Patent Publication Number: US-11041925-B2

Title: Direct measurement of the B0-off-resonance field during magnetic resonance fingerprinting

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
     This application is a U.S. national phase application of International Application No. PCT/EP2017/073974, filed on Sep. 22, 2017, which claims the benefit of EP Application Ser. No. 16/192,638.1 filed on Oct. 6, 2016 and is incorporated herein by reference. 
     FIELD OF THE INVENTION 
     The invention relates to magnetic resonance imaging, in particular to magnetic resonance fingerprinting techniques. 
     BACKGROUND OF THE INVENTION 
     Magnetic Resonance (MR) fingerprinting is a technique where a number of RF pulses often associated with appropriate gradient switching, distributed in time, are applied such that they cause signals from different materials or tissues to have a unique contribution to the measured MR signal. A dictionary of precalculated signal contributions from a large set or a fixed number of substances is compared to the measured MR signals within each single voxel. Furthermore, also the composition within each voxel can further be determined. For example if it is known that a voxel only contains gray matter, white matter, CSF, or fat the contribution from these three materials need only be considered to accurately determine the composition of the voxel. If a larger dictionary with higher resolution is used, MR fingerprinting can be used to determine different tissue parameters of a voxel (such as T1, T2, . . . ) simultaneously and quantitatively. 
     The magnetic resonance fingerprinting technique was introduced in the journal article Ma et al., “Magnetic Resonance Fingerprinting,” Nature, Vol. 495, pp. 187 to 193, doi:10.1038/nature11971. The magnetic fingerprinting technique is also described in United States patent applications US 2013/0271132 A1 and US 2013/0265047 A1. 
     SUMMARY OF THE INVENTION 
     The invention provides for a magnetic resonance imaging system, a method, and a computer program product in the independent claims. Embodiments are given in the dependent claims. 
     In magnetic resonance imaging fingerprinting, various properties of a subject can be included in the dictionary. For example, the concentration of various compounds can be included. Other properties which affect the measured MR signals can also be included. For example the T1 time, T2 time, and other properties. 
     In magnetic resonance imaging, data is typically acquired when the magnetization is in transient state (opposed to conventional steady state imaging). MR fingerprinting relies on pattern recognition algorithms and large parameter data bases. MR fingerprinting is possible through the continuous variation of the acquisition parameters throughout data collection. Ma et al, 2013 describe (pseudo) random variation of parameters. However, also other variation of parameters is possible, e.g. variation by means of an analytical function. To this end MR fingerprinting uses multiple acquisition blocks, identified by a repetition time index. 
     When magnetic resonance imaging is performed, the B0 (or main magnetic field) is according to a simplistic analysis assumed to be uniform. However, non-uniformities in the B0 magnetic field can be caused by a variety of factors. One factor is the magnetic susceptibility of the subject. Various tissues types of tissues have different susceptibilities and thus can distort the B0 magnetic field. This deviation from the orientation of a uniform B0 magnetic field can be expressed in terms of an off-resonant term which modifies the B0 magnetic field to an effective magnetic field. The off-resonant term is referred to herein as the B0-off-resonance field or B0-off-resonance magnetic field. 
     The B0-off-resonance magnetic field may be useful for a variety of things such as precisely calculating chemical shifts within a voxel. Knowledge of the B0-off-resonance magnetic field may also be useful for calculating various electrical properties of the subject. For example the B0-off-resonance magnetic field (also referred to as the off-resonance field or f herein) may be used to calculate the spatially dependent conductivity and/or permittivity of a subject using a technique called MR electric properties tomography. A review of these techniques can be found in the article Voigt et. al. “Quantitative Conductivity and Permittivity Imaging of the Human Brian Using Electric Properties Tomography,” Magnetic Resonance in Medicine 66: 456-466 (2011), pp. 456-466 (referred to as Voigt et. al. herein). Another review of these techniques is contained in the article Katscher et. al. “Recent Progress and Future Challenges in MR Electric Properties Tomography,” Computational and Mathematical Methods in Medicine, Volume 2013, Article ID 546562, 11 pages, http://dx.doi.org/10.1155/2013/546562 (referred to as Katscher et. al. herein). 
     Embodiments of the invention may provide for an improved means of determining the B0-off-resonance magnetic field during MR fingerprinting. Instead of encoding the B0-off-resonance magnetic field in the dictionary, the B0-off-resonance magnetic field is measured directly. The pulse sequence commands are configured to acquire the magnetic resonance data for the MR fingerprinting during multiple pulse repetitions. The gradients of the pulse repetition are configured such that there are at least two occurrences of gradient induced spin rephasing. When the spins rephase a magnetic resonance signal is emitted. This is also commonly referred to as an “echo.” When there are just two magnetic resonance signals then, as described below herein, the inner-product of the signal can be used to directly calculate the B0-off-resonance magnetic field. Once the B0-off-resonance magnetic field is known, it can be used for example Electric Properties Tomography or calculate other quantities, such as precise chemical shifts, to improve the MR fingerprinting. 
     In one aspect the invention provides for a magnetic resonance imaging system for acquiring magnetic resonance data from a subject within an imaging zone. The magnetic resonance imaging system comprises a gradient magnetic field generating system configured for generating a gradient magnetic field within the imaging zone. In some examples, the magnetic field generating system may comprise a gradient coil power supply and one or more magnetic field gradient coils. 
     The magnetic resonance imaging system further comprises a radio-frequency system configured for acquiring the magnetic resonance data. Acquiring the magnetic resonance data may include imaging radio-frequency energy for manipulating the orientation of spins and/or the recording of radio-frequency signals which may also be referred to as magnetic resonance signals herein. The radio-frequency system may comprise an antenna or coil that is connected to a transmitter, receiver or transceiver. The magnetic resonance imaging system further comprises a memory for storing machine-executable instructions and for storing pulse sequence commands. The pulse sequence commands as used herein encompass commands or data which may be converted into commands for controlling the magnetic resonance imaging system to acquire the magnetic resonance data. 
