily to the MRS voxel planner 14. The MRS voxel planner 14 comprises an anatomical model bank (BANK) 54, an image segmenter (SEG) 56, a data router (ROUTE) 58, a structure identifier (ID) 60, a volume of interest generator (GEN) 62, a positioning rules bank (RULES) 64, a chemical shift displacement module (SHIFT) 66, and a shim volume adjust module (SHIM) 68.
[0035] The image segmenter 56 receives the MRI image data and obtains an anatomical model of interest from an anatomical model bank 54. An example
anatomical model of interest 70 is shown in FIG. 2B. The illustrated model of interest 70 represents a human brain. However, it is to be understood that the model of interest 70 may represent other anatomy (e.g., another biological structure). In addition, there may be more than one brain model, for example, one for infants, one for pediatrics and one for adults. The illustrated model of interest 70 is a surface representation of a shape-constrained deformable brain model. Examples of suitable brain models are described in L. Zagorchev, A. Goshtasby, K. Paulsen, T. McAllister, S. Young, and J. Weese, Manual annotation, 3-D shape reconstruction, and traumatic brain injury analysis, Int'l Workshop Multimodal Brain Image Analysis (MBIA), Toronto, Calif., September 2011 , and L. Zagorchev, C. Meyer, T. Stehle, R. Kneser, S. Young, and J. Weese, Evaluation of Traumatic Brain Injury patients using a shape-constrained deformable model, Int'l Workshop Multimodal Brain Image Analysis (MBIA), Toronto, Calif., September 2011. Other models are also contemplated herein.
[0036] The image segmenter 56 is configured to segment the anatomy represented in the MRI image data based on the anatomy represented in the model of interest 70. In one non-limiting instance, this process includes performing an initial registration between the model of interest 70 and the MRI image data, transforming the model of interest 70 to the anatomy in the MRI image data based on a transform (e.g., the Hough transform), performing a parametric adaptation of the model of interest 70 (e.g., pose and/or piecewise), and performing a deformable adaptation of the model of interest 70. Other known techniques can alternatively be used.
[0037] The structure identifier 60 identifies one or more segmented structures of the segmented MRI image data. For example, where the input signal includes information identifying the hippocampus, the structure identifier 60 identifies the segmented hippocampus in the segmented MRI image data.
[0038] A volume of interest generator 62 generates a volume of interest to be positioned with respect to the identified segmented structure. In one embodiment, the volume of interest generator 62 generates and positions the volume of interest based on one or more positioning rules of a positioning rules bank 64. The particular positioning rule may be determined based on the information in the input signal (INPUT, from FIG. 1 ) and/or otherwise. One rule may indicate that a rectangular MRS voxel volume of interest be placed completely inside the outer surface boundary of the identified segmented structure. One rule may indicate that a rectangular MRS voxel volume of interest be placed completely inside the outer surface boundary of the identified segmented structure. For instance, a rectangular MRS voxel may be positioned completely inside an irregular shaped segmented structure, where the segmented structure may be represented via a mesh, and the MRS voxel is positioned in the mesh using mesh vertices as anchors. For a rectangular MRS voxel, the vertices may include eight (8) corners, and the volume of interest is placed to satisfy constraints imposed by the locations of the mesh vertices, dependent upon the particular criteria desired by the user, for example, that the MRS voxel is fully contained within the boundaries of the structure of interest. Another rule may indicate that a square MRS voxel volume of interest be placed X % inside and (1 -X) % outside of the outer surface boundary of the identified segmented structure. Another rule may indicate that a spherical volume of interest be placed completely outside of the surface boundary of the identified segmented structure, but within a predetermined x, y, z coordinate therefrom. Another rule may indicate that an irregular shape volume of interest be placed inside the surface boundary so as to conform to the entire shape of the identified segmented structure or a subportion thereof. Irregular shaped MRS voxels may be defined by masking the volume within a structure of interest. Another rule may indicate a location within the identified segmented structure to place the volume of interest. For example, a rule may indicate whether the volume of interest is placed at the head, middle and/or tail of the segmented structure (e.g., the hippocampus).
Another rule may indicate the positioning of multiple volumes of interest. Other rules are also contemplated herein. In one embodiment, the volume of interest generator 62 may be trained to position the volume of interest. In this instance, a user initially manually positions a volume of interest. The volume of interest generator 62 may then automatically position a subsequent (same) volume of interest based on the manual placement. The volume of interest generator 62 may then automatically position a next volume of interest based on one or more of the manual placements and previous automatic placement. This process may be repeated one or more times. In addition, the user may modify the position of the volume of interest.
