Magnetic resonance imaging with multiple contrasts
The DESS imaging sequence allows for the derivation of multiple biomarkers from a single MRI scan, enhancing tumor detection sensitivity and specificity without the need for contrast agents, addressing the inefficiencies of current MRI techniques.
Patent Information
- Application Number
- PCT/EP2024/086717
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2023-12-21
- Filing Date
- 2024-12-17
- Publication Date
- 2025-06-26
AI Technical Summary
Current magnetic resonance imaging (MRI) techniques require multiple scans to derive various biomarkers for tumor detection and diagnosis, which can be time-consuming and may involve the use of contrast agents.
A method utilizing a double-echo steady-state (DESS) imaging sequence that samples multiple coherence pathways, allowing for the derivation of quantitative susceptibility mapping, quantitative conductivity mapping, T2 weighted information, and diffusion weighted information from a single scan.
Enables the acquisition of multiple tissue contrasts efficiently from a single MRI scan, improving tumor detection sensitivity and specificity by providing comprehensive biomarker information without the need for contrast agents.
Smart Images

Figure EP2024086717_26062025_PF_FP_ABST
Abstract
Description
[0001]2023PF00850 1 MAGNETIC RESONANCE IMAGING WITH MULTIPLE CONTRASTS FIELD OF THE INVENTION The invention relates to the field of magnetic resonance imaging. It concerns methods and systems for magnetic resonance imaging of an object. BACKGROUND OF THE INVENTION Image-forming magnetic resonance methods that utilize the interaction betweenmagnetic fields and nuclear spins in order to form two-dimensional or three-dimensional images are widely used nowadays, notably in the field of medical diagnostics, because for soft tissue imaging they are superior to other imaging methods in many respects, e.g., do not require ionizing radiation and are usually not invasive. Quantitative magnetic resonance imaging is one of the imaging techniques that potentially could be used for non-invasive diagnosis, in particular Electrical PropertiesTomography (EPT). An extensive review of EPT is to be found in Leijsen R., et al.,“Electrical Properties Tomography: A Methodological Review”, Diagnostics 2021, 11, 176, https: / / doi.org / 10.3390 / diagnostics11020176, which is hereby incorporated by reference in its entirety. WO2020 / 254571 A1 discloses a method of Magnetic Resonance Imaging (MRI)of an object placed in an examination volume of a Magnetic Resonance (MR) device,wherein the method comprises the steps of: subjecting the object to a multi-echo steady-state imaging sequence comprising radiofrequency (RF) pulses and switched magnetic field gradients, wherein two or more echo signals are generated in each interval between successive RF pulses, wherein the imaging sequence comprises diffusion weighting magnetic field gradients; acquiring the echo signals in a number of repetitions of the imaging sequence; deriving at least one magnitude image and at least one phase map from the acquired echo signals, which phase map represents the spatial RF field distribution induced by the RF pulses in the object; and reconstructing an electric conductivity map from the MR image and from the phase map, wherein boundaries between normal and suspicious tissues are derivedon the basis of diffusion weighting in the at least one magnitude image for reconstructing theelectric conductivity map from the phase map. The method enables MR signal acquisition in 2023PF00850 2 a single scan by providing the information necessary for EPT, namely a phase map as well as tissue boundaries for tumor delineation, thereby the MR image acquisition technique having a tumor detection sensitivity comparable to dynamic contrast enhanced MR imaging (DCE).MR device and computer program to be run on an MR device are also disclosed, whichcomputer program comprises instructions for carrying out the MR imaging method listedhereinbefore. WO2020 / 254571 A1 is hereby incorporated by reference in its entirety. M-L. Wu et al: "Midbrain nuclei visualization improved by susceptibility-enhanced 3D multi-echo SSFP for deep brain stimulation guidance", Proceedings of the International Society for Magnetic Resonance in Medicine, vol.18, 17April 2010, page 701, and Wu Ming-Long et al.: "Efficient imaging of midbrain nuclei usinginverse double-echo steady-state acquisition)", Medical Physics, vol.42, no.7, 26 June 2015, pages 4367-4374, describe the connection of Double-Echo Steady-State (DESS) and Susceptibility-Weighted-Imaging (SWI).Jong-Min Kim et al.: "Monitoring and Guidance on High-Intensity Focused Ultrasound Treatment by Multiple Fast Field Echo at 3.0 T MRI: Ex- Vivo Studies with Multiparametric Mapping", Proceedings of the International Society for Magnetic Resonance in Medicine, vol.26, 1485, 1 June 2018, and Han-Jae Chung et al.: "Electro-Magnetic Property Mapping Using Kalman Filtering with a Single Acquisition at 3.0 T and 7.0 T MRI", Proceedings of the International Society for Magnetic Resonance in Medicine, vol.26, 5081, 1 June 2018, describe the connection of DESS and Quantitative- Susceptibility-Mapping (QSM). Improving MR imaging methods for detection, delineation and specification oftumor is a continuous effort in the continuum of care. SUMMARY OF THE INVENTION It is an object of the invention to provide methods and systems for MR signalacquisition in a single scan from which additional biomarkers can be derived, contributing to improved sensitivity and specificity in diagnosis of tumors, being that prior or post treatment. According to an aspect of the invention a method is disclosed, comprising: