Patent Description:
Quantitative MRI (qMRI) plays an important role in the study of tissue- and organ-specific pathologies and has been widely adopted to support diagnosis, monitor therapy and interventions in many clinical applications. The main goal of qMRI techniques is to estimate tissue-specific parameters with minimal experimental bias. The estimation of an "absolute" MR tissue property has high interest because it may allow to detect pathological tissue as well as it could be used to follow-up pathological conditions for a single patient, compare patient groups, or compare single patient outcomes to normative values. Additionally, the measure of tissue properties is sought to be independent of the scanner hardware being used.

Conventional qMRI methods use analytical solutions of spin evolutions to estimate tissue properties (e.g., T1 and T2 relaxation parameters in MRI). These techniques typically implement a series of inversion- or saturation-recovery measurements to estimate the longitudinal (spin-lattice) relaxation time, T1, and spin-echo measurements to estimate the transverse (spin-spin) relaxation time, T2. Although such measurements can provide excellent results and are often used as ground-truth, they require long acquisition times (TA) that are impractical for use in routine clinical examinations. Therefore, alternative methods have been introduced to determine T1 and T2 more rapidly. However, high isotropic spatial resolution and large volume coverage are still limited by long TA and/or signal-to-noise-ratio. Additionally, most of these methods are tailored to estimate a single MR parameter at a time and, in turn, their results are often biased by physical mechanisms that are not accounted for in the model.

Over the last two decades, research has focused on qMRI techniques to simultaneously estimate T1 and T2 for increased accuracy and reduced experimental bias and acquisition time. In particular, a first method, DESPOT1/<NUM> by Deoni et al. [<NUM>], uses variable flip angles to drive longitudinal and transversal magnetization to steady state with a spoiled gradient echo sequence to estimate T1 and subsequently with a steady-state free precession sequence for T2. While DESPOT1/<NUM> is faster than conventional methods and offers high signal-to-noise ratio, its analytical solution may still suffer from experimental bias. A second method, called MR fingerprinting (MRF), had an important impact in the MRI community (Ma et al. [<NUM>], <CIT>). MRF introduced a paradigm shift from steady-state sequences to transient states achieved by continuously changing sequence parameters and, therefore, from analytical solutions to physics-based numerical models of those unique signal evolutions. By doing so, MRF deliberately entangles relaxation parameters evolution with unique experimental conditions and uses dictionary fitting to estimate tissue properties. The many degrees of freedom of MRF enable fast and simultaneous estimation of tissue properties. However, accuracy of such estimates may be limited by experimental factors mainly related to the nonconventional fast sequences used for the acquisition.

Another technique relevant for the present invention is the magnetization-prepared rapid gradient echo (MPRAGE) technique [<NUM>]. In this context, two methods for estimating T1 and T2 independently are of particular relevance:.

The conference abstract [<NUM>] describes a method of using T2 preparation using adiabatic pulses in conjunction with a segmented FLASH sequence to obtain uniform whole-brain T2 weighting and perform a T2 mapping.

It is an objective of the present invention to find a system and method capable of simultaneously mapping MRI parameters such as T1, T2, and other tissue- or system-specific parameters like proton density or field inhomogeneity that overcome the above-mentioned disadvantages (i.e. notably limitations in accuracy, acquisition time, and experimental bias) and are suitable for clinical applications.

Said objective is achieved according to the present invention by a system and method for simultaneous mapping of qMRI parameters using a T2 prepared inversion according to the object of the independent claims. Dependent claims present further advantages of the invention.

The present invention proposes notably and in accordance with claim <NUM> a qMRI method for mapping one or several qMRI parameters of a biological object with an MRI system, capable of simultaneously mapping several of said qMRI parameters, the method comprising the following steps:.

In other words, the invention proposes thus a qMRI method using a novel magnetization prepared rapid gradient echo approach coupled preferentially with a dictionary matching method for quantitative parameter maps reconstruction. Contrary to the first method described above, i.e. said MP2RAGE sequence which uses a simple inversion for its magnetization preparation module, the present invention proposes to use a modified T2-prepared inversion module (T2pi) to invert the longitudinal magnetization while encoding T2 contrast in the subsequent T1 recovery. Contrary to said second method, i.e. said T2PRAGE sequence, the present invention proposes to use two or more readouts, and not only one.

