Abstract:
In a method and apparatus for acquiring magnetic resonance data, a resting state functional magnetic resonance imaging sequence is executed in alternation with a morphological data acquisition sequence. The alternating sequences are executed with no time interruptions therebetween, with at least one repetition of the alternating sequences. The resting state functional magnetic resonance imaging sequence can be a BOLD-EPI sequence, and the morphological imaging sequence can be an MPRAGE sequence.

Description:
BACKGROUND OF THE INVENTION 
     Field of the Invention 
     The present invention is concerned with a method and an apparatus for resting state functional magnetic resonance imaging (rsfMRI). 
     Description of the Prior Art 
     Magnetic resonance imaging is an imaging modality that makes use of the fact that different types of nuclei are resonant at respectively different frequencies in a magnetic field of a given field strength. Each type of nuclei exhibits a property known as the gyromagnetic ratio, which causes that nucleus to resonate at a specific frequency in the presence of a magnetic field of a specific field strength. The nuclei are initially aligned by the strong magnetic field, and, by the application of radio-frequency (RF) energy thereto, are deflected by an angle (called the “flip angle”) from the aligned state. As the deflected nuclei return to the aligned state, they emit RF signals (magnetic resonance signals) which are detected and processed in order to generate a magnetic resonance image. 
     A special category of magnetic resonance imaging is functional magnetic resonance imaging (fMRI). As explained in U.S. Pat. No. 7,349,728 (the teachings of which are incorporated herein by reference), functional magnetic resonance tomography makes use of the fact that the oxygen content of blood influences its magnetic properties. The magnetic resonance characteristics, and thus the magnetic resonance signal generated by blood, change with the content of oxygenated or de-oxygenated hemoglobin. Therefore, blood behaves in functional magnetic resonance tomography in the manner of a contrast medium. With a high proportion of de-oxygenated hemoglobin, as a result of its paramagnetic characteristics in the environment of the blood vessels, a local magnetic field gradient is induced which, with a suitable choice of a magnetic resonance tomography sequence, a localized signal reduction will occur. If the proportion of oxygenated hemoglobin in the blood increases, an effect known as the susceptibility effect decreases, which leads to an increase in the measured signal. This relationship is referred to as the BOLD (blood oxygen level dependent) contrast, or BOLD effect. With increasing field strength, this effect is increased. Magnetic resonance devices (scanners) that generate a basic magnetic field strength of 1.5 Tesla and higher are used for fMRI. 
     The magnetic resonance sequence that is typically used in fMRI is an echo planar imaging sequence, so that fMRT is a type of echo planar imaging. 
     The local changes of the oxygen content in the blood can be caused, for example, by intentionally subjecting the patient to one or more sensory inputs (such as light, sound or touch) at known times, and the fMRI image will enable a physician to identify the location in the brain at which increased brain activity occurs as a result of the stimulus. 
     Resting state fMRI (rsfMRI) is a form of fMRI wherein BOLD signals are acquired from a subject with no external stimuli being applied. The BOLD signals are then statistically analyzed to determine degrees of connectivity between various regions of the brain. In general, the greater that a low frequency (such as below approximately 0.1 Hz) modulation of the BOLD signals between two brain regions is correlated over time, the higher the respective connectivity between those two regions. 
     This technique is robust with individual patients, and allows the same scan to be used to survey multiple brain systems, in contrast to conventional task-based BOLD examinations. Investigations have shown that rsfMRI can be used to identify brain systems that are associated with motor function, and associated with cognition, including language and memory. Major clinical applications include early stage diagnosis of Alzheimer&#39;s disease, grading depression severity, pre-surgical planning, and transcranial magnetic stimulation (TMS) targeting. In clinical practice, rsfMRI sequences are commonly used in conjunction with structural or anatomical (morphological) sequences, such as a 3D MPRAGE (Magnetization Prepared Rapid Gradient Echo) sequence. Conventionally, data are acquired from the examination subject using an rsfMRI sequence, and then a separate examination takes place wherein data are acquired from the subject using a morphological sequence, such as MPRAGE. For example, in early stage diagnosis of Alzheimer&#39;s disease, rsfMRI data are combined, after such separated acquisitions, with morphological MRI data, from which brain atrophy can be identified from the structural sequence. In pre-surgical planning for temporal lobe epilepsy and tumor reception, and TMS targeting for depression, the functional measurements acquired from the rsfMRI data are directly referenced to the anatomical structural data acquired from the morphological sequence from the same patient. 