obtaining magnetic resonance imaging data by subjecting an object, preferably aportion of the body of a subject, to a double-echo steady-state imaging sequence that samplesmultiple coherence pathways, wherein two or more echo signals are generated in each interval between successive RF pulses; deriving quantitative susceptibility mapping from the magnetic resonanceimaging data; 2023PF00850 3 outputting to a display an image based on the quantitative susceptibility mapping.In an embodiment, the method may further comprise: deriving quantitativeconductivity mapping from the magnetic resonance imaging data; outputting to the display animage based on the quantitative conductivity mapping.In an embodiment, the method may further comprise: deriving T2 weightedinformation from the magnetic resonance imaging data; outputting to the display an imagebased on the T2 weighted information. In an embodiment, the double-echo steady-state imaging sequence comprisesdiffusion sensitizing gradients, and the method may further comprise: deriving diffusionweighted information from the magnetic resonance imaging data; outputting to the display animage based on the diffusion weighted information. The invention provides various image contrasts that can be derived time-efficientlyfrom a single scan, such as for example quantitative susceptibility mapping with acombination of any of the T2 weighted image, diffusion weighted image and quantitativeconductivity mapping, all representing various biomarkers of which combination can lead todistinguishing different types of diseases and / or evolution of a specific type of disease (e.g.,cancer). In oncology, for example, well co-localized imaging information is highly desirable,such as T2 relaxation supporting localization of tumor tissue, diffusion being indicative oftumor microstructure / cellularity, susceptibility being indicative of tumor hemorrhage ormicro-hemorrhage and electrical properties such as conductivity being indicative of tumormalignancy via cell membrane effects and sodium content. It is to be noted that DESS is not equivalent to multiple-Fast-Field-Echo (mFFE),and that Susceptibility-Weighted-Imaging (SWI) is not equivalent to Quantitative-Susceptibility-Mapping (QSM). In any of the embodiments of the method, tissue boundaries may be derivedbased on signal magnitude of one of the multiple echoes. In a preferred embodiment the firstecho is used for tissue boundary detection, because the echo at TE+typically shows a higherSignal to Noise Ratio (SNR) than the other echo(s).In an embodiment of the method, deriving tissue boundaries involves asegmentation of a magnitude image. In alternative embodiment the boundaries betweennormal and suspicious tissues may be derived based on diffusion weighting in the at least onemagnitude image. In some of the embodiments the segmentation of magnitude image may be basedon deep learning or machine learning. 2023PF00850 4 In some embodiments deriving tissue boundaries may be a prerequisite ofderiving susceptibility and / or conductivity information. In some embodiments deriving quantitative susceptibility mapping is preceded byproviding segmentation of the anatomy of the imaged portion of the body into one or more anatomical regions. The portion of the body for segmentation of the anatomy may be selectable by a user through a user interface, e.g., touch screen, mouse, through a predefined menu, tab. In some of the embodiments outputting the image may comprise replacing eachof the segmented one or more anatomical regions with corresponding quantitativesusceptibility mapping. In some of the embodiments this holds also for quantitativeconductivity mapping. In some of the embodiments outputting the image comprises overlayingquantitative susceptibility mapping on the respective one or more anatomical regions on ananatomic image, wherein the anatomic image is preferably the magnetic resonance image used for providing the image segmentation. According to a further aspect of the invention, a system for magnetic resonanceimaging is disclosed, comprising a processor configured to perform any of the methodembodiments according to the invention. In some embodiments the system may comprise: a magnetic resonance imaging system for providing the magnetic resonance imaging data and a screen display configured to display the one or more images according to the invention. In a further aspect of the invention a computer program comprising machineexecutable instructions is disclosed, wherein execution of the machine executableinstructions causes a computational system to perform any of the method embodiments according to the invention. Features described above with respect to method embodiments are applicable and are contemplated also for corresponding system embodiments, with similar benefits. This Summary is provided to introduce a selection of concepts in a simplifiedform that are further described below in the Detailed Description. This Summary is not intended to identify key features or essential features of the claimed subject matter, nor is it intended to limit the scope of the claimed subject matter. A more extensive presentation of features, details, utilities, and advantages of the system, as defined in the claims, is provided in the following written description of various embodiments of the disclosure and illustrated in the accompanying drawings. 