[0039] In some embodiments, the volume of interest generator 62 may receive a manual input (e.g., from a professional/clinician) that it translates to the corresponding position on the identified segmented structure, where no positioning rules are implemented.
[0040] The chemical shift displacement module 66 and shim volume adjust module 68 make adjustments in the shift displacement direction and the shim volume orientation/position based on determinations of proximity to a tissue boundary comprising lipid and/or water. Such functionality is used in automatic or manual positioning of the MRS voxel(s) based on operation of the volume of interest generator 62 and are described further below.
[0041] The data router 58 routes the information in the input signal. For example, information corresponding to the model of interest is routed to the image segmenter 56, information corresponding to the segmented structure is routed to the structure identifier 60, and information corresponding to the positioning rule of interest is routed to the volume of interest generator 62. Variations in the manner or sequence of data routing are contemplated for certain embodiments. For instance, in one embodiment, the date router 58 may also route the indicia indicating the segmented structure to the MRS analyzer 16. With this indicia, the MRS analyzer 16 can automatically obtain suitable reference data from the reference data memory 18 without user interaction. Such reference data can include, for example, biochemical normative data to compare with the biochemical data or change therein determined from the volume of interest. In some embodiments, the structure of interest may be identified first, and the image segmenter 56 segments a subset of structure such as only the identified structure from the MRI image data. The volume of interest may then be placed with respect to the segmented structure as described herein. In some embodiments, the image segmenter 56 and the anatomical model bank 54 are separate from and not part of the MRS voxel planner 14.
[0042] Before describing the functionality of the chemical shift displacement module 66 and shim volume adjust module 68, attention is directed to FIGS. 3A-3B, which serve as a background underlying the need for functionality associated with the chemical shift displacement module 66 and shim volume adjust module 68. From the description above, it is evident that MRS data is acquired from single or plural cuboidal regions of interest (MRS voxel(s)), whether manually or automatically placed and aligned, based on anatomical images acquired with the magnetic resonance imaging (MRI) scanner 12. MRS localization is achieved using bandwidth limited
radiofrequency (RF) pulses via the RF coils 28 combined with magnetic field gradients via the gradient coils 24 to create a certain slice thickness in one spatial dimension, as illustrated in FIG. 3A. That is, shown is a one dimensional MRS localization by slice selection, wherein the MRS voxel is spatially defined in one dimension (Dc) by the bandwidth (Dί) of the RF pulse combined with the strength (Gx) of the magnetic field gradient for that dimension. This process is repeated in all three (3) dimensions to fully localize the MRS voxel in space. That is, the intersection of these three (3) planes defines a cube-shaped voxel as the source of the MR signal. Note that, for an embodiment of the chemical shift displacement module 66, a change in the gradient direction changes the slope of Gx, which alters the direction from which the water signal arises relative to the signal for NAA, as explained further below. For single voxel localization, the MRS analyzer 16 uses any one of a multitude of techniques for RF and gradient pulse sequences, including STimulated Echo Acquisition Mode (STEAM) or Point RESolved Spectroscopy (PRESS) for its processing of the MRS voxel. In some embodiments, multiple MRS voxels may be localized, using any one of a multitude of techniques, including chemical shift imaging (CSI), surface coil localization, or image selected in vivo spectroscopy (ISIS) (where the latter may also be used in single MRS voxel localization).
[0043] Slice selection for voxel localization in MRS is applied assuming a single proton resonant frequency. Flowever, MRS is able to resolve different chemicals in the biological structure of interest (e.g., the brain) by the different resonant frequencies of their protons. Thus, each resonance frequency actually arises from different positions in space, as illustrated in FIG. 3B. That is, the protons on, for instance, NAA and water resonate at different frequencies, which gives rise to an MR spectrum where there is a displacement in the spatial locations selected for each chemical. This limitation is referred to as chemical shift displacement artifact.