     In view of the need to acquire data both in a structural sequence and in an rsfMRI sequence, the overall measurement (data acquisition) time can be prolonged so as to have a duration of 15 to 30 minutes. This can present a significant problem in the case of elderly patients, demented patients, or severely depressed patients. It is thus of major interest to significantly reduce the total measurement time in these types of examinations. 
     SUMMARY OF THE INVENTION 
     In accordance with the invention, functional rsfMRI sequences are interleaved with morphological MR sequences, allowing acquisition (measurement) of both functional data and morphological data in rapid succession, with no time interruptions between successive sequences, so as to reduce the total scan time by approximately half the time required for conventional, time-separated functional data acquisition and morphological data acquisition. 
     The present invention encompasses a method for acquiring functional and morphological magnetic resonance data wherein multiple rsfMRI sequences are interleaved with multiple morphological data acquisition sequences. As used herein, “interleaved” means that the respective different types of sequences alternate in time with each other with no time gap or interruption between any two successive sequences. 
     The invention also encompasses a magnetic resonance imaging apparatus that is operable to implement such a method as well as a non-transitory, computer-readable data storage medium encoded with programming instructions that, when the storage medium is loaded into a computerized control unit of a magnetic resonance imaging apparatus, caused the apparatus to execute the method in accordance with the invention. 
     The rsfMRI sequence is preferably an EPI-BOLD sequence, and the morphological imaging sequence is preferably an MPRAGE sequence. 
     The invention is based on the insight that the functional data are band-limited, allowing for interleaving with time constants in the range of sub-seconds. 
     As is known in magnetic resonance imaging, the raw data acquired from the examination subject are entered into a memory in an organized manner, this memory format being known as k-space. K-space can be two-dimensional or three-dimensional, and includes multiple points at which respective data entries are made. The filling of k-space (i.e., entering data values into k-space at the respective points thereof) is known as scanning or sampling k-space, and the sequence and path along which respective data points in k-space are filled is known as a k-space trajectory. In accordance with the present invention, a linear (line-by-line) trajectory can be used, but optimized k-space trajectories such as spirals and radial paths can also be used, in order to reduce acoustic noise. 
     As noted above, current research indicates that resting state functional information is band-limited to a window around 0.1 Hz. Therefore, according to the Nyquist theorem, a morphological sequence component can be interleaved with resting state functional information, without loss of information, up to a certain limit of the switching time, i.e., the respective durations of the interleaved sequences. If it is assumed, for example, that a conventional rsfMRI EPI sequence is used, that repeatedly scans 2D or 3D k-space in a non-segmented or segmented fashion, after k-space readouts of rsfMRI information for a duration of dt 1  seconds, a morphological readout sequence such as MPRAGE can be implemented for a duration of dt 2  seconds, and so on. In a preferred embodiment, dt 1 =dt 2 =0.1 s, up to 5 s-Δ, with Δ being the aforementioned time limit that accounts for the bandwidth. For example, Δ=1 s. This allows recovery of the most important phase information around the center frequency of 0.1 Hz. 
     Other research has noted, however, that resting state modulations may also occur around higher carrier frequencies, such as around 0.3 Hz, which would reduce dt 1 =dt 2  to a range between 0.1 s and 1.5 s-Δ. This means that the filling should be open to higher frequencies. Moreover, the two time windows for the functional and morphological data acquisition might be different from each other, and might be incremented or decremented by constant values, or even randomly, throughout the overall data acquisition sequence. 