The present invention concerns also an MRI system or apparatus configured for simultaneous mapping of one or several qMRI parameters of a biological object by carrying out the steps of the previously described method.

The foregoing has broadly outlined the features and technical advantages of the present disclosure so that those skilled in the art may better understand the detailed description that follows.

Additional features and advantages of the disclosure will be described hereinafter that form the object of the claims. Those skilled in the art will appreciate that they may readily use the concept and the specific embodiment disclosed as a basis for modifying or designing other structures for carrying out the same purposes of the present disclosure.

For a more complete understanding of the present disclosure, and the advantages thereof, reference is now made to the following descriptions taken in conjunction with the accompanying drawings, wherein like numbers designate like objects, and in which:.

<FIG> schematically shows known in the art pulse sequences, which are an MP2RAGE pulse sequence (A) and a T2PRAGE pulse sequence (B) which have been described respectively with the so-called first method and second method. These pulse sequences are known in the art sequences and do not need further description here.

<FIG> schematically illustrates an MRI system <NUM> according to the invention. As known in the art, said MRI system <NUM> comprises different coils <NUM> and respective coil controllers configured for generating magnetic fields and RF pulses in order to acquire an MRI signal from a biological object <NUM>. Said MRI signal is transmitted by a receiver coil controller to a processing unit <NUM> comprising typically a memory <NUM> and connected to a display <NUM> for displaying images reconstructed from the received MRI signal. Contrary to prior art MRI systems, the MRI system <NUM> according to the invention is configured for carrying out the following method described in connection with <FIG>.

At step <NUM>, the MRI system <NUM> performs one or several scans C_j, with j = <NUM>,. ,N, of the biological object <NUM>. For each scan, the MRI system <NUM> performs, at step <NUM>, one or several T2-prepared inversion pulse series characterized each by an echo time, i.e. inter-pulse duration, TEp_j, wherein said inter-pulse durations are different within a same scan and/or for each scan. An example of a T2-prepared inversion pulse sequence is provided by <FIG> showing one repetition time TR <NUM> of said sequence. The T2-prepared inversion module <NUM> (or pulse series) comprises notably a first pulse that is a tip-down RF pulse <NUM>, e.g. a rectangular tip-down RF pulse, followed by two successive refocusing pulses <NUM>, e.g. hyperbolic-secant adiabatic refocusing pulses, and ended with a fourth pulse that is also a tip-down RF pulse <NUM>, preferentially a rectangular one. The inter-pulse duration TEp_j is measured from the middle of the first pulse width until the middle of the fourth pulse width. A scan comprises multiple TR's to acquire an image. As explained previously, the present invention can be implemented as multiple scans each with a different echo time preparation TEp_j or with one single scan that comprises different echo time preparations TEp_j. In the preferred embodiment shown in <FIG>, the case of multiple scans is taken as illustration.

After performing said T2-prepared inversion module <NUM>, the MRI system <NUM> launches, at step <NUM>, an acquisition of an MRI recovery signal generated by at least a part of the biological object <NUM>. For this purpose, it is configured for generating, for said scan C_j and at different inversion times TI_i,j, with i=<NUM>,. ,M_j with M_j ≥ <NUM>, and before starting a next scan, M_j readout <NUM>, <NUM> RF excitation pulse sequences configured for applying a RF magnetic field B1 to said part of the biological, and for detecting and acquiring for each of said M_j readout excitation pulse sequences, thus for each of said different inversion times TI_i,j and in response to the application of said RF magnetic field B1, an MRI recovery signal S_i,j. In particular, each inversion time defines the time interval between the end of the T2-prepared inversion module <NUM> and the start of the corresponding readout RF excitation pulse sequence, i.e. readout block. The latter is for instance a segmented 3D MRI pulse sequence (e.g., FLASH [<NUM>]) employing an accelerated k-space sampling pattern [<NUM>]. A non-limiting illustration of an acquisition of said MRI recovery signal is shown in <FIG>, wherein two readout blocks, i.e. M_j=<NUM>, are acquired in each repetition time interval TR at different inversion times TI_1,j and TI_2,j after the T2-prepared inversion pulse sequence <NUM>. For each of said readout blocks, a center-out radial k-space ordering is used for encoding the prepared T2 contrast at the center of k-space. As known in the art, the slice-select gradient GSS, the in-plane phase-encoding gradient GPE and the readout (frequency-encoding) gradient GRO are controlled according to the specific type of readout block that is used, e.g. FLASH.

