MR imaging using apt contrast enhancement and sampling at multiple echo times

Abstract

The invention relates to a method of CEST or APT MR imaging of at least a portion of a body (10) placed in a main magnetic field B.sub.0 within the examination volume of a MR device. The method of the invention comprises the following steps: •a) subjecting the portion of the body (10) to a saturation RF pulse at a saturation frequency offset; •b) subjecting the portion of the body (10) to an imaging sequence comprising at least one excitation/refocusing RF pulse and switched magnetic field gradients, whereby MR signals are acquired from the portion of the body (10) as spin echo signals; •c) repeating steps a) and b) two or more times, wherein the saturation frequency offset and/or a echo time shift in the imaging sequence are varied, such that a different combination of saturation frequency offset and echo time shift is applied in two or more of the repetitions; •d) reconstructing a MR image and/or B.sub.0 field homogeneity corrected APT/CEST images from the acquired MR signals. Moreover, the invention relates to a MR device (1) for carrying out the method of the invention and to a computer program to be run on a MR device.

Claims

1. A method of MR imaging of at least a portion of a body placed in a main magnetic field B.sub.0 within the examination volume of a MR device, the method comprising the following steps: a) subjecting the portion of the body to a saturation RF pulse at a saturation frequency offset respective to the resonance frequency of water protons; b) subjecting the portion of the body to an imaging sequence comprising excitation and refocusing RF pulses and switched magnetic field gradients, whereby MR signals are acquired from the portion of the body as spin echo signals; c) repeating steps a) and b) two or more times, wherein at least one of the saturation frequency offset and an echo time shift in the imaging sequence are varied, such that a different combination of saturation frequency offset and echo time shift is applied in two or more of the repetitions; d) reconstructing a MR image as B.sub.0 field homogeneity corrected amide proton transfer (APT)/Chemical Exchange Saturation Transfer (CEST) images from the acquired MR signals; wherein the reconstructing includes determining a spatial variation of B.sub.0 within the portion of the body from the acquired MR signals using a multi-point Dixon technique based on MR signal acquisitions with different saturation frequency offsets and different echo time shifts.

2. The method of claim 1 wherein the repeating of steps a) and b) includes repeating with a number of offset-values for the saturation frequency offset and a number of shift-values for the echo-time shift are selected and for each of the respective different selected offset-values a different shift value for the echo time shift is applied in the imaging sequence.

3. The method of claim 2, wherein the applied offset-values and the applied shift values effect a sparse sampling of a plane spanned by offset values and shift values.

4. The method of claim 1, wherein the spatial variation of B.sub.0 within the portion of the body is determined from the acquired MR signals using the multi-point Dixon technique based on the MR signal acquisitions with the different saturation frequency offsets that are positive with respect to the resonance frequency of water protons.

5. The method of claim 1, wherein the reconstruction of the MR image includes deriving a spatial distribution of amide protons within the portion of the body from an asymmetry analysis of the amplitude of the acquired MR signals as a function of the saturation frequency offset respective to the resonance frequency of water protons, which asymmetry analysis involves a saturation frequency offset correction based on the determined spatial variation of B.sub.0.

6. The method of claim 5, wherein the reconstruction of the MR image includes deriving a spatial pH distribution within the portion of the body from an asymmetry analysis of the amplitude of the acquired MR signals as a function of the saturation frequency offset respective to the resonance frequency of water protons, which asymmetry analysis involves a saturation frequency offset correction based on the determined spatial variation of B.sub.0.

7. The method of claim 1, wherein saturation RF pulses are applied in different repetitions of steps a) and b) at positive and negative saturation frequency offsets around the resonance frequency of water protons.

8. The method of claim 1, wherein steps a) and b) are repeated two or more times with the same saturation frequency offset and with a different echo time shift in two or more of the repetitions.

9. The method of claim 1, wherein steps a) and b) are repeated two or more times with a different saturation frequency offset and with a different echo time shift in two or more of the repetitions.

10. The method of claim 1, wherein the repeating of steps a) and b) generates exactly one combination of saturation frequency offset and echo time shift for each saturation frequency offset.

11. The method of claim 1, wherein the determining of the spatial variation of B.sub.0 within the portion of the body produces a single B.sub.0 map which is used in the B.sub.0 field homogeneity correction of all of the B.sub.0 field homogeneity corrected APT/CEST images.

