The present invention concerns a method and an apparatus for identifying at least one material comprised in a voxel according to the independent claims. This method can be used for medical MRI or material analysis purposes.
Magnetic resonance (MR) has become a very powerful tool for biomedical diagnosis and material testing. This can be attributed to the fact, that each material (e.g. biological tissue type or synthetic material) has unique relaxation time constants T1 and T2, also known as longitudinal and transverse relaxation times respectively. When there are multiple materials in a voxel, T1 and T2 relaxation time distributions (i.e. spectra) can be obtained independently with two measurements, e.g. using an inversion-recovery (IR) FLASH sequence for generating a T1 spectrum or a Carr-Purcell-Meiboom-Gill (CPMG) sequence (or generating a T2 spectrum.
However, a correlation between the T1 and T2 values is not possible in that way. In other words, when there are multiple peaks in the spectra it is not possible to determine which T2-value correlates to which T1-value or conversely, which T1-value correlates to which T2-value. Therefore, T1-/T2-correlation measurements are highly preferred for a better identification of material or tissue types. In principle, this is possible with the IR-CPMG method but requires significantly longer scan times. For example, typically a plurality of measurements (e.g. N=) with different system setting (e.g. inversion times TI) need to be performed. Each individual measurement takes several seconds and therefore, the overall scan time is on the order of several minutes depending on the desired accuracy.
Biomedical imaging applications typically assume a single material in a voxel when performing T1- and T2-measurements. Multi-compartment modeling may be used for simultaneously quantifying the T1- and T2-values for a limited number of tissue types that are assumed to be within a voxel. However, this approach works only for specific applications (e.g. myelin mapping in the human brain), requires prior knowledge about the disease and works only for a limited number of compartments.
In this context, according to a embodiment of the present invention the present invention provides a method for identifying at least one material comprised in a voxel, the method comprising the following steps:
A material can be considered to be a biological tissue, for example from a human, an animal or a plant. Alternatively or additionally the material can also be an object or material which has to be identified in a material analysis. Identifying a material can be considered to be a determination of the type of material or of the molecular composition of the material in the voxel, wherein the voxel defines a predefined volume unit at a predefined location in an object or the body. A radio-frequency pulse can be considered to be a magnetic field, especially an oscillating magnetic field, which is superimposed on or applied to the material of the voxel and which turns a magnetic spin of the material of the voxel into predefined directions. A time-domain-frequency-domain transformation can be considered a mathematical operation in which a signal is transformed from the time domain into the frequency domain. Thus, the signal is acquired in the time domain and is transformed in the frequency domain, which can also be understood as a spectral domain such that the time-domain-frequency-domain transformation can be understood as a time-domain-spectral-domain transformation. For example an inverse Laplace transformation or a Fourier transformation can be considered to be such time-domain-frequency-domain transformations.
In order to perform the invention explained in this description a signal train is measured using radio-frequency excitation pulses for example. Before the signal train, one or more radio-frequency preparation pulse may be applied to produce a pre-defined initial magnetization value of the sample (e.g. inverting the sign of the magnetization).
The present invention is based on the finding that said time-domain-frequency-domain transformation provides a very powerful tool to identify the material on the oasis of the first and second transformation values, which themselves are based on two steady-state-free-precession (SSFP) signal trains (or the combination thereof) which are measured when different radio-frequency pulses are exposed or applied to the material in the voxel. Due to the radio-frequency pulses, which differ in at least one parameter as for example in orientation, duration, or a strength of the oscillating magnetic field (resulting in a pre-defined flip angle), applied to the material in the voxel said transformation provides an efficient way in collecting information which can then be used and processed for the identification of the material of the voxel. The invention thus provides the advantage to identify the material very quickly with the minimum of necessary measurement information in contrast of state-of-the-art and with normal numeric effort.
According to a preferred embodiment of the present invention in the step of reading in, a second signal train is read in, in which the parameter of the radio-frequency preparation pulse exposed to the material in the voxel for measuring the second signal train differs in a amplitude, duration or a orientation from a radio-frequency preparation pulse exposed or applied to the material in the voxel for measuring the first signal train, especially in which the radio-frequency preparation pulse exposed to the material in the voxel for measuring the second signal train produces an inversion of the magnetization of the material. Such an embodiment of the present invention provides the advantage that those parameters can be easily measured respectively adjusted such that the identification of the material can be precisely accomplished with little technical effort. Furthermore, such a modification of the radio-frequency pulses has a significant impact on signals which are used for the identification of the material in the voxel.
Additionally or alternatively the parameter of the radio-frequency excitation pulse train exposed or applied to the material in the voxel for measuring the second signal train differs by the flip-angle of the radio-frequency excitation pulse train applied to the material in the voxel for measuring the first signal train. Such an embodiment of the present invention provides the advantage that those parameters can be easily measured respectively adjusted such that the identification of the material can be precisely accomplished with little technical effort. Furthermore, such a modification of the radio-frequency pulses has a significant impact on signals which are used for the identification of the material in the voxel.
According to a further embodiment of the present invention the step of performing comprises performing a time-domain-frequency-domain transformation of terms obtained by a summation and/or a subtraction of the first and second signal trains in order to obtain the first and second transformation values. Thus, the term used as a input for the transformation can be considered to be a sum or a difference of the first and second signal trains. Such a combination of the first and second signal trains prior to the performance of the transformation provides the advantage of an identification of the materials in the voxel based on analytical calculations.