<FIG> illustrates a case where four scans C_j (i.e. N=<NUM>) were temporally successively performed, preferentially with the pulse sequence shown in <FIG>, i.e. with M_j=M=<NUM> readout blocks <NUM>, <NUM> for j=<NUM>,. ,N, i.e. according to a first inversion time TI<NUM> and a second inversion time TI<NUM>. Each scan C_j, with j=<NUM>,. ,<NUM> combines thus different TEp's and TI's to probe a wide range of T2 and T1 contrasts. In particular, scan C_1 and C_2 use short echo times TEp, with TEp_<NUM><TEp_<NUM> with shortest possible inversion times TI_1,<NUM> and TI_1,<NUM> and medium long second inversion times TI_2,<NUM> and TI_2,<NUM>, i.e. TI_2,<NUM> > TI_1,<NUM> and TI_2,<NUM> > TI_1,<NUM>, with for instance TI_1,<NUM> = TI_1,<NUM> and TI_2,<NUM> = TI_2,<NUM>. Scan C_3 and C_4 uses longer echo times TEp, i.e. with TEp_<NUM> < TEp_<NUM> < TEp_<NUM>, shortest possible first inversion time, e.g. TI_1,<NUM> = TI_1,<NUM> = TI_1,<NUM> and a longer second inversion time, i.e. TI_2,<NUM> > TI_2,<NUM> and TI_2,<NUM> > TI_2,<NUM>, or TI_2,<NUM> > TI_2,<NUM> and TI_2,<NUM> > TI_2,<NUM>, with preferentially TI_2,<NUM> = TI_2,<NUM>. In particular, TI_2,<NUM> and TI_2,<NUM> are strictly greater than any of the inversion times TI_2,<NUM> and TI_2,<NUM>, which are also strictly greater than any of the inversion times TI_1,<NUM>, TI_1,<NUM>, TI_1,<NUM>, and TI_1,<NUM>.

At step <NUM>, the MRI system, for instance its processing unit <NUM>, is configured for reconstructing, from each received MRI signal S_i,j, an image I_i,j of the biological object part under investigation. For instance, each scan C_1,. ,C_4 shown in <FIG> provides two 3D images, respectively one image at the first inversion time TI<NUM> and another image at the second inversion time TI<NUM>, resulting in overall eight images with different T<NUM> and T<NUM> weighting. Each image might be reconstructed using a compressed sensing algorithm [<NUM>]. Of course, other known in the art fast reconstruction methods or algorithm may also be suited for individual image reconstruction (e.g., parallel imaging, AI based, machine learning- or deep learning-based implementation, etc).

Preferentially, to account for biases due to B1 transmit field inhomogeneities, an additional, fast B1+ map might be acquired by the MRI system according to the invention.

At step <NUM>, the MRI system creates a voxel-wise signal from the intensity values that are provided by the different reconstructed images for a same voxel. Preferentially, said intensity values are concatenated to obtain said voxel-wise signal. In other words, the MRI system is configured for collecting, in each reconstructed image, the intensity value that is associated to the voxel that represents the same position within the imaged part of said biological object (i.e. for each voxel of a reconstructed image, the intensity value associated to the concerned voxel in said reconstructed image and the intensity value associated to the same voxel in all other reconstructed images are collected and associated to said voxel, i.e. to a position within the imaged part). This enables to construct or create, for each voxel, said voxel wise signal <NUM> as shown in <FIG>. The latter associates to each couple of time values (TEp_j,TI_i,j) <NUM>, i.e. to each image, the intensity value <NUM> that has been obtained for the considered voxel in that image, i.e. for that couple of time values. Preferentially, the MRI system might automatically concatenate the intensity values <NUM> to obtain said voxel-wise signal <NUM>.