2023PF00850 5 BRIEF DESCRIPTION OF THE DRAWINGS 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: Fig. 1 shows a system for carrying out the method according to the invention;Fig. 2 illustrates a method of magnetic resonance imaging according to theinvention; Fig.3 shows an exemplary computation flowchart according to the invention; Fig.4 illustrates exemplarily the four different contrast images obtainable from a single scan, according to the invention; Fig.5 shows quantitative susceptibility mapping and quantitative conductivitymapping images of the same phantom used for the example in Fig. 4, but for which the datawas acquired with respective conventional scanning sequences; Fig.6 double-echo steady state sequence using two single-echoes at the beginning and end of TR; Fig.7 double-echo steady state sequence using two echo trains. DETAILED DESCRIPTION OF THE EMBODIMENTS For the purposes of promoting and understanding the principles of the present disclosure, reference will now be made to the embodiments illustrated in the drawings, and specific language will be used to describe the same. It is nevertheless understood that no limitation to the scope of the disclosure is intended. Any alterations and further modifications to the described devices, systems, and methods, and any further application of the principles of the present disclosure are fully contemplated and included within the present disclosure as would normally occur to one skilled in the art to which the disclosure relates. In particular, it is fully contemplated that the features, components, and / or steps described with respect to one embodiment may be combined with the features, components, and / or steps described with respect to other embodiments of the present disclosure. For the sake of brevity, however, thenumerous iterations of these combinations will not be described separately. Features describedin relation to a system, may be implemented in a computer implemented method and / or in a computer program product, in a corresponding manner. With reference to Fig. 1, an MR system 1 is shown. The system comprisessuperconducting or resistive main magnet coils 2, 2’ such that a substantially uniform, temporally constant main magnetic field is created along a z-axis through an examination 2023PF00850 6 volume. 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. 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 transmitter 7 transmits RF pulses or pulse packets, via a send / receive switch 8, to a whole-body volume RF coil 9 to transmit RF pulses into the examination volume. A typical MR imaging sequence is composed of a packet of RF pulse segments ofshort duration, which taken together with each other and any applied magnetic field gradientsachieve 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 arealso picked up by the whole-body volume RF coil 9 and / or by the array RF coils 11, 12, 13.For generation of MR images of limited regions of the body 10, 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. The resultant MR signals are picked up by the whole-body volume RF coil 9and / or by the array RF coils 11, 12, 13 and are demodulated by a receiver 14, preferablyincluding a preamplifier (not shown). The receiver 14 is connected to the RF coils 9, 11, 12 and 13 via send / receive switch 8. A host computer 15 controls the gradient pulse amplifier 3 and the transmitter 7 to generate any of a plurality of MR imaging sequences, such as Double-Echo Steady-State(DESS) imaging sequence, Diffusion Weighted Double-Echo Steady-State (DW-DESS)imaging sequence or 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. The dataacquisition system 16 may be a separate computer that is specialized in acquisition of rawimage data, such as implemented in modern MR systems. The acquired MR data may bestored in a memory, which is intended to represent any combination of memory or storage devicewhich is accessible to a computational system configured to control the MR acquisition and / or 2023PF00850 7 reconstruction. The memory may include volatile and non-volatile memory storage means and components. The memory in some embodiments may be based on or may rely on cloud-based datastored in logical pools across disparate, commodity storage servers located on premises or in a datacenter managed by a third-party cloud provider. Eventually, the digital raw image data is reconstructed into an imagerepresentation by a reconstruction processor 17, which applies a Fourier transform or otherappropriate reconstruction algorithms, such as SENSE, SMASH, 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 orscreen display 18, which provides a man-readable display of the resultant MR image.With continuing reference to Fig.1 and with further reference to Fig.2 anembodiment of the method according to the invention is explained in the following.A valuable advantage of MRI is given by the multitude of image contrasts available, reflecting different biomarkers for diagnosis. Examples of biomarkers may be obtained by diffusion weighted imaging (DWI), by Quantitative Susceptibility Mapping (QSM) and / or by Electrical Properties Tomography (EPT), providing different contrasts, which are usually obtained by employing separate MR sequences. According to an aspect of the invention, a method 100 of magnetic resonanceimaging is provided, illustrated in Fig.2. In step 102 magnetic resonance imaging data isprovided by an MR system 1 through subjecting the body 10 or a portion of the body to asteady-state imaging sequence that samples multiple coherence pathways (MESS), which forexample may be a DESS sequence, Triple-Echo Steady-State (TESS) sequence, wherein twoor more echo signals are generated in each interval between successive RF pulses. In general,steady-state imaging sequences are based on a gradient echo imaging sequence with a short repetition time. Steady-state sequences include transverse coherences from overlapping multi-order spin echoes and stimulated echoes. This is usually accomplished by refocusingthe