12. A magnetic resonance (MR) device comprising: at least one main magnet coil for generating a uniform, steady magnetic field within an examination volume; a number of gradient coils for generating switched magnetic field gradients in different spatial directions within the examination volume; at least one RF coil for generating RF pulses within the examination volume and/or for receiving MR signals from a body of a patient positioned in the examination volume; and a computer programmed to control the temporal succession of RF pulses generated by the at least one RF coil and switched magnetic field gradients generated by the gradient coils and to reconstruct an MR image from the received MR signals by performing the following steps: a) subjecting the portion of the body to a saturation RF pulse generated by the at least one RF coil at a saturation frequency offset with respect to the resonance frequency of water protons; b) subjecting the portion of the body to an imaging sequence comprising excitation and refocusing RF pulses generated by the at least one RF coil and switched magnetic field gradients generated by the gradient coils, whereby MR signals are acquired from the portion of the body as spin echo signals; c) repeating steps a) and b) two or more times, wherein at least one of the saturation frequency offset and an echo time shift in the imaging sequence are varied, such that a different combination of saturation frequency offset and echo time shift is applied in two or more of the repetitions; d) reconstructing an MR image as B.sub.0 field homogeneity corrected amide proton transfer (APT)/Chemical Exchange Saturation Transfer (CEST) images from the acquired MR signals; wherein the reconstructing includes determining a spatial variation of B.sub.0 within the portion of the body from the acquired MR signals using a Dixon technique based on MR signal acquisitions with different saturation frequency offsets and different echo time shifts to produce a single B.sub.0 map which is used in the B.sub.0 field homogeneity correction of all of the B.sub.0 field homogeneity corrected APT/CEST images.

13. A non-transitory data carrier storing a computer program to be run on a magnetic resonance (MR) device, which computer program comprises instructions for causing the MR device to perform a method including: a) generating a saturation RF pulse at a saturation frequency offset with respect to the resonance frequency of water protons; b) generating an imaging sequence comprising excitation and refocusing RF pulses and switched magnetic field gradients, whereby MR signals are acquired from the portion of the body as spin echo signals; c) repeating steps a) and b) two or more times, wherein at least one of the saturation frequency offset and an echo time shift in the imaging sequence are varied, such that a different combination of saturation frequency offset and echo time shift is applied in each of the two or more of the repetitions and the repetitions generate exactly one combination of saturation frequency offset and echo time shift for each saturation frequency offset; d) reconstructing an MR image as B.sub.0 field homogeneity corrected amide proton transfer (APT)/Chemical Exchange Saturation Transfer (CEST) images from the acquired MR signals; wherein the reconstructing includes determining a spatial variation of B.sub.0 within the portion of the body from the acquired MR signals using a Dixon technique based on MR signal acquisitions with different saturation frequency offsets and different echo time shifts.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) The enclosed drawings disclose preferred embodiments of the present invention. It should be understood, however, that the drawings are designed for the purpose of illustration only and not as a definition of the limits of the invention. In the drawings:

(2) FIG. 1 shows a MR device according to the invention;

(3) FIG. 2 shows a diagram illustrating the scheme of saturation frequency offsets used for APT MR imaging according to the invention,

(4) FIG. 3 shows a diagram illustrating a first embodiment of the APT acquisition scheme according to the invention;

(5) FIG. 4 shows a diagram illustrating a second embodiment of the APT acquisition scheme according to the invention.

DETAILED DESCRIPTION OF THE EMBODIMENTS

(6) With reference to FIG. 1, a MR device 1 is shown. The device comprises superconducting or resistive main magnet coils 2 such that a substantially uniform, temporally constant main magnetic field B.sub.0 is created along a z-axis through an examination volume. The device further comprises a set of (1.sup.st, 2.sup.nd, and—where applicable—3.sup.rd order) shimming coils 2′, wherein the current flow through the individual shimming coils of the set 2′ is controllable for the purpose of minimizing B.sub.0 deviations within the examination volume.

(7) A magnetic resonance generation and manipulation system applies a series of RF pulses and switched magnetic field gradients to invert or excite nuclear magnetic spins, induce magnetic resonance, refocus magnetic resonance, manipulate magnetic resonance, spatially and otherwise encode the magnetic resonance, saturate spins, and the like to perform MR imaging.