     As noted above, the morphological sequence can be a sequence that is optimized to minimize acoustic noise, such as a sequence using radial or spiral trajectories for entering data into k-space, with minimized gradient slew rate and gradient vector angular speeds. 
     Likewise, the BOLD-EPI rsfMRI sequence may also use radial or spiral EPI sequences for the same purpose. Both optimizations are for the purpose of minimizing the acoustic impact on the patient, thereby improving comfort of the patient during the scan. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  schematically illustrates a magnetic resonance imaging (tomography) apparatus that is operable to implement the method according to the invention. 
         FIG. 2  schematically illustrates a conventional echo planar imaging (EPI) sequence for the acquisition of magnetic resonance data. 
         FIG. 3  schematically illustrates the entry of data into k-space, using the sequence shown in  FIG. 2 . 
         FIG. 4  schematically illustrates the principles of a gradient echo sequence for the acquisition of morphological magnetic resonance data. 
         FIG. 5  is a flowchart illustrating the principles of the MPRAGE sequence for acquiring morphological magnetic resonance data. 
         FIG. 6  schematically illustrates the interleaving of a functional magnetic resonance data acquisition sequence with a morphological magnetic resonance data acquisition sequence, in accordance with the present invention. 
     
    
    
     DESCRIPTION OF THE PREFERRED EMBODIMENTS 
       FIG. 1  shows a magnetic resonance system  5  (a magnetic resonance imaging (magnetic resonance tomography) apparatus). A basic field magnet  1  generates a temporally constant, strong magnetic field for polarization or alignment of the nuclear spins in an examination region of an examination subject U, for example of a part of a human body that is to be examined, which body lies on a table  23  and is slid into the magnetic resonance system  5 . The high homogeneity of the basic magnetic field that is required for the magnetic resonance measurement (data acquisition) is defined in a typically spherical measurement volume M into which the parts of the human body that are to be examined are introduced. Shim plates made of ferromagnetic material are attached at a suitable point to assist the homogeneity requirements, and in particular to eliminate temporally invariable influences. Temporally variable influences are eliminated by shim coils  2  and a suitable control  27  for the shim coils  2 . 
     A cylindrical gradient coil system  3  composed of three sub-windings is used in the basic field magnet  1 . Each sub-winding is supplied with current by a corresponding amplifier  24 - 26  to generate a linear gradient field in a respective direction of the Cartesian coordinate system. The first sub-winding of the gradient field system  3  generates a gradient G x  in the x-direction; the second sub-winding generates a gradient G y  in the y-direction; and the third sub-winding generates a gradient G z  in the z-direction. Each of the amplifiers  24 - 26  has a digital/analog converter (DAC), which is activated by a sequence controller  18  for accurately-timed generation of gradient pulses. 
     A radio-frequency antenna  4  that converts the radio-frequency pulses emitted by a radio-frequency power amplifier into an alternating magnetic field for excitation of the nuclei and alignment of the nuclear spins of the subject to be examined or of the region of the subject that is to be examined is located within the gradient field system  3 . The radio-frequency antenna  4  is composed of one or more RF transmission coils and one or more RF reception coils in the form of an annular, linear or matrix-like arrangement, for example. The alternating field emanating from the precessing nuclear spins—i.e. normally the nuclear spin echo signals caused by a pulse sequence composed of one or more radio-frequency pulses and one or more gradient pulses—is also converted by the RF reception coils of the radio-frequency antenna  4  into a voltage (measurement signal), which is supplied via an amplifier  7  to radio-frequency reception channels  8 ,  8 ′ of a radio-frequency system  22 . The radio-frequency system  22  furthermore has a transmission channel  9  in which the radio-frequency pulses are generated for the excitation of nuclear magnetic resonance. The respective radio-frequency pulses are digitally represented in the sequence controller  18  as a series of complex numbers based on a pulse sequence predetermined by the system computer  20 . This number sequence is supplied as a real part and imaginary part to a digital/analog converters (DAC) in the radio-frequency system  22  via respective inputs  12  and from said digital/analog converter (DAC) to the transmission channel  9 . In the transmission channel  9  the pulse sequences are modulated on a radio-frequency carrier signal having a base frequency that corresponds to the resonance frequency of the nuclear spins in the measurement volume. The modulated pulse sequences of the RF transmission coils are supplied to the radio-frequency antenna  4  via an amplifier  28 . 