phase-encoding gradient in each repetition interval, in order to keep the phase integral (orgradient moment) constant. Fully balanced steady state imaging sequences achieve a phase ofzero by refocusing all imaging gradients. Both the phase map and the tissue contrast can bederived from a single scan by using one of the MESS sequences for acquiring the magneticresonance imaging data. In step 104 quantitative susceptibility mapping is derived from the magnetic 2023PF00850 8resonance imaging data by using a processor or a computing system. The processor may beintegrated in the system 1 either separate or within any of the processing sub-systems 15 and17. Quantitative susceptibility and conductivity mapping may be obtained by usingthe phase behavior of the magnetic resonance imaging data acquired with the MESSsequence, e.g., DESS sequence. The phase behavior depends on the position of the spoilergradient required for this sequence. For instance, the phase maps ^^+and ^^–of the two echoes of a DESS sequence with a spoiler gradient located symmetrically between the two echoes yields: ^^= 0.5 (^^++ ^^–) [1] ^B0 = 0.5 ^^-1 (^^+ – ^^–) / TE [2]wherein TE is the echo time, ^^is the phase originating from B1, and ^B0is the B0inhomogeneity (or inhomogeneity field map) induced by the magnetic susceptibility and other sources. Equations [1] and [2] can be used as input to calculate quantitativesusceptibility ^ and conductivity ^, respectively^^In a second example, the spoiler gradient of a DESS sequence is located after thesecond echo. In this case, the phase maps of two different repetition times TRa and TRb are required: ^^^ ^= 0.5(^^ + ^^) − 0.5^^ ^^^ ^ ^^^^^^^^ (^^^ − ^^) [3] Equations [3] and [4] can again be used as input to calculate quantitative susceptibility ^ andconductivity ^^ Susceptibility ^ is related to ^B0 via the unit dipole field kernel d as described bythe equation: ^ ^B0 = B0 d ^ ^ [5]which can be solved for the unknown ^ by using the computational technique described in 2023PF00850 9 Wang Y, Liu T, “Quantitative Susceptibility Mapping (QSM): Decoding MRI Data for a Tissue Magnetic Biomarker” Magnetic Resonance in Medicine 73:82–101(2015), which is hereby incorporated by reference in its entirety. Conductivity ^ is related to ^1 as described by the (truncated) Helmholtzequation: ^= (^^1) / (2^^0) [6]wherein ^ is the Laplace operator, ^ is the Larmor frequency of the MR system used, and ^0is the vacuum permeability. The electrical properties such as conductivity and permittivity (incase that not only B1phase, but also B1magnitude is provided) can be derived by using the computational technique disclosed in Katscher U, van den Berg CAT, “Electric properties tomography: Biochemical, physical and technical background, evaluation and clinicalapplications”, NMR Biomed. 2017; e3729; https: / / doi.org / 10.1002 / nbm.3729, which ishereby incorporated by reference in its entirety. Since both, the phase map and the tissue contrast can be derived from a singlescan by using one of the MESS sequences for acquiring the magnetic resonance imagingdata, besides the conductivity and susceptibility it is possible to derive the boundaries between different tissue types. Therefore, no error-prone registering of the image data of two or more independent scans is necessary for obtaining the different contrasts indicative forproperties of anatomical tissue. Potential patient movement between the separate sequencesrequires registration of the different images, which is critical, particularly in case wherediagnosis of joints of patent are involved. In oncology, for example, well co-localizedimaging information is highly desirable. An additional advantage of deriving multiple tissuecontrasts from single scan is that potentially no contrast agent needs to be administered to thepatient for obtaining the various data. The calculation of both, ^ and ^, may benefit from a-priori knowledge of tissueboundaries conform the techniques used in Wang Y, Liu T, “Quantitative Susceptibility Mapping (QSM): Decoding MRI Data for a Tissue Magnetic Biomarker” Magnetic Resonance in Medicine 73:82–101(2015) and / or Katscher U, van den Berg CAT, “Electric properties tomography: Biochemical, physical and technical background, evaluation and clinical applications”, NMR Biomed.2017; e3729, hereby incorporated by reference in theirentirety, which tissue boundaries can be extracted from the signal magnitude of one of theechoes. As the echo at TE+typically shows a higher SNR than the other echo(s), it is 2023PF00850 10 recommended to use this echo for tissue boundary extraction. Tissue boundary determination can be improved by taking multiple magnitude images into account. For example, an edge detection algorithm, like the known Sobel or Canny algorithm, can be used and the results can be combined by straight-forward superposition or by locally weighted averaging. In a further preferred embodiment, the step of deriving tissue boundaries involves a segmentation of the magnitude image (or multiple magnitude images). A knownsegmentation technique may be employed, such as, e.g. deep learning (DL) based imagesegmentation, preferably using (regional) convolutional neuronal networks (CNN). Segmentation is the process of partitioning the magnitude image(s) into multiple regions that share similar attributes, thus yielding the boundaries between different tissue types (healthy tissue vs. suspicious / cancerous tissue). Image segmentation has recently become the biggest target for DL approaches in medical imaging. MR image segmentation using DL, typically CNNs, has been proposed in almost the whole field of applications, whereof breast and brain tumor segmentation are only