[0044] As explained above, in the vast majority of MRS scans, the chemical shift displacement artifact is not taken into account. For instance, the MRS voxel is planned using NAA (e.g., at 2.01 parts per million, ppm) as the reference frequency and the resulting position from which the water signal (e.g., at 4.68 ppm) will arise is neglected, leading to poor suppression of the water signal and increased outer volume signal bleed. The water signal, which is greater than 5,000 times stronger than the other signals, should be suppressed to allow detection of the other chemicals. In addition, if water is unknowingly selected in areas of high water content, such as the ventricles which contain cerebrospinal fluid, it can lead to poor magnetic field shimming. Poor water suppression and magnetic field shimming, as well as increased outer volume signal bleed, are three of the most common sources of reduced MRS data quality that limit the clinical utility of MRS.
[0045] In addition to the lack of control of the chemical shift displacement artifact, the vast majority of MRS scans also do not control the location over which the magnetic field is homogenized, known as shimming. A homogeneous magnetic field inside the MRS voxel is necessary to separate peaks in the MR spectrum. For instance, certain MRI machines in practice may automatically center the shim volume over the MRS voxel. If the MRS voxel is under a predetermined dimension (e.g., 2 centimeters (cm)) in any dimension, the shim volume is increased to 2 cm in that dimension to ensure an adequate amount of data is acquired. However, in many anatomically interesting regions, such as the hippocampus, the MRS voxel may not only be smaller than 2 cm in two dimensions in certain instances, but also very close to the ventricles, which have a very large water content. For instance, assuming an MRS voxel of 1.5 x 1.5 x 3.0 cm3, and a shim volume larger in all dimensions, when adjusted to a size of 2.0 x 2.0 x 3.0, the resulting increase in shim volume may result in the inadvertent selection of adjacent areas like the ventricles, where it is more difficult to create a homogeneous magnetic field due to the large differences in tissue microstructure. Thus, without user expertise in shim volume placement, the MRS data may be acquired with a suboptimal shim and thus lower quality and reliability.
[0046] Having described certain conditions that illustrate the need for
adjustments in chemical shift displacement direction and/or shim volume positioning, attention is now directed to FIGS. 4A-5B to illustrate example functionality of an embodiment of chemical shift displacement module 66 and shim volume adjust module 68. In particular, the chemical shift displacement module 66 performs an automated adjustment (e.g., optimization) of chemical shift displacement directions that avoid the artifacts from adjacent lipids and/or water in nearby tissue, and the shim volume adjust module 68 performs an automated positioning (e.g., optimization) of the shim volume to avoid inadvertent overlap with unintended lipids and/or water due to resizing of the shim volume. As described above, the MRS voxel planner 14 utilizes automated tissue segmentation and classification to determine the size and location of plural (e.g., sixteen (16)) brain structures, as well as the total grey matter, white matter, and cerebrospinal fluid areas. The segmentation is fast enough to be performed during MRI scan time, enabling the identification of structures and their locations (e.g., of the ventricles and edges of brain tissue), which is passed to the chemical shift
displacement module 66 and shim volume adjust module 68 to automatically change the chemical shift directions and shim volume placement, respectively, depending on the voxel orientation and proximity to these tissue boundaries.
[0047] Once the brain images have been segmented, the MRS voxel planner 14 enables a user to choose automated MRS voxel placement that uses a set of rules (positioning rules bank 64), or place the MRS voxel manually, where the MRS voxel planner 14 translates the location to the map of brain structures and tissue classes. In one embodiment, the chemical shift displacement module 66 determines whether the selected MRS voxel location and size is in close proximity to any relevant tissue boundaries, such as ventricles or the skull. The chemical shift displacement module 66 then causes a switch of any gradient directions (e.g., via signaling to the gradient coils 24, FIG. 1 ) in which the chemical shift displacement would lead to selection of water in or near ventricles, or selection of lipid(s) in or near the skull, to avoid accidental selection of these problematic outer volume signals. For instance, and referring to FIGS. 4A-4B, the MRS voxel planner 14 classifies the anatomical images, in this example, a brain image 72, as white matter 74, grey matter 76, or cerebrospinal fluid 78 in a manner as described above. In FIG. 4A, an NAA indicator box 80 reveals a planned MRS voxel selection for NAA without regard to the chemical shift directions, which as shown, is accidentally set up to shift the water selection (via the water indicator box 82 for water) into the fluid in the ventricles. In this instance, the system is receiving a signal for water from a location (the ventricles) that is not the intended area or volume of interest. Certain embodiments of a chemical shift displacement module 66 take into account the position of the NAA indicator box 80 planned on NAA relative to the bodies of cerebrospinal fluid, and causes a change the magnetic gradient directions (of the gradient coils 24) to avoid selecting water in the ventricles (e.g., shift the direction from which the water signal arises so that it is opposite the ventricles), as shown in FIG. 4B, where the water indicator box 82 reveals a shifted direction relative to the NAA indicator box 80. That is, an embodiment of chemical shift displacement module 66 effects an appropriate change in chemical shift direction to avoid accidental selection of water in the ventricles.