     Switching from transmission operation to reception operation takes place via a transmission/reception diplexer  6 . The RF transmission coil of the radio-frequency antenna  4  radiates the radio-frequency pulses for excitation of the nuclear spins into the measurement volume M and scans resulting echo signals via the RF reception coils. The acquired nuclear magnetic resonance signals are phase-sensitively demodulated to an intermediate frequency in a first demodulator  8 ′ of the reception channel of the radio-frequency system  22  and are digitized in an analog/digital converter (ADC). This signal is further demodulated to a frequency of zero. The demodulation to a frequency of zero and the separation into real part and imaginary part occur in a second demodulator  8  after the digitization in the digital domain. The demodulator  8  supplies the demodulated data to an image computer  17  via outputs  11 . An MR image can be reconstructed by the image computer  17  from the measurement data acquired in such a manner. 
     The administration of the measurement data, the image data and the control programs takes place via the system computer  20 . The system computer  20  has a module to determine a phase shift of a measurement data set  20 . 1 , a module to calculate a relevant phase shift from determined phase shifts  20 . 2 , and a module to determine a B 1  distribution from a relevant phase shift  20 . 3 . The intermediate results (that arise in the processing of the measurement data in the system computer  20 ) and results—in particular specific B 1  distributions—can be stored and/or displayed for further use, for example in subsequent MR measurements. 
     Based on a specification with control programs, the sequence controller  18  monitors the generation of the respective desired pulse sequences and the corresponding scanning of k-space. In particular, the sequence controller  18  controls the time-accurate switching of the gradients, the emission of the radio-frequency pulses with defined phase amplitude and the reception of the nuclear magnetic resonance signals. The time base for the radio-frequency system  22  and the sequence controller  18  is provided by a synthesizer  19 . The selection of corresponding control programs to generate an MR image (which control programs are stored on a DVD  21 , for example) and other inputs on the part of the user (such as a desired frequency, in particular of non-resonant RF pulses) and a presentation of generated MR images take place via a terminal  13  that has input means to enable an input (for example a keyboard  15  and/or a mouse  16 ) and display means (a monitor  14 , for example) to enable a display. 
       FIG. 2  shows the characteristic features of an echo planar imaging (EPI) sequence, of the type used to acquire functional magnetic resonance data by means of the BOLD effect.  FIG. 3  schematically illustrates the entry of data into k-space, correlated with the sequence shown in  FIG. 2 . 
     In the embodiment of EPI shown in  FIG. 1 , an RF excitation pulse (which may be a 90 degree pulse as shown in  FIG. 2 ) is radiated, which can be made slice-selective by contemporaneous activation of a slice-selective gradient G f , which may also be used for frequency coding. An orthogonal gradient G P  is radiated for phase coding of the acquired signals. The imaging sequence is repeated multiple times for different values of the phase coding gradient G P . The resulting magnetic resonance signal is digitized and stored in each repetition of the sequence, in the presence of a readout gradient G R . A numerical matrix in k-space is thereby filled, as shown in  FIG. 3  in the case of a 2D k-space having directions k x  and k y . With an appropriate sequence, however, data may be entered into a 3D k-space matrix. 
     As shown in  FIG. 2 , multiple phase-coded echoes are used to fill the k-space matrix. The basis of this sequence is to generate a series of echoes in the readout direction (i.e., the direction of the readout gradient G R ) after a single, selective RF excitation. The echoes are associated by suitable modulation of the phase coding gradient G P  with different lines in k-space. 