examples. Diffusion sensitivity may be induced in the multi-echo steady-state imagingsequence by adding diffusion weighting magnetic field gradients. By using a strong diffusion gradient moment in the steady-state sequence, the resulting diffusion weighting highlights tumors with positive contrast as areas of restricted diffusion and thus enables to distinguish tumor and ductal tissue (see Granlund K.L. et al., “High-resolution, three-dimensional diffusion-weighted breast imaging using DESS”, Magn. Reson. Imaging., 2014, 32, 330–341, hereby incorporated by reference in its entirety). DESS generates two echo signals between successive RF pulses, namely a Free Induction Decay (FID) signal and an echo signal from the steady-state free precession of the magnetization individually in each repetition. Phase encoding magnetic field gradients are balanced to maintain the steady-state of transverse magnetization. The collection of two signals (FID and echo signals) provides a means to correct for relaxation weighting and further provides the diffusion weighting and, thus, excellent tumor contrast in the magnitude image such that lesions can be detected and boundaries between normal and suspicious tissues can be derived, which may be in anoptional embodiment a prerequisite for phase-based conductivity imaging and / orsusceptibility imaging. The phase map is suitable for EPT if it only relates to B1, and it is not influenced by inhomogeneity of the main magnetic field B0. Conventionally, any unwanted influence of B0 inhomogeneity is avoided by using spin-echo based imaging sequences. The 2023PF00850 11 invention exploits that unwanted B0 inhomogeneity influences on the phase map are negligible in steady-state acquisitions, because the phase remains almost unchanged for off- resonances within the pass band (frequency range corresponding to 1 / TR). In a DiffusionWeighted DESS (DW-DESS) acquisition, e.g., the B1-related phase map can directly bederived for each position in a reconstructed complex MR image from the real and imaginaryparts of the respective image value. The same holds in principle for other multi-echo steady-state imaging sequences, like, e.g., TESS (see Kraff O. et al., “7 Tesla quantitative hip MRI: a comparison between TESS and CPMG for T2 mapping”, Magnetic Resonance Materials in Physics, Biology and Medicine, 2016, 29(3), 503-512, which is hereby incorporated by reference in its entirety). In one embodiment, two or more complex MR images are reconstructed suchthat each of the complex MR images is associated with one echo time value, i.e. one subset of echoes of the multi-echo steady-state imaging sequence. In the case of a DESS imaging sequence, two MR images are obtained from the two echoes generated in each interval between two successive RF pulses (or three MR images in the case of a TESS imaging sequence). A magnitude image and a phase map can then be derived from each complex MR image. In all cases, the MR images associated with the different echoes yield in principle the same phase map, but, of course, the magnitude images differ in their contrast. This can be utilized for reconstructing the electric conductivity map. Preferably, independent conductivity maps are calculated from the different sets of magnitude images and phase maps, and the conductivity maps are then combined into a final conductivity map, either by simple superposition (to obtain an average conductivity map as the final result) or by weighted averaging taking the signal-to-noise-ratio (SNR) into account such that the conductivity is taken at each image position with the largest SNR at the respective position. As disclosed in various embodiments according to the invention, the MESS sequence, e.g., DESS sequence, can either comprise diffusion weighting gradients in the sequence or not, depending on the number of biomarkers to be assessed by the medicalpersonnel. Accordingly, referring to Fig. 2, in step 104 conductivity can be derived from themagnetic resonance imaging data besides susceptibility information as illustrated with the exemplary computation flowchart 200 in Fig.3. The magnetic resonance data is provided bye.g., a patient scan 202 using a DESS imaging sequence, from which two complex images204 and 206 can be derived based on the two different echoes. From the phase maps of theseechoes, the B1-phase ^1208 as well as the field map ^B0210 can be obtained, essentiallybased on adding or subtracting the two phase maps, respectively. Quantitative conductivity 2023PF00850 12212 and / or susceptibility 214 mapping are then derived based on ^1 and ^B0. In optionalembodiments, as already disclosed hereinbefore, deriving either one of quantitativesusceptibility and conductivity may benefit from taking tissue boundaries into account, whichinformation can be extracted from S+and is illustrated by the dashed line in Fig.3. Accordingly, for studies where only the T2 weighting, susceptibility and conductivity is regarded important, by skipping the diffusion weighting gradients in thesequence, two advantages can be obtained: repetition time (TR) gets shorter, and so does thetotal acquisition time, whereas also the SNR of the second echo increases, which is particularly valuable for the arithmetic of the phase maps required to derive quantitativesusceptibility and conductivity mapping as described above. In some embodiments,optionally, tissue boundary can be delimited based on signal magnitude S+, as illustrated inFig.3. In clinical cases with increased complexity, all potential biomarkers that can beobtained from a single scan may be particularly valuable for assessment of anomalies. Inoncology, for example, well co-localized imaging information is highly