     The pulse sequence commands are configured for controlling the magnetic resonance imaging system to acquire the magnetic resonance data according to a magnetic resonance imaging fingerprinting protocol. The pulse sequence commands are configured for controlling the magnetic resonance imaging system to acquire the magnetic resonance data during multiple pulse repetitions. A portion of the magnetic resonance data is acquired during each of the multiple pulse repetitions. The pulse sequence commands are configured for controlling the magnetic resonance imaging system to cause gradient-induced spin rephasing at least twice during the multiple pulse repetitions using the gradient magnetic field generating system. The gradient-induced spin rephasing may for example be achieved by a magnetic field gradient pulse that is applied and reverses the spatial variation of phase of the transverse magnetization which for example can be caused by a dephasing gradient. The gradient-induced spin rephasing may for example be referred to as a gradient echo. 
     The pulse sequence commands are further configured for controlling the magnetic resonance imaging system to acquire at least two magnetic resonance signals. This is done for each of the multiple pulse repetitions. Each of the at least two magnetic resonance signals is measured during a separate one of the gradient-induced spin rephasings. The magnetic resonance data comprises the at least two magnetic resonance signals acquired during each of the multiple pulse repetitions. 
     The magnetic resonance imaging system further comprises a processor for controlling the magnetic resonance imaging system. Execution of the machine-executable instructions causes the processor to control the magnetic resonance imaging system with the pulse sequence commands to acquire the magnetic resonance data. Execution of the machine-executable instructions further causes the processor to calculate a B0-off-resonance map using the magnetic resonance data. The B0-off-resonance map is descriptive of a B0-off-resonance magnetic field of the magnetic resonance imaging system when the subject is within the imaging zone. The B0-off-resonance map is at least partially calculated using the at least two magnetic resonance signals measured during a single pulse repetition. In magnetic resonance fingerprinting the B0-off-resonance value for a particular voxel may be encoded into the magnetic resonance fingerprinting dictionary. The Nature article by Ma et al. introduces the basic idea of magnetic resonance fingerprinting and terminology which is used to describe this technique such as the dictionary, which is referred to herein as a “precalculated magnetic resonance fingerprinting dictionary,” a “magnetic resonance fingerprinting dictionary,” and a “dictionary.” 
     In the present embodiment, the B0-off-resonance magnetic field is measured directly by comparing the multiple magnetic resonance signals within a single pulse repetition. Within each single pulse repetition a portion of k-space is sampled for each of the at least two MR images with different echo times. The at least two images are then reconstructed after all data have been acquired. Finally, the B0-off-resonance map is calculated voxel-wise based on these at least two images. 
     Execution of the machine-executable instructions further cause the processor to generate at least one magnetic resonance parametric map by comparing the magnetic resonance data within a magnetic resonance fingerprinting dictionary. A magnetic resonance parametric map as described herein encompasses a two or three-dimensional mapping of either a concentration of the subject or an intrinsic property of the subject. For instance various values which may be measured in magnetic resonance such as the T1 time, the T2 time, the M0 map or other values may be represented in the magnetic resonance parametric map. 
     In magnetic resonance fingerprinting, magnetic resonance data is acquired for a variety of flip angles and other magnetic resonance parameters which can be varied within a pulse repetition. The data acquired in a pulse repetition represents a portion of k-space. Multiple pulse repetitions may be combined and then reconstructed into an image. The magnetic resonance fingerprinting is then done by looking at the same voxel within a sequence of these images. The magnetic resonance fingerprinting dictionary comprises an expected value for the value of a voxel for a given set of intrinsic properties such as the T1 value, the T2 value or other properties such as the concentration of water or fat. The value for this voxel within the series of images is then compared to the expected values of the magnetic resonance fingerprinting dictionary. By choosing the dictionary entry which matches the closest or a combination of several different entries the parametric values for a particular voxel may be inferred. 
     This embodiment may be beneficial because it obtains not only magnetic resonance fingerprinting information but it also contains a directly measured B0-off-resonance map. This may have the benefit of avoiding to calculate the B0-off-resonance map using the magnetic resonance fingerprinting dictionary. This may result in more accurate determination of the B0-off-resonance magnetic field. 
     In another embodiment the B0-off-resonance map is calculated at least partially using a complex dot-product of two of the at least two magnetic resonance signals measured during a single pulse repetition. This embodiment may have the means of directly calculating the B0-off-resonance magnetic field. 
     In an alternative, when more than two magnetic resonance measured signals are measured during a single pulse repetition there may be alternate ways of calculating the B0-off-resonance magnetic field. For example the complex dot-product formulation can be calculated for all combinations of two of the magnetic resonance signals. Then various weightings or averages may be used to obtain a single value. This may have the benefit of reducing the amount of noise or variation in the B0-off-resonance map. 
     In another embodiment execution of the machine-executable instructions further cause the processor to calculate at least one magnetic resonance parametric map using component matching. Component matching as used herein is where the contents of two or more variables of the magnetic resonance fingerprinting dictionary contribute to the magnetic resonance signal. For example within a brain, portions of the brain may have signals within a voxel that come from both white and gray matter. In another example a voxel may contain both muscle and fatty tissue. Component matching as used herein is the determination of how much a particular component contributes to the magnetic resonance signal within a voxel. The component matching is performed at least partially by weighting at least a portion of the magnetic resonance fingerprinting dictionary with chemical shift data. For example fat and water tissue may have different effects on the B0 magnetic field. This may result in a different B0-off-resonance map depending upon how much of each tissue type contributes. The chemical shift data is calculated at least partially using the B0-off-resonance map. 
     In some examples, the component matching may represent an iterative process. For example the water and fat composition of a collection of voxels next to each other may have an effect on the B0-off-resonance map. Using an assumption about the fat and water composition of voxels the B0-off-resonance map could be used to calculate an initial chemical shift data. After performing a first loop of the component matching this model could be updated with the calculated content of fat and water within particular voxels and then run again calculated using the new chemical shift data. This could for example be repeated until the answer converges to a solution. 