[0048] Referring now to the shim volume adjust module 68, in one embodiment, the shim volume adjust module 68 determines if the MRS voxel has been prescribed (either manually or automatically) to be less than a preset dimension (e.g., 2 cm) in any dimension, and then shifts the shim volume away from any relevant tissue boundaries to avoid applying the shim algorithm in areas that result in poor shim, such as the ventricles or skull. FIGS. 5A and 5B show the brain image 72 illustrated in FIGS. 4A- 4B, including the white matter 74, grey matter 76, or cerebrospinal fluid 78. FIG. 5A demonstrates conventional (default, which is centered or isotropically oriented) resizing and placement of the shim volume indicated by shim volume indicator box 84 when the MRS voxel planned on NAA indicated by NAA indicator box 80 is smaller than 2 cm in at least a single direction. The resizing according to a default (centered) placement may overlap or be proximal to a location that is unintended (e.g., a ventricle, the skull, or anywhere there is a large magnetic susceptibility difference in tissue/structures), which may give rise to a signal that leaks into and possibly distorts the MR spectrum for the localized MRS voxel. Note that the automatic resizing to at least the preset dimension is used to ensure a sufficient volume for acquiring MRS data, where for a sufficient size MRS voxel, the NAA indicator box 80 coincides with the box for the shim volume. Referring to FIG. 5B, certain embodiments of the shim volume adjust module 68 takes into account the position of the MRS voxel as indicated by the NAA indicator box 80 relative to the cerebrospinal fluid space 78 and adjusts the position of the shim volume indicator box 84 over which the shim is calculated. In particular, the shim volume indicator box 84 normally defaults to a position that is centered about the MRS voxel for NAA (FIG. 5A), whereas in FIG. 5B, the position of the shim volume is offset from the default position to avoid the cerebrospinal fluid space 78. That is, an embodiment of the shim volume adjust module 68 effects an appropriate change in shim volume to avoid shimming over water in the ventricles. As explained above, the change is caused by changing the direction the gradient runs through the shim coils 26 (e.g., if the direction is normally from low-high, left-right, then the shift would be caused by a change to, say, high-low).
[0049] Note that certain embodiments are described wherein a user (e.g., professional) is presented with the ability to activate functionality of chemical shift displacement and/or shim volume adjustment. In some embodiments, one or more of these functions may be selectively activated and de-activated. In some embodiments, one or more of the chemical shift displacement and/or shim volume adjustment functionality may be default settings (and/or incapable of being selectively activated or deactivated). In some embodiments, such functionality is performed in a manner that is transparent to a user. For instance, one or more of the chemical shift displacement and/or shim volume adjustment functionality may be implemented without immediate visual feedback to the user, including for entry into a data structure (e.g., for research or historical record purposes) and/or for use in other processes.
[0050] Certain embodiments of an automated pixel planning system reduce the dependence on local user expertise in MRS voxel planning by enabling automated calculation of the appropriate, in some embodiments even optimal, chemical shift displacement directions and shim volume placement, leading to improved MRS data quality and reliability, and faster MRS voxel planning to reduce overall scan time. In other words, certain embodiments of an automated MRS voxel planning system may improve data quality and reliability from every MRS scan, independent of local user expertise, which may lead to better results for clinical decision making as well as more reproducible study outcomes in clinical research and clinical trials across a vast range of neurological diseases and neurodegenerative disorders.
[0051] Execution of the chemical shift displacement module 66 and shim volume adjust module 68 may be implemented by the processor 44 under the management and/or control of the operating system. The processor 44 may be embodied as a custom-made or commercially available processor, a central processing unit (CPU) or an auxiliary processor among several processors, a semiconductor based
microprocessor (in the form of a microchip), a macroprocessor, one or more application specific integrated circuits (ASICs), a plurality of suitably configured digital logic gates, and/or other well-known electrical configurations comprising discrete elements both individually and in various combinations to coordinate the overall operation of the computing device 40.