desirable, such as T2relaxation supporting localization of tumor tissue, diffusion being indicative of tumormicrostructure / cellularity, susceptibility being indicative of tumor hemorrhage or micro-hemorrhage, and electrical properties such as conductivity being indicative of tumormalignancy via cell membrane effects and sodium content. In some embodiments, optionally,tissue boundary can be delimited based on signal magnitude S+, whereas in otherembodiments, the boundaries between normal and suspicious tissues may be derived basedon diffusion weighting in the at least one magnitude image.In order to suppress signal contributions from fat in applications like breastcancer diagnosis, the steady-state sequence is preferably performed with additional fatsuppression, e.g., by employing spectrally selective RF pulses (water only excitation).Experiments performed on a phantom comprising an inner compartment with acomposition of 1.5 mg zinc + 1 g sodium / liter H2O and an outer compartment with acomposition of 0.1 g sodium / liter H2O illustrate the feasibility of the method according tothe invention. A DESS sequence was used for acquiring the magnetic resonance imagingdata, with the following scan parameters: acquisition voxel of 2x2x4 mm³; field of view of180x180x120 mm³; number of signal averages of 4; scan time of about 4 min; TR / TE of26 / 4.1 ms; flip angle of 25°; coronal slices. Fig. 4 illustrates the results, wherein (A) is theT2-weighted image, (B) is the diffusion weighted image, (C) is the quantitative susceptibility mapping image and (D) is the quantitative conductivity mapping image. The same phantom 2023PF00850 13 has been imaged with other acquisition sequences for comparison of the various imagesobtained by using the DESS acquisition sequence. Fig. 5 illustrates quantitative susceptibilitymapping image in (E) for an acquisition according to a multi-echo Fast Field Echo (mFFE)sequence, for which the duration of the data acquisition was about three minutes. Goodcorrelation of the susceptibility images can be observed by comparison of Fig. 4 (C) with Fig.5 (E). Similarly, a comparison of the conductivity images in Fig. 4 (D) and Fig. 5 (F) showsgood correlation between the quantitative conductivity mapping image derived from the acquisition according to the DESS sequence and the conductivity image derived from anacquisition according to balanced Fast Field Echo (bFFE) with an acquisition duration ofabout two minutes. Accordingly, the invention provides various image contrasts that can be derivedtime-efficiently from a single scan, such as for example quantitative susceptibility mappingwith a combination of any of the T2 weighted image, diffusion weighted image andquantitative conductivity mapping, all representing various biomarkers of which combinationcan lead to distinguishing different types of diseases and / or evolution of a specific type ofdisease (e.g., cancer). Referring to Fig. 2, in step 106 of the method one or multiple images may be outputto a display based on the susceptibility information. In optional embodiment the quantitativesusceptibility mapping results may be overlayed on any other magnetic resonance imagegenerated from the magnetic resonance imaging data, for example the anatomic image based on T2 weighted image. Colorbars may be output corresponding to the scales of values of properties presented in the generated image or multiple images. The method of the invention described thus far can be carried out by means of anMR system or device, e.g., illustrated in Fig. 1, including at least one main magnet coil forgenerating a uniform static 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 an object positioned in the examination volume, a control unit for controlling the temporal succession of RF pulses and switched magnetic field gradients, and a reconstruction unit. The method of the invention can be implemented, for example, by a corresponding programming. 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. 2023PF00850 14 So far it has been discussed the method to obtain quantitative susceptibilityand / or quantitative conductivity mapping for a portion of the body subjected to DESS imaging sequence, which is based on acquiring a single-echo at the beginning of the TR and another single-echo at the end of the TR. Additional advantages regarding imaging speed and / or SNR can be conferred to the technique by further modification of the conventional DESS imaging sequence, illustrated in Fig.6, in particular by acquiring not only the two single-echoes, but two echo trains of predetermined lengths, such as presented in Fig.7,wherein the two echoes sp and sm (indices p and m for “plus” and “minus”) are replaced bytwo echo trains spa and smb with length a ^ A and b ^ B.This concept can be utilized in various embodiments, from which only several nonlimiting examples are listed. In exemplary embodiments the train of read-out gradients can be realized with or without interleaved blips (gradient pulses) in phase-encoding direction. In one of thealternatives with blips, different k-space profiles are acquired within the echo trains, yieldinga reduction of total acquisition time Tacq. In a different alternative without blips, the same k- space profile is acquired multiple times, which increases the SNR efficiency of the sequence (i.e. SNR / ^Tacq). In a further embodiment without interleaved blips, several options exist for additional contrast generation: (a) the magnitude of the different echoes reveal T2* decay and allow aquantitative determination of T2* by fitting exponentials voxel by voxel; (b) the phase map ^n of echo n at echo time TEn is given by ^n = ^1 + ^^TEn ^B0with the B1-related phase ^1, ^ the