     In another embodiment execution of the machine-executable instructions further cause the processor to calculate a quantitative susceptibility map using at least partially the B0-off-resonance map. Once the B0-off-resonance map is known a technique known as quantitative susceptibility mapping or QSM may be used to calculate a quantitative susceptibility map. QSM analysis techniques are reviewed in the journal article Wang et. al. “Quantitative Susceptibility Mapping (QSM): Decoding MRI Data for a Tissue Magnetic Biomarker,” Magnetic Resonance in Medicine, 73:82-101 (2015), pp. 82-101 (herein referred to as Wang et. al. 
     In another embodiment the quantitative susceptibility map is at least partially calculated by solving an inverse problem descriptive of a magnetic susceptibility of the subject. The solution of such an inverse problem is for example described in Wang et al. 
     In another embodiment execution of the machine-executable instructions further cause the processor to calculate an RF transmit/receive phase map using the magnetic resonance data. The RF transmit/receive phase map is descriptive of the spatially dependent RF transmit/receive phase. 
     This embodiment may be beneficial because the RF transmit/receive phase map may be useful in calculating various electric properties of the subject in either two or three dimensions. For example the review article (note to self: insert reference by Catcher et al here) describes how the RF transmit/receive phase map may be used for calculating various magnetic resonance electrical properties. 
     In another embodiment execution of the instructions further cause the processor to calculate magnetic resonance electric properties tomographic data using at least partially the RF transmit/receive phase map. Magnetic resonance electric properties tomography data may include such properties as conductivity and permittivity distributions within a subject either two-dimensionally and/or three-dimensionally. The method of calculating such values from the RF transmit/receive phase map is for example detailed in the review article by Katscher et. al. 
     In another embodiment the magnetic resonance fingerprinting dictionary is at least partially a function of the transmit B1 magnetic field magnitude. The at least one magnetic resonance parametric map comprises a transmit B1 magnetic field magnitude map. The magnetic resonance electric properties tomography data is calculated at least partially using the transmit B1 magnetic field magnitude map. This embodiment may be beneficial because a knowledge of the transmit B1 magnetic field may make the magnetic resonance electric properties tomography data calculations more accurate. 
     In another embodiment, execution of the machine-executable instructions further cause the processor to calculate a direct T2-star map at least partially using at least two magnetic resonance signals measured during a single pulse repetition. The direct T2-star map is a T2-star map which is calculated directly using amplitudes of the at least two magnetic resonance signals measured during a single pulse repetition. The term ‘direct’ before the direct T2-star map is intended as a label to differentiate it from T2-star maps or measurements which are made using the magnetic resonance fingerprinting dictionary. T2-star measurements or maps made using the magnetic resonance fingerprinting dictionary are referred to as encoded T2-star maps or measurements. 
     This embodiment may be beneficial because by examining amplitudes of the at least two magnetic resonance signals within a single pulse repetition the T2-star values can be inferred or calculated directly. 
     In another embodiment, the magnetic resonance fingerprinting dictionary is at least partially a function of T2. The at least one magnetic resonance parametric map comprises a T2 map. Execution of the machine-executable instructions further causes the processor to calculate at least partially a T2-prime map from the T2 map and the direct T2-star map. This may have the benefit that the T2-prime map may be useful for such values as predicting the iron content spatially within a subject. The T2′ value can be calculated using the formula: 1/T2′=1/T2−1/T2-star. 
     In another embodiment the magnetic resonance fingerprinting dictionary is at least partially a function of T2-star. The at least one magnetic resonance parametric map comprises an encoded T2-star map. Execution of the machine-executable instructions further cause the processor to calculate an extended T2-star map using the direct T2-star map and the encoded T2-star map. The extended T2-star map is calculated by taking values from within a first predetermined range from the direct T2-star map and from within a second predetermined range from the encoded T2-star map. There may be several benefits in determining the T2-star map in this manner. 
     For instance, when the direct T2-star map is measured the range of T2-star values which can be measured is determined by the temporal distance between the two magnetic resonance signals. When making a direct T2-star map it may be beneficial to choose the time difference such that the decrease in amplitude of the at least two magnetic resonance signals is large in comparison to the noise. In other words, when the direct T2-star map is calculated there is a range for which the T2-star map values are accurate. The encoding of some T2-star values in the magnetic resonance fingerprinting dictionary can therefore extend the range for which the extended T2-star map is accurate. Some of the values are taken from the direct T2-star map and other values are taken from the encoded T2-star map. 
     In another embodiment, the magnetic resonance fingerprinting dictionary is calculated by modeling each of the predetermined substances using an extended phase graph formulation. The extended phase graph formulation is for example described in Weigel, M. (2015), Extended phase graphs: Dephasing, RF pulses, and echoes—pure and simple. J. Magn. Reson. Imaging, 41: 266-295. doi: 10.1002/jmri.24619 and is also described in Scheffler, K. (1999), A pictorial description of steady-states in rapid magnetic resonance imaging. Concepts Magn. Reson., 11: 291-304. doi: 10.1002/(SICI)1099-0534(1999)11:5&lt;291::AID-CMR2&gt;3.0.CO;2-J. 
     In another aspect, the invention provides for a method of operating a magnetic resonance imaging system for acquiring magnetic resonance data from a subject within an imaging zone. The magnetic resonance imaging system comprises a gradient magnetic field generation system configured for generating a gradient magnetic field within the imaging zone. The magnetic resonance imaging system further comprises a radio-frequency system configured for acquiring the magnetic resonance data. The method comprises controlling the magnetic resonance imaging system with pulse sequence commands to acquire the magnetic resonance data. The pulse sequence commands are configured for controlling the magnetic resonance imaging system to acquire the magnetic resonance data according to a magnetic resonance fingerprinting protocol. The pulse sequence commands are configured for controlling the magnetic resonance imaging system to acquire the magnetic resonance data during multiple pulse repetitions. The pulse sequence commands are configured for controlling the magnetic resonance imaging system to cause gradient-induced spin rephasing at least twice during each of the multiple pulse repetitions using the gradient magnetic field generating system. The pulse sequence commands are configured for controlling the magnetic resonance imaging system to acquire at least two magnetic resonance signals during each of the multiple pulse repetitions. Each of the at least two magnetic resonance signals is measured during a separate one of the gradient-induced spin rephasings. The magnetic resonance data comprises the at least two magnetic resonance signals acquired during each of the multiple pulse repetitions. 