[0052] When certain embodiments of the computing device 40 are implemented at least in part with software (including firmware), as depicted in FIG. 2A, it should be noted that the software can be stored on a variety of non-transitory computer-readable storage medium for use by, or in connection with, a variety of computer-related systems or methods. In the context of this document, a computer-readable storage medium may comprise an electronic, magnetic, optical, or other physical device or apparatus that may contain or store a computer program (e.g., executable code or instructions) for use by or in connection with a computer-related system or method. The software may be embedded in a variety of computer-readable storage mediums for use by, or in connection with, an instruction execution system, apparatus, or device, such as a computer-based system, processor-containing system, or other system that can fetch the instructions from the instruction execution system, apparatus, or device and execute the instructions.
[0053] When certain embodiments of the computing device 40 are implemented at least in part with hardware, such functionality may be implemented with any or a combination of the following technologies, which are known in the art: a discrete logic circuit(s) having logic gates for implementing logic functions upon data signals, an application specific integrated circuit (ASIC) having appropriate combinational logic gates, a programmable gate array(s) (PGA), a field programmable gate array (FPGA), etc.
[0054] Flaving described certain functionality of the chemical shift displacement module 66 and shim volume adjust module 68, it should be appreciated that one embodiment of an example automated MRS voxel planning method, depicted in FIG. 6 and denoted as method 86, which is shown bounded by a start and end, comprises receiving an indication of placement of at least one MRS voxel on a magnetic resonance image of a biological structure (88); determining whether the MRS voxel placement is proximal to a defined tissue boundary (90); and causing a change in a gradient direction, the change in gradient direction adjusting the placement away from the defined tissue boundary to reduce a chemical shift displacement artifact (92).
[0055] FIG. 7 illustrates another embodiment of an automated MRS voxel planning method 94, which is shown bounded by a start and end, and comprises receiving an indication of a respective size for all dimensions of at least one magnetic resonance spectroscopy voxel (96), determining a shim volume for the at least one magnetic resonance spectroscopy voxel, the shim volume increased in any dimension that is less than a threshold dimension (98); and responsive to at least a portion of the shim volume being proximal to the defined tissue boundary, causing a position of the shim volume to be adjusted relative to a default position, the adjustment causing the adjusted position of the shim volume to be further from the defined tissue boundary than the default position (100).
[0056] Any process descriptions or blocks in flow diagrams should be
understood as representing modules, segments, or portions of code which include one or more executable instructions for implementing specific logical functions or steps in the process, and alternate implementations are included within the scope of the embodiments in which functions may be executed out of order from that shown or discussed, including substantially concurrently or in reverse order, depending on the functionality involved, as would be understood by those reasonably skilled in the art of the present disclosure. In some embodiments, one or more steps may be omitted, or further steps may be added.
[0057] In one embodiment, a claim to a computing device, comprising: a memory comprising instructions; and one or more processors configured to execute the instructions to: receive an indication of placement of at least one magnetic resonance spectroscopy voxel on a magnetic resonance image of a biological structure; determine whether the magnetic resonance spectroscopy voxel placement is proximal to a defined tissue boundary; and cause a change in a gradient direction, the change in gradient direction adjusting the placement away from the defined tissue boundary to reduce a chemical shift displacement artifact.
[0058] In one embodiment, the computing device of the prior claim, wherein the one or more processors are further configured to execute the instructions to: receive an indication of a respective size for all dimensions of the at least one magnetic resonance spectroscopy voxel; determine a shim volume for the at least one magnetic resonance spectroscopy voxel, the shim volume increased in any dimension that is less than a threshold dimension; and responsive to at least a portion of the shim volume being proximal to the defined tissue boundary, cause a position of the shim volume to be adjusted relative to a default position, the adjustment causing the adjusted position of the shim volume to be further from the defined tissue boundary than the default position.
[0059] In one embodiment, the computing device of any one of the prior claims, wherein the one or more processors are further configured to execute the instructions to apply the shim volume according to the adjusted position.
[0060] In one embodiment, the computing device of any one of the prior claims, further comprising a display, wherein the one or more processors are further configured to execute the instructions to present the shim volume on the magnetic resonance image according to the adjusted placement.
[0061] In one embodiment, the computing device of any one of the prior claims, wherein the biological structure comprises at least a portion of a brain, wherein the one or more processors are further configured to execute the instructions to determine that the defined tissue boundary comprises one of water in or near ventricles or a lipid in or near a skull.