(8) More specifically, a gradient pulse amplifier 3 applies current pulses to selected ones of whole-body gradient coils 4, 5 and 6 along x, y and z-axes of the examination volume. A digital RF frequency transmitter 7 transmits RF pulses or pulse packets, via a send-/receive switch 8, to a body RF coil 9 or to a set of local array RF coils 11, 12, 13, to transmit RF pulses into the examination volume. A typical MR imaging sequence is composed of a packet of RF pulse segments which, together with any applied magnetic field gradients, achieve a selected manipulation of nuclear magnetic resonance. The RF pulses are used to saturate, excite resonance, invert magnetization, refocus resonance, or manipulate resonance and select a portion of a body 10 positioned in the examination volume. The MR signals are also picked up by the body RF coil 9.

(9) For generation of MR images of limited regions of the body 10 by means of parallel imaging, a set of local array RF coils 11, 12, 13 are placed contiguous to the region selected for imaging. The array coils 11, 12, 13 can be used to receive MR signals induced by body-coil RF transmissions.

(10) The resultant MR signals are picked up by the body RF coil 9 and/or by the array RF coils 11, 12, 13 and demodulated by a receiver 14 preferably including a preamplifier (not shown). The receiver 14 is connected to the RF coils 9, 11, 12 and 13 via send-/receive switch 8.

(11) A host computer 15 controls the shimming coils 2′ as well as the gradient pulse amplifier 3 and the transmitter 7 to generate any of a plurality of MR imaging sequences, such as echo planar imaging (EPI), echo volume imaging, gradient and spin echo imaging, fast spin echo imaging, and the like. For the selected sequence, the receiver 14 receives a single or a plurality of MR data lines in rapid succession following each RF excitation pulse. A data acquisition system 16 performs analog-to-digital conversion of the received signals and converts each MR data line to a digital format suitable for further processing. In modern MR devices the data acquisition system 16 is a separate computer which is specialized in the acquisition of raw image data.

(12) Ultimately, the digital raw image data are reconstructed into an image representation by a reconstruction processor 17 which applies a Fourier transform or other appropriate reconstruction algorithms, such as SENSE or GRAPPA. The MR image may represent a planar slice through the patient, an array of parallel planar slices, a three-dimensional volume, or the like. The image is then stored in an image memory where it may be accessed for converting slices, projections, or other portions of the image representation into appropriate format for visualization, for example via a video monitor 18 which provides a man-readable display of the resultant MR image.

(13) In accordance with the invention, the portion of the body 10 is subjected to saturation RF pulses at different saturation frequency offsets prior to acquisition of MR signals by means of a spin echo sequence, which is preferably a fast spin echo (FSE) or turbo spin echo (TSE) sequence or a related pulse sequence like GRASE (a combined spin echo and gradient echo sequence). The saturation RF pulses are irradiated via the body RF coil 9 and/or via the array RF coils 11, 12, 13, wherein the saturation frequency offset relative to the MR frequency of water protons is set by appropriate control of the transmitter 7 via the host computer 15. As shown in FIG. 2, different saturation frequency offsets are applied around +/−3.5 ppm around the MR frequency of water protons (0 ppm). The different saturation frequency offsets are indicated by black arrows in FIG. 2. A further reference acquisition may be performed “off-resonant”, i.e. with a very large frequency offset which leaves the MR signal amplitude of water protons unaffected or with the RF saturation power switched off, which is useful for signal normalization (quantification of the z-spectral asymmetry). This is indicated by the leftmost black arrow in FIG. 2.

(14) According to the invention, MR signal acquisition steps are repeated several times, wherein the saturation frequency offset and the echo time shifts in the spin echo sequence are varied, such that a different combination of saturation frequency offset and echo time shift is applied in two or more of the repetitions. Finally, an APT/CEST MR image is reconstructed from the acquired MR signals. This means that the reconstruction of the MR image includes deriving the spatial distribution of amide protons within the portion of the body 10 from an asymmetry analysis or a similar z-spectral analysis technique base on the amplitude of the acquired MR signals as a function of the saturation frequency offset. This z-spectral analysis, which is conventionally applied in APT/CEST MR imaging, is very sensitive to any inhomogeneity of the main magnetic field B.sub.0. This is taken into account by the method of the invention by determination of the spatial variation of B.sub.0 from the acquired MR signals by means of a multi-point Dixon technique. The determined spatial variation of B.sub.0 is then used for a corresponding saturation frequency offset correction in the asymmetry analysis or other z-spectral analysis technique.