     The method further comprises calculating a B0-off-resonance map using the magnetic resonance data. The B0-off-resonance map is descriptive of a B0-off-resonance magnetic field of the magnetic resonance imaging system when the subject is within the imaging zone. The B0-off-resonance map is at least partially calculated using at least two magnetic resonance signals measured during a single pulse repetition. The method further comprises generating at least one magnetic resonance parametric map by comparing the magnetic resonance data with a magnetic resonance fingerprinting dictionary. 
     In another embodiment the B0-off-resonance map is calculated at least partially using a complex-dot-product of two of the at least two magnetic resonance signals measured during a single pulse repetition. 
     In another aspect, the invention provides for a computer program product comprising machine-executable instructions for execution by a processor controlling the magnetic resonance imaging system for acquiring magnetic resonance data from a subject within an imaging zone. The magnetic resonance imaging system comprises a gradient magnetic field generating system configured for generating a gradient magnetic field within the imaging zone. The magnetic resonance imaging system further comprises a radio-frequency system configured for acquiring the magnetic resonance data. 
     Execution of the machine-executable instructions causes the processor to control the magnetic resonance imaging system with pulse sequence commands to acquire the magnetic resonance data. The pulse sequence commands are configured for controlling the magnetic resonance imaging system to acquire the magnetic resonance data according to a magnetic resonance fingerprinting protocol. The pulse sequence commands are configured for controlling the magnetic resonance imaging system to acquire the magnetic resonance data during multiple pulse repetitions. The pulse sequence commands are configured for controlling the magnetic resonance imaging system to cause gradient-induced spin rephasing at least twice during each of the multiple pulse repetitions using the gradient magnetic field generating system. The pulse sequence commands are configured for controlling the magnetic resonance imaging system to acquire at least two magnetic resonance signals during each of the multiple pulse repetitions. Each of the at least two magnetic resonance signals is measured during a separate one of the gradient-induced spin rephasing. The magnetic resonance data comprises the at least two magnetic resonance signals acquired during each of the multiple pulse repetitions. 
     Execution of the machine-executable instructions further causes the processor to calculate a B0-off-resonance map using the magnetic resonance data. The B0-off-resonance map is descriptive of a B0-off-resonance magnetic field of the magnetic resonance imaging system when the subject is within the imaging zone. The B0-off-resonance map is at least partially calculated using at least two magnetic resonance signals measured during a single pulse repetition. Execution of the machine-executable instructions further cause the processor to generate at least one magnetic resonance parametric map by comparing the magnetic resonance data with a magnetic resonance fingerprinting dictionary. 
     In another embodiment the B0-off-resonance map is calculated at least partially using a complex-dot-product of two of the at least two magnetic resonance signals measured during a single pulse repetition. 
     It is understood that one or more of the aforementioned embodiments of the invention may be combined as long as the combined embodiments are not mutually exclusive. 
     As will be appreciated by one skilled in the art, aspects of the present invention may be embodied as an apparatus, method or computer program product. Accordingly, aspects of the present invention may take the form of an entirely hardware embodiment, an entirely software embodiment (including firmware, resident software, micro-code, etc.) or an embodiment combining software and hardware aspects that may all generally be referred to herein as a “circuit,” “module” or “system.” Furthermore, aspects of the present invention may take the form of a computer program product embodied in one or more computer readable medium(s) having computer executable code embodied thereon. 
     Any combination of one or more computer readable medium(s) may be utilized. The computer readable medium may be a computer readable signal medium or a computer readable storage medium. A ‘computer-readable storage medium’ as used herein encompasses any tangible storage medium which may store instructions which are executable by a processor of a computing device. The computer-readable storage medium may be referred to as a computer-readable non-transitory storage medium. The computer-readable storage medium may also be referred to as a tangible computer readable medium. In some embodiments, a computer-readable storage medium may also be able to store data which is able to be accessed by the processor of the computing device. Examples of computer-readable storage media include, but are not limited to: a floppy disk, a magnetic hard disk drive, a solid state hard disk, flash memory, a USB thumb drive, Random Access Memory (RAM), Read Only Memory (ROM), an optical disk, a magneto-optical disk, and the register file of the processor. Examples of optical disks include Compact Disks (CD) and Digital Versatile Disks (DVD), for example CD-ROM, CD-RW, CD-R, DVD-ROM, DVD-RW, or DVD-R disks. The term computer readable-storage medium also refers to various types of recording media capable of being accessed by the computer device via a network or communication link. For example a data may be retrieved over a modem, over the internet, or over a local area network. Computer executable code embodied on a computer readable medium may be transmitted using any appropriate medium, including but not limited to wireless, wire line, optical fiber cable, RF, etc., or any suitable combination of the foregoing. 
     A computer readable signal medium may include a propagated data signal with computer executable code embodied therein, for example, in baseband or as part of a carrier wave. Such a propagated signal may take any of a variety of forms, including, but not limited to, electro-magnetic, optical, or any suitable combination thereof. A computer readable signal medium may be any computer readable medium that is not a computer readable storage medium and that can communicate, propagate, or transport a program for use by or in connection with an instruction execution system, apparatus, or device. 
     ‘Computer memory’ or ‘memory’ is an example of a computer-readable storage medium. Computer memory is any memory which is directly accessible to a processor. ‘Computer storage’ or ‘storage’ is a further example of a computer-readable storage medium. Computer storage may be any volatile or non-volatile computer-readable storage medium. 