[0062] In one embodiment, the computing device of any one of the prior claims, wherein the one or more processors are further configured to execute the instructions to: receive an indication of an additional placement of one or more additional magnetic resonance spectroscopy voxels on a respective location on the imaged biological structure; determine whether the additional placement of the one or more additional magnetic resonance spectroscopy voxels is proximal to the defined tissue boundary; and cause a change in a gradient direction, the change in gradient direction adjusting the additional placement away from the defined tissue boundary.
[0063] In one embodiment, the computing device of any one of the prior claims, wherein the one or more processors are further configured to execute the instructions to: receive an indication of a respective size for all dimensions of all of the one or more additional magnetic resonance spectroscopy voxels; determine a shim volume for each of the one or more additional magnetic resonance spectroscopy voxels, the shim volume increased in any dimension that is less than a threshold dimension; and responsive to at least a portion of one or more of the shim volumes for the one or more additional magnetic resonance spectroscopy voxels being proximal to the defined tissue boundary, cause a position of each of the proximal shim volumes to be adjusted relative to a default position, the adjustment causing the adjusted position of the proximal shim volumes to be further from the defined tissue boundary than the default position.
[0064] In one embodiment, the computing device of any one of the prior claims, wherein the one or more processors are further configured to execute the instructions to apply the respective shim volumes for the one or more additional magnetic resonance spectroscopy voxels according to the adjusted positions.
[0065] In one embodiment, the computing device of any one of the prior claims, wherein the one or more processors are further configured to execute the instructions to process the at least one magnetic resonance spectroscopy voxel and the one or more additional magnetic resonance spectroscopy voxels according to the adjusted placement.
[0066] In one embodiment, the computing device of any one of the prior claims, wherein the one or more processors are further configured to execute the instructions to process the at least one magnetic resonance spectroscopy voxel according to the adjusted placement. [0067] In one embodiment, the computing device of any one of the prior claims, further comprising a display, wherein the one or more processors are further configured to execute the instructions to present the magnetic resonance spectroscopy voxel on the display according to the adjusted placement.
[0068] In one embodiment, the computing device of any one of the prior claims, wherein the one or more processors are further configured to execute the instructions to receive the indication of placement of the at least one magnetic resonance
spectroscopy voxel on the magnetic resonance image of the biological structure based on user input.
[0069] In one embodiment, the computing device of any one of the prior claims, further comprising a user interface configured to receive the user input.
[0070] In one embodiment, the computing device of any one of the prior claims, wherein the one or more processors are further configured to execute the instructions to identify the biological structure via segmentation of the magnetic resonance image.
[0071] In one embodiment, a claim to a non-transitory, computer readable storage medium comprising executable instructions that, when executed by one or more processors, causes the one or more processors to: receive an indication of placement of at least one magnetic resonance spectroscopy voxel on a magnetic resonance image of a biological structure; determine whether the magnetic resonance spectroscopy voxel placement is proximal to a defined tissue boundary; and cause a change in a gradient direction, the change in gradient direction adjusting the placement away from the defined tissue boundary to reduce a chemical shift displacement artifact.
[0072] In one embodiment, the non-transitory, computer readable storage medium of the prior claim, wherein the executable instructions, when executed by the one or more processors, further causes the one or more processors to: receive an indication of a respective size for all dimensions of the at least one magnetic resonance spectroscopy voxel; determine a shim volume for the at least one magnetic resonance spectroscopy voxel, the shim volume increased in any dimension that is less than a threshold dimension; and responsive to at least a portion of the shim volume being proximal to the defined tissue boundary, cause a position of the shim volume to be adjusted relative to a default position, the adjustment causing the adjusted position of the shim volume to be further from the defined tissue boundary than the default position.
[0073] In one embodiment, the non-transitory, computer readable storage medium of any one of the prior non-transitory, computer readable storage medium claims, wherein the executable instructions, when executed by the one or more processors, further causes the one or more processors to apply the shim volume according to the adjusted position.
[0074] In one embodiment, the non-transitory, computer readable storage medium of any one of the prior non-transitory, computer readable storage medium claims, wherein the biological structure comprises at least a portion of a brain, wherein the executable instructions, when executed by the one or more processors, further causes the one or more processors to determine that the defined tissue boundary comprises one of a water voxel in or near ventricles or a lipid voxel in or near a skull based on the segmented brain images.