(15) For a determination of the spatial variation of B.sub.0, two specific strategies may be applied in accordance with the invention. These strategies are illustrated in the diagrams of FIGS. 3 and 4.

(16) The saturation steps are indicated in FIGS. 3 and 4 by SAT−3, SAT−2, SAT-1, SAT0, SAT+1, SAT+2 and SAT+3. Therein, SAT−1, SAT−2 and SAT−3 correspond to negative saturation frequency offsets, while SAT+1, SAT+2 and SAT+3 correspond to positive saturation frequency offsets. SAT0 corresponds to a reference measurement, in which an off-resonant frequency offset is applied, as mentioned above. ACQ1, ACQ2, ACQ3 and ACQ4 indicate MR signal acquisition steps using different echo time shifts (TE.sub.1, TE.sub.2, TE.sub.3, TE.sub.4), respectively.

(17) In the embodiment shown in FIG. 3, an acquisition with any saturation frequency offset SAT−3, SAT−2, SAT−1, SAT0, SAT+1, SAT+2 and SAT+3 is repeated three times, each with a different echo time shift, indicated by ACQ1, ACQ2, and ACQ3. This results in an overall number of 21 repetitions. B.sub.0 mapping is preferably performed separately for each saturation frequency offset.

(18) In the further embodiments shown FIG. 4, the acquisitions with different saturation frequency offsets SAT−3, SAT−2, SAT−1, SAT+1, SAT+2, SAT+3 are performed only once, but with different echo time shifts, indicated by ACQ1, ACQ2, ACQ3 and ACQ4 (echo times TE.sub.1, TE.sub.2, TE.sub.3, TE.sub.4). ACQ0 indicates an acquisition without echo time shift (echo time TE.sub.0). A multi-point (iterative) Dixon technique is applied to derive the B.sub.0 map from these acquisitions combining the data from different saturation frequency offsets, according to the invention. In FIG. 4a three different echo time shifts (indicated by ACQ1, ACQ2, ACQ3) are applied with the saturation frequency offsets SAT+1, SAT+2 and SAT+3. The B.sub.0 map is derived from these acquisitions. No echo time shift is applied in the acquisitions with SAT−3, SAT−2, SAT−1 and SAT0. The B.sub.0 map is applied for correction in these acquisitions. In FIG. 4b the different echo time shifts are also applied with SAT−3, SAT−2, SAT−1. No echo time shift is applied for SAT0. In FIG. 4c three different echo time shifts (that are well-suited for 3-point Dixon B.sub.0 mapping) are applied with saturation frequency offsets SAT+1, SAT+2, SAT+3, while a single echo time shift that is well-suited for water/fat separation (indicated by ACQ4) is applied with saturation frequency offsets SAT0, SAT−1, SAT−2 and SAT−3. In FIG. 4d no echo time shift is applied for SAT−3, SAT−2, SAT−1 and SAT+1, SAT+2, SAT+3, while three different echo time shifts are applied with SAT−0 (for B.sub.0 mapping).

(19) For positive saturation frequency offsets which are placed in close spectral proximity of the chemical shift of the exchangeable proton pool in question (e.g. +3.5 ppm for APT), the MR signal amplitude of water protons is expected to vary slightly (<10%) between the individual acquisitions due to different extents of direct saturation of water protons and due to the relevant saturation transfer effects, as mentioned above. The resulting signal variation may be addressed in different ways for the purpose of B.sub.0 mapping. One option is to simply ignore this small signal variation. This option can be used in practice, in particular in combination with specifically positioned saturation frequency offsets, but it may potentially result in a somewhat reduced precision of the determined B.sub.0 map. Another option is to minimize the influence of the signal variations by choosing appropriate echo time shifts, where the Dixon-based B.sub.0 determination is most robust against signal variations. A further option is to apply an appropriate mathematical model of the acquired composite complex MR signals and to derive the B.sub.0 from the resulting model parameters. Different strategies for MR signal modeling in Dixon imaging exist, which can be applied in accordance with the invention, and which are per se known in the art.