     A ‘processor’ as used herein encompasses an electronic component which is able to execute a program or machine executable instruction or computer executable code. References to the computing device comprising “a processor” should be interpreted as possibly containing more than one processor or processing core. The processor may for instance be a multi-core processor. A processor may also refer to a collection of processors within a single computer system or distributed amongst multiple computer systems. The term computing device should also be interpreted to possibly refer to a collection or network of computing devices each comprising a processor or processors. The computer executable code may be executed by multiple processors that may be within the same computing device or which may even be distributed across multiple computing devices. 
     Computer executable code may comprise machine executable instructions or a program which causes a processor to perform an aspect of the present invention. Computer executable code for carrying out operations for aspects of the present invention may be written in any combination of one or more programming languages, including an object oriented programming language such as Java, Smalltalk, C++ or the like and conventional procedural programming languages, such as the C programming language or similar programming languages and compiled into machine executable instructions. In some instances the computer executable code may be in the form of a high level language or in a pre-compiled form and be used in conjunction with an interpreter which generates the machine executable instructions on the fly. 
     The computer executable code may execute entirely on the user&#39;s computer, partly on the user&#39;s computer, as a stand-alone software package, partly on the user&#39;s computer and partly on a remote computer or entirely on the remote computer or server. In the latter scenario, the remote computer may be connected to the user&#39;s computer through any type of network, including a local area network (LAN) or a wide area network (WAN), or the connection may be made to an external computer (for example, through the Internet using an Internet Service Provider). 
     Aspects of the present invention are described with reference to flowchart illustrations and/or block diagrams of methods, apparatus (systems) and computer program products according to embodiments of the invention. It is understood that each block or a portion of the blocks of the flowchart, illustrations, and/or block diagrams, can be implemented by computer program instructions in form of computer executable code when applicable. It is further understood that, when not mutually exclusive, combinations of blocks in different flowcharts, illustrations, and/or block diagrams may be combined. These computer program instructions may be provided to a processor of a general purpose computer, special purpose computer, or other programmable data processing apparatus to produce a machine, such that the instructions, which execute via the processor of the computer or other programmable data processing apparatus, create means for implementing the functions/acts specified in the flowchart and/or block diagram block or blocks. 
     These computer program instructions may also be stored in a computer readable medium that can direct a computer, other programmable data processing apparatus, or other devices to function in a particular manner, such that the instructions stored in the computer readable medium produce an article of manufacture including instructions which implement the function/act specified in the flowchart and/or block diagram block or blocks. 
     The computer program instructions may also be loaded onto a computer, other programmable data processing apparatus, or other devices to cause a series of operational steps to be performed on the computer, other programmable apparatus or other devices to produce a computer implemented process such that the instructions which execute on the computer or other programmable apparatus provide processes for implementing the functions/acts specified in the flowchart and/or block diagram block or blocks. 
     A ‘user interface’ as used herein is an interface which allows a user or operator to interact with a computer or computer system. A ‘user interface’ may also be referred to as a ‘human interface device.’ A user interface may provide information or data to the operator and/or receive information or data from the operator. A user interface may enable input from an operator to be received by the computer and may provide output to the user from the computer. In other words, the user interface may allow an operator to control or manipulate a computer and the interface may allow the computer indicate the effects of the operator&#39;s control or manipulation. The display of data or information on a display or a graphical user interface is an example of providing information to an operator. The receiving of data through a keyboard, mouse, trackball, touchpad, pointing stick, graphics tablet, joystick, gamepad, webcam, headset, pedals, wired glove, remote control, and accelerometer are all examples of user interface components which enable the receiving of information or data from an operator. 
     A ‘hardware interface’ as used herein encompasses an interface which enables the processor of a computer system to interact with and/or control an external computing device and/or apparatus. A hardware interface may allow a processor to send control signals or instructions to an external computing device and/or apparatus. A hardware interface may also enable a processor to exchange data with an external computing device and/or apparatus. Examples of a hardware interface include, but are not limited to: a universal serial bus, IEEE 1394 port, parallel port, IEEE 1284 port, serial port, RS-232 port, IEEE-488 port, bluetooth connection, wireless local area network connection, TCP/IP connection, ethernet connection, control voltage interface, MIDI interface, analog input interface, and digital input interface. 
     A ‘display’ or ‘display device’ as used herein encompasses an output device or a user interface adapted for displaying images or data. A display may output visual, audio, and or tactile data. Examples of a display include, but are not limited to: a computer monitor, a television screen, a touch screen, tactile electronic display, Braille screen, Cathode ray tube (CRT), Storage tube, Bi-stable display, Electronic paper, Vector display, Flat panel display, Vacuum fluorescent display (VF), Light-emitting diode (LED) display, Electroluminescent display (ELD), Plasma display panel (PDP), Liquid crystal display (LCD), Organic light-emitting diode display (OLED), a projector, and Head-mounted display. 
     Magnetic Resonance (MR) data is defined herein as being the recorded measurements of radio frequency signals emitted by atomic spins using the antenna of a magnetic resonance apparatus during a magnetic resonance imaging scan. Magnetic resonance data is an example of medical imaging data. A Magnetic Resonance (MR) image is defined herein as being the reconstructed two or three dimensional visualization of anatomic data contained within the magnetic resonance imaging data. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       In the following preferred embodiments of the invention will be described, by way of example only, and with reference to the drawings in which: 
         FIG. 1  illustrates and example of a magnetic resonance imaging system; 
         FIG. 2  shows a flow chart with an exemplary method of operating the magnetic resonance imaging system of  FIG. 1 ; 
         FIG. 3  shows several plots which are used to illustrate some details of pulse sequence commands suitable for performing the method illustrated in  FIG. 2 ; and 
         FIG. 4  shows a flow chart which illustrates a method of analyzing magnetic resonance data. 
     