     In the embodiment shown in  FIG. 2 , after the 90 degree RF excitation pulse and a refocusing pulse, multiple gradient echoes are generated by an oscillating frequency coding gradient in the readout direction. The phase coding in this embodiment ensues by means of small gradient pulses in the range of the zero crossing of the oscillating frequency coding gradient (shown on line AQ in  FIG. 1 ). This results in a serpentine data entry path (trajectory) in the spatial frequency domain represented by the k-space matrix shown in  FIG. 2 . It should be noted, however, that other EPI sequences can be used that result in spiral or radial scanning of k-space. 
     The aforementioned MPRAGE sequence, which is the preferred sequence for use in accordance with the present invention for morphological magnetic resonance image data acquisition, is a sequence in the family of sequences that are collectively referred to as gradient echo sequences. The basic characteristics of a gradient echo sequence are schematically illustrated in  FIG. 4 . In this pulse sequence, after the RF pulse, the signal is located in the center of k-space, as indicated at A. A de-phasing of the signal occurs at point B, due to the phase coding gradients and the de-phasing in the readout direction. A line of k-space is scanned, as indicated at C and D during the reverse-polarized readout gradients, and the signal is acquired. The gradient echo occurs at C. The entire process is repeated N x  times, with phase coding gradients of respectively different strengths, such that the entirety of k-space is filled with data (scanned). 
       FIG. 5  shows the basic principle of the MPRAGE sequence. This is based on the 3D Fourier technique as well as the magnetization preparation. A preparation phase is activated before the actual image phase, in order to achieve shorter measurement times and a good tissue contrast. The preparation phase effects a preparation of the magnetization that is dependent on the relaxation times T 1  and T 2 . The magnetization prepared in this manner is spatially coded and scanned using the gradient echo sequence shown in  FIG. 4 .  FIG. 5  schematically illustrates the workflow of the MPRAGE sequence, in which a magnetization preparation initially occurs, and in the imaging phase all Fourier lines are subsequently acquired in the x direction, given a constant value K z  along the z axis. A recovery phase follows for a better signal-to-noise ratio, and thus a better contrast, and the sequence is subsequently repeated for further values of k z , as indicated by the increment Δk. 
     The MPRAGE sequence is usually the sequence of choice for depiction of T 1 -weighted images of the head with good contrast between gray and white brain matters, and a good contrast between cerebrospinal fluid (CSF) and gray brain matter. 
       FIG. 6  schematically illustrates the method according to the invention, wherein a magnetic resonance apparatus of the type shown in  FIG. 1  is caused to operate to execute alternating rsfMRI sequences and morphological MRI sequences. Four such alternating sequences are shown in  FIG. 6 , but more may be implemented. Each sequence has a respective duration dt 1 , dt 2 , dt 3 , dt 4 , etc. It may be the case that all of these durations are equal, but it may also be the case that each duration is different, or incrementally or decrementally changing durations may be used, or randomly changing durations may be used. As noted above, preferably all durations are in a range between 0.1 s and 5 s-Δ, wherein Δ accounts for the bandwidth of the band-limited functional magnetic resonance information, with Δ=1 s, for example. If resting state modulations are found to occur at higher center frequencies, such as around 0.3 Hz, the durations may be in a range between 0.1 s and 1.5 s-Δ. 
     The magnetic resonance apparatus shown in  FIG. 1  is caused to execute the sequences shown in  FIG. 6  by virtue of programming instructions that are encoded on a storage medium, such as the DVD  21  shown in  FIG. 1 , which is loaded into the control unit represented by the terminal  13  in  FIG. 1 . 
     Although modifications and changes may be suggested by those skilled in the art, it is the intention of the inventors to embody within the patent warranted hereon all changes and modifications as reasonably and properly come within their scope of contribution to the art.