gyromagnetic ratio, and ^B0 the spatial B0inhomogeneity map. Voxel by voxel, ^B0 and ^1 can be fitted as slope or intercept over thedifferent TEn , and can be used as input to calculate quantitative magnetic susceptibility ^ andquantitative electric conductivity ^^ In contrast to conventional single-echoes DESS, whereinboth echoes have to be taken into account to determine ^B0and ^1, the double-echo steady- state with multi-echo trains (DESS-MET) enables determination of ^B0 and ^1 from the first echo train only. This is advantageous as the second echo or the second echo train typically suffers from lower SNR; (c) using the combination of magnitude and phase of the different echoes from any of the alternative embodiments (a) and (b) from above, chemical shift encoding can be performed, for example to obtain water and fat signals via a multi-point Dixon technique. 2023PF00850 15 In further alternative embodiments for both possibilities, whether the read-out gradients are realized with or without interleaved blips in phase-encoding direction, a diffusion weighting gradient can be inserted between the echo trains of the sequence, such as illustrated in Fig.7, denoted with Ds1, Ds2. This diffusion weighting gradient might have a unipolar or bipolar shape, for instance. The diffusion weighted image is obtained from the ratio sm / sp. Due to the proposed introduction of echo trains, this diffusion weighted imaging has a higher SNR efficiency when used with interleaved blips and a shorter acquisition time Tacq when used with interleaved blips, as detailed above. DESS is prone to banding artefacts. These banding artefacts can be removed via phase cycling or via a spoiler gradient. Any unbalanced gradient moment in the sequence can act as spoiler. For instance, the mentioned unipolar diffusion gradient is acting as a spoiler. In case of the proposed echo trains, the spoiler gradient may be obtained, for example by trainlengths differing by a unity, i.e. B = A ± 1.Although various embodiments associated to multi-echo trains have been detailed for double-echo steady-state imaging sequence for illustrative purpose, herewith it is contemplated to apply the multi-echo trains also to Triple-Echo Steady-State (TESS) and corresponding higher-order sequences. As will be appreciated by one skilled in the art, aspects of the present inventionmay be embodied as a system, method or computer program product. Accordingly, aspects ofthe 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 or computational system 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 computational system of the computing 2023PF00850 16 device. Examples of computer-readable storage media include, but are not limited to: 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 computational system. 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, 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 computational system. ‘Computer storage’ or ‘storage’ is a further example of a computer-readable storage medium. Computer storage is any non-volatile computer-readable storage medium. In some embodiments computer storage may also be computer memory or vice versa. A ‘computational system’ 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 computational system comprising the example of “a computational system” should be interpreted as possibly containing more than one computational system or processing core. The computational system may for instance be a multi-core processor. A computational system may also refer to a collection of computational systems within a single computer system or distributed amongst multiple computer systems. The term computational system should also be interpreted to possibly refer to a collection or network of computing devices each comprising a processor or computational systems. The machine executable code or instructions may be executed by multiple computational systems or processors that may be within the same computing device or which may even be distributed across multiple computing devices. 2023PF00850 17 Machine executable instructions or computer executable code may comprise instructions or a program which causes a processor or other computational system 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 moreprogramming 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 machineexecutable instructions. In some instances, the computer executable code may be in the formof 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. In other instances, the machine executable instructions or computer executable code may be in the form of programming for programmable logic gate arrays. The computer executable code may execute entirely on the user's computer, partly on the user's computer, as a stand-alone software package, partly on the user'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's computer through any type of network, including a local area network (LAN) or a wide area network (WAN), or theconnection may be made to an external computer (for example, through the Internet using anInternet 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 aportion of the blocks of the flowchart, illustrations, and / or block diagrams, can beimplemented 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 computational system of a general-purpose computer, special purpose computer, or other programmable data processingapparatus to produce a machine, such that the instructions, which execute via the computational system 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 machine executable instructions or computer program instructions may also be stored in a computer readable medium that can direct a computer, other 2023PF00850 18 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 machine executable instructions or 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 operatorand / 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 to indicate the effects of the operator'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 computational system of a computer system to interact with and / or control an external computing device and / or apparatus. A hardware interface may allow a computational system to send control signals or instructions to an external computing device and / or apparatus. A hardware interface may also enable a computational system 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. 