    
    
     DETAILED DESCRIPTION OF THE EMBODIMENTS 
     Like numbered elements in these Figs are either equivalent elements or perform the same function. Elements which have been discussed previously will not necessarily be discussed in later Figs if the function is equivalent. 
       FIG. 1  shows an example of a magnetic resonance imaging system  100  with a magnet  104 . The magnet  104  is a superconducting cylindrical type magnet with a bore  106  through it. The use of different types of magnets is also possible; for instance it is also possible to use both a split cylindrical magnet and a so called open magnet. A split cylindrical magnet is similar to a standard cylindrical magnet, except that the cryostat has been split into two sections to allow access to the iso-plane of the magnet, such magnets may for instance be used in conjunction with charged particle beam therapy. An open magnet has two magnet sections, one above the other with a space in-between that is large enough to receive a subject: the arrangement of the two sections area similar to that of a Helmholtz coil. Open magnets are popular, because the subject is less confined. Inside the cryostat of the cylindrical magnet there is a collection of superconducting coils. Within the bore  106  of the cylindrical magnet  104  there is an imaging zone  108  where the magnetic field is strong and uniform enough to perform magnetic resonance imaging. A region of interest  109  is shown within the imaging zone  108 . A subject  118  is shown as being supported by a subject support  120  such that at least a portion of the subject  118  is within the imaging zone  108  and the region of interest  109 . 
     Within the bore  106  of the magnet there is also a set of magnetic field gradient coils  110  which is used for acquisition of magnetic resonance data to spatially encode magnetic spins within the imaging zone  108  of the magnet  104 . The magnetic field gradient coils  110  connected to a magnetic field gradient coil power supply  112 . The magnetic field gradient coils  110  are intended to be representative. Typically magnetic field gradient coils  110  contain three separate sets of coils for spatially encoding in three orthogonal spatial directions. A magnetic field gradient power supply supplies current to the magnetic field gradient coils. The current supplied to the magnetic field gradient coils  110  is controlled as a function of time and may be ramped or pulsed. 
     Adjacent to the imaging zone  108  is a radio-frequency coil  114  for manipulating the orientations of magnetic spins within the imaging zone  108  and for receiving radio transmissions from spins also within the imaging zone  108 . The radio frequency antenna may contain multiple coil elements. The radio frequency antenna may also be referred to as a channel or antenna. The radio-frequency coil  114  is connected to a radio frequency transceiver  116 . The radio-frequency coil  114  and radio frequency transceiver  116  may be replaced by separate transmit and receive coils and a separate transmitter and receiver. It is understood that the radio-frequency coil  114  and the radio frequency transceiver  116  are representative. The radio-frequency coil  114  is intended to also represent a dedicated transmit antenna and a dedicated receive antenna. Likewise the transceiver  116  may also represent a separate transmitter and receivers. The radio-frequency coil  114  may also have multiple receive/transmit elements and the radio frequency transceiver  116  may have multiple receive/transmit channels. For example if a parallel imaging technique such as SENSE is performed, the radio-frequency could  114  will have multiple coil elements. 
     The transceiver  116  and the gradient controller  112  are shown as being connected to a hardware interface  128  of a computer system  126 . The computer system further comprises a processor  130  that is in communication with the hardware system  128 , a memory  134 , and a user interface  132 . The memory  134  may be any combination of memory which is accessible to the processor  130 . This may include such things as main memory, cached memory, and also non-volatile memory such as flash RAM, hard drives, or other storage devices. In some examples the memory  130  may be considered to be a non-transitory computer-readable medium. 
     The computer memory  134  is shown as containing machine-executable instructions  140 . The machine-executable instructions contain commands or instructions which enable the processor  130  to control the operation and function of the magnetic resonance imaging system  100 . The computer memory  134  is shown as further containing pulse sequence commands  142 . The pulse sequence commands  142  are either instructions or data which may be converted into instructions which enable the processor  130  to control the magnetic resonance imaging system  100  to acquire magnetic resonance data. The magnetic resonance data may for instance be used to cause the magnetic resonance imaging system to perform multiple pulse repetitions which cause magnetic resonance signals  144  to be acquired. 
     Magnetic resonance signals  144  are shown as being stored in the computer memory  134 . The magnetic resonance signals  144  for a particular pulse repetition may be collated into the magnetic resonance data  146 . The magnetic resonance data  146  may be used to generate a series of intermediate images  148 . The intermediate images are acquired and reconstructed in a series which is used to form the magnetic resonance fingerprint for various voxels. The computer memory  134  is shown as containing a magnetic resonance parametric map  150  and a magnetic resonance fingerprinting dictionary  152 . 
     The intermediate images  148  are compared for a particular voxel to the magnetic resonance fingerprinting dictionary  152 . This is compared to entries within a magnetic resonance fingerprinting dictionary and a map of various intrinsic properties such as T1, T2 or various concentrations of substances can be inferred. The results of the analysis may be constructed into a two or three-dimensional dataset which is the magnetic resonance parametric map  150 . The computer memory  134  is shown as further containing an optional magnetic resonance fingerprinting model  154  which may be used to generate a magnetic resonance fingerprinting dictionary  152  from pulse sequence commands  142 . The computer memory  134  also optionally is shown as containing image processing command library  156  which contains commands which enable the processor  130  to perform various image processing operations such as extracting a voxel from the series of intermediate images  148 . 
     The computer memory  134  is shown as containing additionally a B0-off-resonance map  158  that was calculated from groups of magnetic resonance signals  144 . The computer memory  134  is further shown as containing chemical shift data  160  that was calculated from the B0-off-resonance map  158 . The computer memory  134  is further shown as containing an RF transmit/receive phase map  162  that was also calculated from groups of the magnetic resonance signals  144 . 