(20) In an embodiment of the invention, the composite complex signal S acquired with SAT+1, SAT+2, SAT+3 may be modeled by:
S.sub.+1=(W.sub.1+c.sub.1F)PΔP*
S.sub.+2=(W.sub.2+c.sub.2F)P
S.sub.+3=(W.sub.3+c.sub.3F)PΔP
or, by using a linear approximation, as:
S.sub.+1=(W−ΔW+c.sub.1F)PΔP*
S.sub.+2=(W+c.sub.2F)P
S.sub.+3=(W+ΔW+c.sub.3F)PΔP,
wherein W denotes the water signal contribution, F denotes the fat signal contribution, P and ΔP denote phase errors, and c denotes coefficients that describe the amplitude and phase of a unit fat signal at the respective echo time shift. W, F, P, and ΔP are considered as unknowns, while S and c are considered as knowns. In the first case (without approximation), the number of knowns (real and imaginary components of S) and the number of unknowns (real W.sub.1-W.sub.3, real F, phase of P and ΔP) are both equal to six. In the second case (with approximation), the number of knowns exceeds the number of unknowns by one. The acquisition with saturation frequency offset SAT0 may be included as fourth equation, again with a different W and the same F. B.sub.0 can be derive on a voxel-by-voxel basis from the resulting model parameters.

(21) The spatial variation of B.sub.0 can be assumed not to change between the individual MR signal acquisition steps to acquire the different saturation frequency offsets for APT/CEST MRI. Accordingly, once the spatial variation of B.sub.0 has been determined in the afore-described manner, the obtained B.sub.0 map can be used for suppression of signal contributions from fat spins. A Dixon method can be applied to perform a water/fat separation after demodulation of B.sub.0-induced phase errors. The echo time values can be optimized to maximize the signal-to-noise ratio in the resulting water MR images, for instance by choosing echo time shifts at which signal contributions from water and fat spins are in quadrature, i.e. 90° out of phase. If other echo time values are preferred for B.sub.0 mapping than are favorable for Dixon water/fat separation, some acquisitions with appropriate saturation frequency offsets may be repeated with correspondingly chosen echo time values.

(22) For positive saturation frequency offsets, one of the schemes illustrated in FIG. 4 for obtaining the B.sub.0 map can also be employed to suppress signal contributions from fat spins. For the acquisitions with negative saturation frequency offsets near the chemical shift of fat protons, the extent of saturation of fat protons imposed by the saturation RF pulses can be modeled on the basis of an appropriate mathematical model, taking the RF pulse parameters (for example shape, bandwidth) and the spectrum of the fat protons (for example number of peaks, resonance frequencies, resonance areas, line widths) into account.

(23) In an exemplary embodiment, the composite signal S acquired with SAT−1, SAT−2, SAT−3 may be modeled as:
S.sub.−1=(W.sub.1+c.sub.1d.sub.1F)PΔP*
S.sub.−2=(W.sub.2+c.sub.2d.sub.2F)P
S.sub.—3=(W.sub.3+c.sub.3d.sub.3F)PΔP
or, using a linear approximation, as:
S.sub.−1=(W−ΔW+c.sub.1d.sub.1F)PΔP*
S.sub.−2=(W+c.sub.2d.sub.2F)P
S.sub.−3=(W+ΔW+c.sub.3d.sub.3F)PΔP,
wherein d denotes coefficients that describe the relative extent of fat suppression. For the acquisitions with both, positive and negative saturation frequency offsets, F may be considered as unknown, or F may be considered as known from the water/fat separation in the acquisition with off-resonant saturation SAT0.

(24) After water/fat separation, an APT/CEST MR image at the desired saturation offset frequency (e.g. +3.5 ppm for APT) can be reconstructed by means of the above-mentioned asymmetry analysis or other z-spectral analysis technique based on the voxel-wise amplitude of the water MR images as a function of the saturation frequency offset. Therein, the asymmetry/z-spectral analysis involves a saturation frequency offset correction based on the determined spatial variation of B.sub.0, e.g. by means of a voxel-by-voxel Lagrange interpolation of the images taken at different saturation frequency offsets.