[0075] In one embodiment, a claim to a magnetic resonance spectroscopy voxel planning method, the method comprising: at one or more processors: receiving an indication of placement of at least one magnetic resonance spectroscopy voxel on a magnetic resonance image of a biological structure; determining whether the magnetic resonance spectroscopy voxel placement is proximal to a defined tissue boundary; and causing a change in a gradient direction, the change in gradient direction adjusting the placement away from the defined tissue boundary to reduce a chemical shift displacement artifact.
[0076] In one embodiment, the magnetic resonance spectroscopy voxel planning method of the prior claim, further comprising: receiving an indication of a respective size for all dimensions of the at least one magnetic resonance spectroscopy voxel; determining a shim volume for the at least one magnetic resonance spectroscopy voxel, the shim volume increased in any dimension that is less than a threshold dimension; and responsive to at least a portion of the shim volume being proximal to the defined tissue boundary, cause a position of the shim volume to be adjusted relative to a default position, the adjustment causing the adjusted position of the shim volume to be further from the defined tissue boundary than the default position.
[0077] While the invention has been illustrated and described in detail in the drawings and foregoing description, such illustration and description are to be considered illustrative or exemplary and not restrictive; the invention is not limited to the disclosed embodiments. Other variations to the disclosed embodiments can be understood and effected by those skilled in the art in practicing the claimed invention, from a study of the drawings, the disclosure, and the appended claims. Note that various combinations of the disclosed embodiments may be used, and hence reference to an embodiment or one embodiment is not meant to exclude features from that embodiment from use with features from other embodiments. In the claims, the word “comprising” does not exclude other elements or steps, and the indefinite article“a” or “an” does not exclude a plurality. A single processor or other unit may fulfill the functions of several items recited in the claims. The mere fact that certain measures are recited in mutually different dependent claims does not indicate that a combination of these measures cannot be used to advantage. A computer program may be stored/distributed on a suitable medium, such as an optical medium or solid-state medium supplied together with or as part of other hardware, but may also be distributed in other forms. Any reference signs in the claims should be not construed as limiting the scope.

Claims

CLAIMS At least the following is claimed:
1. A computing device, comprising:
a memory comprising instructions; and
one or more processors configured to execute the instructions to:
receive an indication of placement of at least one magnetic resonance spectroscopy voxel on a magnetic resonance image of a biological structure;
determine whether the magnetic resonance spectroscopy voxel placement is proximal to a defined tissue boundary; and
cause a change in a gradient direction, the change in gradient direction adjusting the placement away from the defined tissue boundary to reduce a chemical shift displacement artifact.
2. The computing device of claim 1 , wherein the one or more processors are further configured to execute the instructions to:
receive an indication of a respective size for all dimensions of the at least one magnetic resonance spectroscopy voxel;
determine a shim volume for the at least one magnetic resonance spectroscopy voxel, the shim volume increased in any dimension that is less than a threshold dimension; and
responsive to at least a portion of the shim volume being proximal to the defined tissue boundary, cause a position of the shim volume to be adjusted relative to a default position, the adjustment causing the adjusted position of the shim volume to be further from the defined tissue boundary than the default position.
3. The computing device of claim 2, wherein the one or more processors are further configured to execute the instructions to apply the shim volume according to the adjusted position.
4. The computing device of claim 3, further comprising a display, wherein the one or more processors are further configured to execute the instructions to present the shim volume on the magnetic resonance image according to the adjusted placement.
5. The computing device of claim 1 , wherein the biological structure comprises at least a portion of a brain, wherein the one or more processors are further configured to execute the instructions to determine that the defined tissue boundary comprises one of water in or near ventricles or a lipid in or near a skull.
6. The computing device of claim 1 , wherein the one or more processors are further configured to execute the instructions to:
receive an indication of an additional placement of one or more additional magnetic resonance spectroscopy voxels on a respective location on the imaged biological structure;
determine whether the additional placement of the one or more additional magnetic resonance spectroscopy voxels is proximal to the defined tissue boundary; and
cause a change in a gradient direction, the change in gradient direction adjusting the additional placement away from the defined tissue boundary.