       FIG. 2  shows a flowchart which illustrates a method of operating the magnetic resonance imaging system  100  of  FIG. 1 . First in step  200  the magnetic resonance imaging system is controlled with the pulse sequence commands  142 . These cause the magnetic resonance imaging system to acquire the magnetic resonance signals  144  and data  146 . The pulse sequence commands  142  are configured for controlling the magnetic resonance imaging system  100  to acquire the magnetic resonance data  146  according to a magnetic resonance fingerprinting protocol. The pulse sequence commands are configured for controlling the magnetic resonance imaging system  100  to acquire the magnetic resonance data  146  during multiple pulse repetitions. 
     The pulse sequence commands are configured for controlling the magnetic resonance imaging system to cause gradient-induced spin rephasing at least twice during each of the multiple pulse repetitions using the gradient magnetic field generation system  110 ,  112 . The pulse sequence commands are configured for controlling the magnetic resonance imaging system  100  to acquire at least two magnetic resonance signals  144  during each of the multiple pulse repetitions. Each of the at least two magnetic resonance signals is measured during a separate one of the gradient-induced spin rephasings. The magnetic resonance data comprises the at least two magnetic resonance signals  144  acquired during each of the multiple pulse repetitions. 
     Next in step  202  the B0-off-resonance map  158  is calculated using the magnetic resonance data  146 . The B0-off-resonance map  158  is descriptive of a B0-off-resonance magnetic field of the magnetic resonance imaging system  100  when the subject  118  is within the imaging zone  108 . The B0-off-resonance map  158  is at least partially calculated using at least two magnetic resonance signals  144  measured during a single pulse repetition. Finally in step  204  at least one magnetic resonance parametric map  150  is generated by comparing the magnetic resonance data  146 , which in this case has been transformed into the form of the intermediate images, with the magnetic resonance fingerprinting dictionary  152 . 
     Magnetic Resonance Fingerprinting (MRF) is a new acquisition and reconstruction technique in the field of Magnetic Resonance Imaging (MRI). Instead of acquiring data for a given set of sequence parameters, which results in images with predefined contrast, MRF collects data while varying sequence parameters. The resulting so-called fingerprint is matched with a dictionary of signal evolutions computed in advance assuming characteristic tissue parameters, which results in the simultaneous estimation of said tissue characteristics. MRF has so far been implemented using a balanced gradient-echo (b-SSFP, True-FISP, . . . ) sequence or a gradient-spoiled gradient-echo (N-FFE, FISP, . . . ) sequence. 
     Using b-SSFP, the B0-off-resonance field in the time-evolution of the spin system is directly modelled in the dictionary computation to account for the well-known banding-artifacts. The second approach, based on gradient-spoiling, overcomes the explicit dependence of the signal magnitude in the dictionary entries on the B0-off-resonance. This greatly reduces the number of dictionary entries and simplifies the matching process. At the same time, however, the information about the B0-off-resonance distribution is no longer directly available, since the signal phase not only contains the B0-off-resonance but also the RF transmit/receive phase. 
     Examples may allow for the acquisition of data at a range of different echo-times during the fingerprinting sequence. This allows the determination and separation of the B0-off-resonance field and the transmit/receive phase without time-consuming and calculation-intense dictionary matching. In addition, the variation of the signal magnitude between data acquired for different echo-times can be exploited to determine the transverse relaxation time T2* (T2-star). Thus, in combination with T2 from dictionary-matching, the reversible transverse relaxation time 1/T2′=1/T2−1/T2* can be estimated as well. 
     A feature of some examples is the direct use of the measured signal from MRF, acquired with variable echo-times, to determine the B0-off-resonance field, the transmit/receive phase and/or T2*. This is in contrast to the usual procedure of dictionary matching to determine the physical parameters of the studied system. 
     In addition, examples may utilize the resulting information to determine the magnetic susceptibility via quantitative susceptibility mapping (QSM), which uses the B0-off-resonance field to determine the electric conductivity via electric properties tomography (EPT), which uses the transmit/receive phase ϕ TXRX  and possibly determine the transverse relaxation time T2-star from the variation of the signal magnitude as a function of echo-time. Finally, both magnitude and phase of the acquired signals at different echo times and flip angles may be employed to improve the accuracy of MRF-based component matching by including prior knowledge about the chemical shift between different components. 
       FIG. 3  illustrates some parameters used in the pulse sequence commands  142 . Not all parameters in the pulse sequence commands  142  are illustrated. Of particular note the gradients are not noted and also the temporal position of the RF pulses is not illustrated. There are four plots. The x-axis  302  represents an individual pulse repetition. The plot with the y-axis labeled  304  illustrates the magnitude of the flip angle  304 . The plot with the y-axis labeled  306  shows the repetition time of various pulse repetitions  302 . In this case the repetition time or TR is kept constant. The plot with the axis labeled  308  shows the time of the first echo. The plot with the y-axis labeled  310  shows the time when the second echo is acquired. The data acquired at the echo times  308  and  310  are the magnetic resonance signals. In this particular example only two are acquired. The pulse sequence will additionally have magnetic field gradients to perform spatial encoding and also to refocus it such that there are gradient echoes at TE1 and TE2. The flip angle  304  is shown as varying nearly smoothly between the different pulse repetitions  302 . This may result in better results as there is less variation between adjacent pulse repetitions. This may lead to a more stable answer. However, the use of a pseudo-random or pseudo-random variant flip angle  304  is also possible. 
     The Magnetic Resonance Fingerprinting (MRF) Acquisition in some examples may proceed by acquiring data after each RF-excitation for a predetermined, arbitrary sequence of flip-angles, repetition times and RF-transmit phase angles, see  FIG. 3 . Instead of varying only the flip-angle, the (global) RF-transmit phase and the repetition time, the readout module may employ different gradient waveforms to sample the center of k-space at variable times after the RF-pulse. 
     The echo-time may be determined by the time of gradient-induced spin rephasing, and can be varied by choosing any variant readout-module, e.g., spiral, radial or Cartesian. For example, keeping the repetition-time constant, the echo-time could be chosen to alternate between close to zero and almost TR, by alternating between an outward spiral readout and an inward spiral readout. Alternatively, keeping the readout waveform constant, the echo-time could be varied by simply delaying the start of the readout gradient waveform for a given amount of time. Alternatively, two identical readouts for a single excitation could be used. 
     Determination of f, ϕ TXRX , T* 2    
     The modulation of the complex MR-signal due to varying T E  can be modelled as 
     