At step <NUM>, the MRI system, preferentially its processing unit, or another processing unit not part of the MRI system, e.g. a stand-alone computer, is configured for fitting a physical model to the concatenated intensity values <NUM> to obtain at least one quantitative map. For instance, the MRI system might be configured for performing a numerical simulation of each scan C_j, more precisely, of each of the voxel-wise acquired signals. This might be performed before step <NUM>, i.e. before starting the scanning process, or during the scanning process. Said numerical simulation is configured for generating, for each of said voxels, a set of simulated voxel-wise signals, associating, to each of said simulated voxel-wise signals, a value for one or several qMRI parameters, e.g. the corresponding value for T1, T2, B1+ for the considered voxel. Said set of simulated voxel-wise signals might populate a "dictionary" that can be used for imaging said biological part. In particular, different algorithms or physics-based models for estimating the qMRI parameters and simulating the acquired voxel-wise signals might be used, like EPG or conventional Bloch equations simulation.

Then, the MRI system, preferentially its processing unit or said another processing unit, might be configured for performing a reconstruction, for at least one of said qMRI parameters, of a quantitative map representing said part of the biological object. For generating said quantitative map, the processing unit is configured for matching, for each voxel of the quantitative map, the created voxel-wise signal defined for that voxel and all simulated voxel-wise signals generated for that voxel, and assigning to the considered voxel in said quantitative map the value of said at least one qMRI parameter for which the best match has been obtained. The obtained quantitative MRI map might then be displayed on the display <NUM>.

Preferentially, said fast B1+ map might be used for selecting the simulated voxel-wise signals which are associated to B1+ values that match the acquired B1+ value for the considered voxel. In particular, "matching" means that the difference between the intensity values of the acquired voxel wise signal or acquired parameter (e.g. B1+) and the intensity values of the simulated voxel wise signal or simulated parameter (e.g. B1+) is smaller than a predefined value. It has to be understood that different known techniques might be used for finding the best match between the simulated voxel-wise signals and the acquired one, for instance by using dot-product, RMSE, etc..

In general, the invention preferentially comprises at least <NUM>, but up to N scans with different TEp and at least two but up to M_j readout blocks for each scan C_j, with different TIs, where M_j, N, TEp's, and TIs are optimized to trade off accuracy of target T1 and T2 ranges with acquisition time. Thanks to the present invention, T1 and T2 maps might be simultaneously estimated/reconstructed from the voxel-wise "dictionary fitting" using the resulting magnitude images and optionally the B1+ map. In alternative to dictionary fitting, a model-based approach, which employs a physics model within the reconstruction, can be used to obtain quantitative maps directly from the acquired k-space.

To summarize, the present invention proposes a combination of a T2-prepared inversion module (or pulse sequence), notably the use of a tip-down/refocusing/tip-down pulse series, with a segmented readout sequence that includes multiple readout blocks following the magnetization preparation, i.e. said T2-prepared inversion pulse module. Using arbitrary combinations of T2 preparation (TEp times) and inversion times result in images whose contrast depend on both T1 and T2. Finally, these images can be used as input to an algorithm that construct said voxel-wise signal for each voxel and compares the latter to simulated voxel-wise signals which are each associated to qMRI parameters like T1 or T2 in order to construct a quantitative map of said qMRI parameter(s) from the best matching. This enables notably to construct simultaneously a T1 and T2 quantitative map.

Compared to T1 or T2 quantification techniques like MP2RAGE or T2-prepared rapid gradient echo sequences that estimate one relaxation parameter at the time, the advantage of the present invention is that it makes possible to include both T1 and T2 relaxation parameters in the signal model, minimizing therefore measurement bias from relaxation mechanisms different than the one being probed. Compared to other simultaneous T1/T2 quantification techniques like DESPOT1/<NUM> or MRF, the advantage of the invention consists of using a simple signal model and a conventional acquisition technology (e.g., Cartesian k-space sampling, magnetization preparation, FLASH readout sequences) that is well supported by current scanner hardware, readily available for clinical use and, more specifically, well suited for high isotropic resolution imaging with large volumetric coverage.

Advantageously, the proposed method further provides a lower sensitivity to B1+ inhomogeneity than the above-mentioned known in the art techniques, because of the low flip-angle readout out blocks, and a lower SAR compared to other T2 mapping methods like MESE based methods.