2023PF00850 19 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. All directional references e.g., upper, lower, inner, outer, upward, downward, left, right, lateral, front, back, top, bottom, above, below, vertical, horizontal, clockwise, counterclockwise, proximal, and distal are only used for identification purposes to aid the reader’s understanding of the claimed subject matter, and do not create limitations, particularly as to the position, orientation, or use of the reinforced multi-filar conductor bundle. Connection references, e.g., attached, coupled, connected, and joined are to be construed broadly and may include intermediate members between a collection of elements and relative movement between elements unless otherwise indicated. As such, connectionreferences do not necessarily imply that two elements are directly connected and in fixedrelation to each other. The term “or” shall be interpreted to mean “and / or” rather than “exclusive or.” The word "comprising” does not exclude other elements or steps, and the indefinite article “a” or “an” does not exclude a plurality. Unless otherwise noted in the claims, stated values shall be interpreted as illustrative only and shall not be taken to be limiting. Although various embodiments of the claimed subject matter have been described above with a certain degree of particularity, or with reference to one or more individual embodiments, those skilled in the art could make numerous alterations to the disclosed embodiments without departing from the spirit or scope of the claimed subject matter. Still other embodiments are contemplated. It is intended that all matter contained inthe above description and shown in the accompanying drawings shall be interpreted as illustrative only of particular embodiments and not limiting. Changes in detail or structure may be made without departing from the basic elements of the subject matter as defined in the following claims.
Claims
2023PF00850 20 CLAIMS1. A method (100) of magnetic resonance imaging, comprising:receiving magnetic resonance imaging data (102) comprising information of atleast a portion of a body (10) subjected to a double-echo steady-state imaging sequence;deriving quantitative susceptibility mapping (104, 214) from the magnetic resonance imaging data; outputting to a display an image (C) based on the quantitative susceptibility mapping.
2. The method of claim 1, further comprising:deriving quantitative conductivity mapping (212) from the magnetic resonance imaging data; outputting to the display an image (D) based on the quantitative conductivitymapping.
3. The method of claim 1 or 2, wherein the double-echo steady-state imagingsequence is adapted for acquiring two echo trains of predetermined lengths.
4. The method of any of the preceding claims, further comprising:deriving T2 weighted information from the magnetic resonance imaging data; outputting to the display an image (A) based on the T2 weighted information.
5. The method of any of the preceding claims, wherein the double-echo steady-stateimaging sequence comprises diffusion sensitizing gradients, and wherein the method further comprises: deriving diffusion weighted information from the magnetic resonance imaging data; outputting to the display an image (B) based on the diffusion weightedinformation.2023PF00850 216. The method of any of the preceding claims, wherein tissue boundaries are derivedbased on signal magnitude of one of the multiple echoes.
7. The method of claim 6, wherein the first echo is used for tissue boundarydetection.
8. The method of claim 6 or 7, wherein deriving tissue boundaries involves asegmentation of a magnitude image.
9. The method of claim 8, wherein the segmentation of the magnitude image isbased on deep learning.
10. The method of any of the claims 6 to 9, wherein deriving tissue boundaries is aprerequisite of deriving quantitative susceptibility mapping.
11. The method of any of the preceding claims, wherein deriving quantitativesusceptibility mapping is preceded by providing anatomical segmentation of the imaged portion of the body into one or more anatomical regions.
12. The method of claim 11, wherein outputting the image comprises replacing eachof the segmented one or more anatomical regions with corresponding quantitative susceptibility mapping.
13. The method of claim 11, wherein outputting the image comprises overlayingquantitative susceptibility mapping on the respective one or more anatomical regions on an anatomic image, wherein the anatomic image is preferably the magnetic resonance image used for providing the image segmentation.
14. A system (1) for magnetic resonance imaging, comprising:- a processor (17) configured to perform a method according to any of the claims 1to 13.
15. A computer program comprising machine executable instructions, whereinexecution of the machine executable instructions causes a computational system to perform a2023PF00850 22 method according to any of the claims 1 to 13.
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