       
         
           
             
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     Here, M 0  contains the effect of all other sequence and tissue parameters for the given fingerprint. The off-resonance field f induces the same phase-shift for any shot during the fingerprint. It can therefore be measured directly from the two complex fingerprinting signals, acquired at different echo-times, for example, by computing the inner-product of the signals:
 
2π( TE   2   −TE   1 ) f =angle(Σ i     S   ι ( TE   1 )   S   i ( TE   2 )).
 
     Here, it is assumed for the sake of argument that for each combination of sequence parameters in the fingerprinting sequence two signals are acquired that only differ by their T E . 
     Alternatively, the produced images for each shot of the fingerprinting sequence could be used directly to determine f (the B0-off-resonance magnetic field) and ϕ TXRX  (RF Transmit/Receive Phase) from the signal phase ϕ(T E )=angle(S(T E )) from linear regression using the model ϕ(T E )=ϕ TXRX +2πfT E , or any other method described in the literature.
         Similarly, T2* (T2-star) can be determined for example using:       

     
       
         
           
             
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     Again, other and/or more involved methods using nonlinear fitting and/or multiple echo-times can be used when available. 
     For example, Dictionary-matching as usual in Magnetic Resonance Fingerprinting may be used to determine quantities such as: T1, T2, M0, or etc. 
     The additional B0-off-resonance information can be employed to improve component matching using MRF. To this end, the chemical shift σ between different components is included in the data analysis. The measured phase for a particular echo time is then given by:
 
ϕ( T   E ,α)=ϕ TXRX   +γΔB   0   χ   T   E +ψ( T   E ,α,{right arrow over ( T   1 )},{right arrow over ( T   2 )},{right arrow over ( T*   2 )},{right arrow over (σ)}),(*)
 
     where α is the flip angle, ΔB_0{circumflex over ( )}χ is the B0-off-resonance due to susceptibility, and {right arrow over (T 1 )}, {right arrow over (T 2 )}, {right arrow over (T* 2 )}, and {right arrow over (σ)} are the tissue properties for the different components. The phase ψ is given by: 
     
       
         
           
             
               
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     where w i  are the fractions of the different components in the voxel. In contrast to the first two terms in eq. (*), the phase ψ exhibits a dependence on the flip angle, which can be used to disentangle the two contributions. Since the chemical shifts between different components are known, they can be included as prior information in the matching procedure. The fractions w i  are then selected to yield the best agreement between measured and simulated signal amplitudes and phases. 
     Quantitative Susceptibility Mapping (QSM) can be applied to the B0-off-resonance field ΔB 0   χ  to determine the local tissue magnetic susceptibility (see for example Wang et al.). Briefly, the B0-off-resonance field map is related to the susceptibility distribution χ, by convolution with the dipole-operator D according to 
               Δ   ⁢           ⁢     B   0   χ       =         γ   ⁢           ⁢     B   0         2   ⁢   π       ⁢     D   ⊗     χ   .               
This defines an ill-posed, ill-conditioned inverse problem, which can be solved employing various regularization techniques described in the literature (see for example Wang et at.).
 
     The electric conductivity σ can be determined using the transmit/receive phase by applying EPT (see for example Voigt et. al.). Briefly, and in its most simple form, the electric conductivity of the tissue at the Larmor frequency can be shown to be determined by the curvature of the transmit-receive phase ϕ TXRX  (‘phase-based EPT’) according to 
             σ   =       1     2   ⁢     ωμ   0         ⁢         ∇   2     ⁢     ϕ   TXRX       .             
Here, ω is the Larmor frequency, μ 0  is the magnetic permeability and ∇ 2  is the Laplace operator.
 
     The combination T2* and T2, determined by dictionary-matching results in an estimate of the reversible component of the transverse relaxation time, defined as 1/T2′:=1/T2−1/T2*. This parameter has been suggested as a measure of iron content (Haacke 2005). 
       FIG. 4  shows a flowchart which illustrates part of the data acquisition and data analysis. The block labeled  1  and also  200  represents the acquisition of the magnetic resonance fingerprinting data that yields four-dimensional data. The data from step  200  may be processed in several different ways. The method may then proceed to step  202  where the B0-off-resonance map is calculated. During this step additionally the RF transmit/receive phase map and the direct T2-star map may also be calculated. The data from step  200  may also be used to perform a dictionary mapping  204 . In the dictionary mapping at least one magnetic resonance parametric map may be calculated. The values determined in step  202  may be used in several different ways. For example the B0-off-resonance map may be used in combination with the dictionary mapping to improve component matching and determine such things as the myelin fraction or the fat fraction in a voxel. The data from step  202  may also be used for performing a further analysis to calculate a quantitative susceptibility map  400  or to perform magnetic resonance electric properties tomography  402 . Detectability 
     The production of the additional quantitative maps from the MRF data could be directly visible to the user in a clinical setting. Improved off-resonance-maps, etc. without the need for additional and time-consuming dictionary-matching may accelerate the presentation of results. 
     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. 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 measured cannot be used to advantage. A computer program may be stored/distributed on a suitable medium, such as an optical storage medium or a solid-state medium supplied together with or as part of other hardware, but may also be distributed in other forms, such as via the Internet or other wired or wireless telecommunication systems. Any reference signs in the claims should not be construed as limiting the scope. 
     LIST OF REFERENCE NUMERALS 
     
         
         
           
               100  magnetic resonance imaging system 
               104  magnet 
               106  bore of magnet 
               108  imaging zone 
               109  region of interest 
               110  magnetic field gradient coils 
               112  magnetic field gradient coil power supply 
               114  radio-frequency coil 
               116  transceiver 
               118  subject 
               120  subject support 
               126  computer system 
               128  hardware interface 
               130  processor 
               132  user interface 
               134  computer memory 
               140  machine executable instructions 
               142  pulse sequence commands 
               144  magnetic resonance signals 
               146  magnetic resonance data 
               148  intermediate images 
               150  magnetic resonance parametric map 
               152  magnetic resonance fingerprinting dictionary 
               154  magnetic resonance fingerprinting model 
               156  image processing command library 
               158  B0-off-resonance map 
               160  chemical shift data 
               162  RF transmit/receive phase map 
               200  control the magnetic resonance imaging system with the pulse sequence commands to acquire the magnetic resonance data 
               202  calculate a B0-off-resonance map using the magnetic resonance data, wherein the B0-off-resonance map is descriptive of a B0-off-resonance magnetic field of the magnetic resonance imaging system when the subject is within the imaging zone 
               204  generate at least one magnetic resonance parametric map by comparing the magnetic resonance data with a magnetic resonance fingerprinting dictionary 
               300  pulse sequence commands 
               302  pulse repetitions 
               304  flip angle [FA] 
               306  pulse repetition time [TR] 
               308  echo time 1 [ET1] 
               310  echo time 2 [ET2] 
               400  QSM analysis 
               402  EPT analysis 
               406  component analysis during MR fingerprinting