Without departing from the general concept of the present invention, different radio-frequency pulses for the T2-prepared inversion pulse sequence can be used, as long as said T2-prepared pulse sequence performs a T2-weighted inverted longitudinal magnetization before the readout blocks. Therefore, different adiabatic pulses like AFP, BIR4, etc., might be used for the tip-down or the refocusing in the T2-prepared inversion pulse sequence. In general, T2-prepared inversion scans could also be combined with conventional T2-prepared scans that employ tip-down/refocusing/tip-up pulse series using short or long inter-pulse duration TEp.

Also, different qMRI parameters, other than or in addition to T1, T2, can be probed by modifying the T2-prepared inversion pulse sequence and then subsequently estimated in the reconstruction, like relaxation times T1ρ, T2ρ, magnetization transfer, diffusion, B1+, perfusion, fat and/or water fraction, etc. In particular, T2' relaxation time could be estimated with the proposed invention by using a modified T2-preparation where the timings of the refocusing pulses are changed and made asymmetrical with respect to the middle of the tip-down inter-pulse duration (i.e. resulting in an uncomplete refocusing of the transverse magnetization), for instance for two refocusing pulses, by setting their timings at TEp/<NUM> and TEp/<NUM> (uncomplete refocusing) instead of TEp/<NUM> and <NUM>*TEp/<NUM> (refocused).

Similarly, while the described method proposes to an additional B1+ map to mitigate bias from transmit field inhomogeneity, other maps might be used to take other effects into account if necessary, like B1-, B0 frequency offset, diffusion, etc..

Preferentially, for the k-space sampling, the proposed method uses a variable-density Cartesian trajectory based on the spiral phyllotaxis pattern [<NUM>] and undersampled in phase-and slice-encoding dimensions. Of course, other k-space sampling strategies might be used, like hybrid Cartesian-radial trajectories like stack-of-stars, "kooshball" 3D radial, 2D spiral, 3D variable density "cones" spirals, etc. In particular, different k-space ordering than the radial-like previously described can be used.

Advantageously, the method according to the invention might use different acquisition strategies, like 2D, 3D slab-selective, 3D non-selective, and different sequence types for the readout blocks of the acquisition, like FLASH, bSSFP, etc..

Preferentially, different metrics for dictionary fitting than a cross-product between absolute quantities can be used, like calculating a minimum root mean square error or an absolute difference.

Finally, while the method described a preferred embodiment based on a dictionary fitting procedure, other techniques for matching experimental data with simulated data, e.g. with a physics-based model, can be used to estimate the relaxation parameters (e.g., the physics-based model can be embedded in the reconstruction of the input images to output directly quantitative maps).

Claim 1:
Quantitative Magnetic Resonance Imaging, hereafter qMRI, method for mapping one or several qMRI parameters of a biological object (<NUM>) with an MRI system (<NUM>), the method comprising the following steps:
- performing (<NUM>), by the MRI system (<NUM>), N scans C_1,...,C_N, wherein each scan C_j, with j = <NUM>,...,N, comprises:
- performing (<NUM>) one or several magnetization preparation radio frequency (hereafter "RF") pulse series, each followed by M_j readout blocks, wherein two successive magnetization preparation RF pulse series are separated by a repetition time interval TR_j (<NUM>), wherein each magnetization preparation RF pulse series is a T2-prepared inversion pulse series (<NUM>) comprising multiple pulses (<NUM>) and characterized by an echo time, i.e. inter-pulse duration, TEp_j, wherein said inter-pulse duration is varied by the MRI system in order to obtain different T2 weightings, the magnetization preparation RF pulse series being configured for inverting longitudinal magnetization while encoding T2 contrast in subsequent T1 recovery;
- an acquisition (<NUM>), by the MRI system (<NUM>) and during each readout block, of an MRI recovery signal generated by at least a part of said biological object (<NUM>), wherein for each readout block R_i,j, an MRI signal S_i,j is acquired by the MRI system at a different inversion time TI_i,j, with i=<NUM>,...,M_j, and M_j ≥ <NUM>;
- reconstructing (<NUM>), for and from each MRI signal S_i,j, an image I_i,j of said part;
- creating (<NUM>) a voxel-wise signal (<NUM>) by concatenating intensity values (<NUM>) obtained for a same voxel for the reconstructed images;
- fitting (<NUM>) a physical model to the concatenated intensity values (<NUM>) to obtain at least one qMRI map of one of said qMRI parameters.