7. The computing device of claim 6, wherein the one or more processors are further configured to execute the instructions to:
receive an indication of a respective size for all dimensions of all of the one or more additional magnetic resonance spectroscopy voxels;
determine a shim volume for each of the one or more additional magnetic resonance spectroscopy voxels, the shim volume increased in any dimension that is less than a threshold dimension; and
responsive to at least a portion of one or more of the shim volumes for the one or more additional magnetic resonance spectroscopy voxels being proximal to the defined tissue boundary, cause a position of each of the proximal shim volumes to be adjusted relative to a default position, the adjustment causing the adjusted position of the proximal shim volumes to be further from the defined tissue boundary than the default position.
8. The computing device of claim 7, wherein the one or more processors are further configured to execute the instructions to apply the respective shim volumes for the one or more additional magnetic resonance spectroscopy voxels according to the adjusted positions.
9. The computing device of claim 6, wherein the one or more processors are further configured to execute the instructions to process the at least one magnetic resonance spectroscopy voxel and the one or more additional magnetic resonance spectroscopy voxels according to the adjusted placement.
10. The computing device of claim 1 , wherein the one or more processors are further configured to execute the instructions to process the at least one magnetic resonance spectroscopy voxel according to the adjusted placement.
11. The computing device of claim 10, further comprising a display, wherein the one or more processors are further configured to execute the instructions to present the magnetic resonance spectroscopy voxel on the display according to the adjusted placement.
12. The computing device of claim 1 , wherein the one or more processors are further configured to execute the instructions to receive the indication of placement of the at least one magnetic resonance spectroscopy voxel on the magnetic resonance image of the biological structure based on user input.
13. The computing device of claim 12, further comprising a user interface configured to receive the user input.
14. The computing device of claim 1 , wherein the one or more processors are further configured to execute the instructions to identify the biological structure via
segmentation of the magnetic resonance image.
15. A non-transitory, computer readable storage medium comprising executable instructions that, when executed by one or more processors, causes the one or more processors to:
receive an indication of placement of at least one magnetic resonance
spectroscopy voxel on a magnetic resonance image of a biological structure;
determine whether the magnetic resonance spectroscopy voxel placement is proximal to a defined tissue boundary; and
cause a change in a gradient direction, the change in gradient direction adjusting the placement away from the defined tissue boundary to reduce a chemical shift displacement artifact.
16. The non-transitory, computer readable storage medium of claim 15, wherein the executable instructions, when executed by the one or more processors, further causes the one or more processors to:
receive an indication of a respective size for all dimensions of the at least one magnetic resonance spectroscopy voxel;
determine a shim volume for the at least one magnetic resonance spectroscopy voxel, the shim volume increased in any dimension that is less than a threshold dimension; and
responsive to at least a portion of the shim volume being proximal to the defined tissue boundary, cause a position of the shim volume to be adjusted relative to a default position, the adjustment causing the adjusted position of the shim volume to be further from the defined tissue boundary than the default position.
17. The non-transitory, computer readable storage medium of claim 16, wherein the executable instructions, when executed by the one or more processors, further causes the one or more processors to apply the shim volume according to the adjusted position.
18. The non-transitory, computer readable storage medium of claim 15, wherein the biological structure comprises at least a portion of a brain, wherein the executable instructions, when executed by the one or more processors, further causes the one or more processors to determine that the defined tissue boundary comprises one of a water voxel in or near ventricles or a lipid voxel in or near a skull based on the segmented brain images.
19. A magnetic resonance spectroscopy voxel planning method, the method comprising:
at one or more processors:
receiving an indication of placement of at least one magnetic resonance spectroscopy voxel on a magnetic resonance image of a biological structure;
determining whether the magnetic resonance spectroscopy voxel placement is proximal to a defined tissue boundary; and
causing a change in a gradient direction, the change in gradient direction adjusting the placement away from the defined tissue boundary to reduce a chemical shift displacement artifact.
20. The method of claim 19, further comprising:
receiving an indication of a respective size for all dimensions of the at least one magnetic resonance spectroscopy voxel;
determining a shim volume for the at least one magnetic resonance
spectroscopy voxel, the shim volume increased in any dimension that is less than a threshold dimension; and responsive to at least a portion of the shim volume being proximal to the defined tissue boundary, cause a position of the shim volume to be adjusted relative to a default position, the adjustment causing the adjusted position of the shim volume to be further from the defined tissue boundary than the default position.
PCT/EP2020/057712 2019-03-29 2020-03-20 Automated voxel positioning for in vivo magnetic resonance spectroscopy WO2020200831A1 (en)

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