Very little numerical effort has to be taken, if, according to a further embodiment, the step of performing comprises performing an inverse Laplace Transformation and/or a Fourier Transformation, and/or if the step of performing comprises performing a unidimensional time-domain-frequency-domain transformation. The performance embodiments using such a transformation provides the advantage of performing well known and thus numerically optimized transformation algorithms in order to obtain the first and second transformation values.
According to a further embodiment of the present invention the step of performing comprises at feast determining a local maximum of the first and/or second transformation value, especially determining a value, at which the local maximum of the first and/or second transformation value is obtained. Such an embodiment of the present invention provides the advantage that the determination of a local maximum of the first and/or second transformation value provides information on a time constant for the signal train approaching the steady-state after the material in the voxel is exposed to the radio-frequency excitation pulses and from which the identification of the material or the type of material in the voxel can uniquely be drawn. Thus, the local maximum provides a very strong information on determining a longitudinal relaxation value and a transverse relaxation value, which themselves provides an easy and precise identification of the material in that voxel.
In a further embodiment of the present invention, the step of performing comprises a calculation of a longitudinal relaxation value and a transverse relaxation value on the basis of the first and/or second transformation values, especially on the basis of a value, at which the local maximum of the first and/or second transformation value is obtained. Such an embodiment of the present invention provides the advantage of a precise and rapid identification of the material due to the fact that each material has unique values of longitudinal and transverse relaxation values, respectively a unique correlation of longitudinal and transverse relaxation values.
According to another embodiment of the present invention, the step of performing comprises computing an inverse or pseudoinverse of a matrix comprising information about different flip angles used for the radio-frequency excitation pulses applied to the material of the voxel. Such an embodiment provides the advantage of performing an algorithm which can be accomplished in a compact and numerically easy way such that the identification of the material in the voxel is determined quickly.
A very precise and rapid determination of the material in the voxel can be accomplished according to a further embodiment of the present invention in which the step of specifying comprises identifying the material on the basis of at least one correlation of a longitudinal relaxation value and a transverse relaxation value. The identification of the material can, for example, be performed on the basis of a comparison of the (measured or calculated) correlation of the longitudinal relaxation value and the transverse relaxation value with respect to a pre-defined correlation of longitudinal and transverse relaxation values which are, for example, taken from a lookup table. In this lookup table a specific correlation of the longitudinal relaxation value and the transverse relaxation value can be stored which then provides the basis for identification of the specific material under consideration. Therefore, such an embodiment of the present invention provides the advantage of a rapid and still precise determination of the material in the voxel.
Furthermore, the identification accuracy of the material can still be optimized, if according to a further embodiment of the present invention the step of specifying comprises identifying the material on the basis of a proton density value, being read in or being calculated from the first and/or second transformation values or values derived from the first and/or second transformation value. The proton density value provides further information which can be advantageously used for precise identification and determination of the quantity of the distinct material in the voxel. The proton density value can be read in for example from a specific sensor or be calculated from the values already determined or processed in the steps of the method disclosed herein.
In order to precisely determine the proton density of the material in the voxel, according to a further embodiment of the present invention the step of specifying comprises identifying the material on the basis of signal train values at the start (i.e. at time t=0 after the radio-frequency preparation pulses) and in the steady state of the signal train, the flip angle of the radio-frequency excitation pulses and the longitudinal and transverse relaxation values T1 and T2. The usage of such parameters of the present invention provides the advantage that these parameters can be easily measured or adjusted in a sensor device such that the identification of the material can be easily, rapidly and precisely accomplished.
Furthermore, the present invention also provides an apparatus being configured for performing, controlling or executing the steps of an embodiment of the here disclosed method in respective units.
The apparatus can presently be considered as an electrical device which is configured to process sensor signals and, dependency thereof, provide control and/or data signals. The sensor signals can for example be signals of a sensor of a medical device respectively of the sensor which is embedded in a medical device. The sensor signals can be considered the sensor signals of a magnetic resonance sensor. The control, data and/or sensor signals can be considered to be signals which are provided to a control or processing unit which is configured to perform the above-mentioned method in separate instances or subunits. Such subunits can, for example, be configured as signal processors or microcontrollers which are capable of performing mathematical algorithms.
Furthermore, an embodiment of the present invention implemented as a computer program project or computer program with program code provides advantages, wherein the computer program product or the computer program with program code is stored on a machine readable carrier for a storage medium as for example a semiconductor storage, a disk storage or an optical storage. The computer program product or the program with program code can be configured for performing and/or controlling the steps of the method according to a previously described embodiment of the present invention, especially if the program product or program is run on a computer or a respectively configured apparatus.
Embodiments of the approach presented here are described and depicted in detail with respect to the following figures and description. Shown is in
Same or equal elements are denoted by same or equal reference numerals, wherein a repeated description is omitted due to clarity reasons.
The apparatus 110 for identifying at least a material 115 in a voxel 120 comprises an interface or unit 125 for reading in, a unit 130 for performing and a unit 135 for specifying. The voxel 120 can be a volume unit of a predefined size and a predefined location of a human body 140 for example. The unit 125 for reading in is configured for reading in at least a first signal train S1 and a second signal train S2, wherein the first signal train S1 and the second signal train S2 each represent magnetization values of the materials in the voxel (120) which is measured by a (magnet field sensing) sensor 145. The first signal train S1 is specifically measured, after the material 115 in the voxel 120 was exposed to the predefined (first) radio-frequency pulse P1 being sent out from a first magnet emitter 150. The second signal train S2 is specifically measured, after the material 115 in the voxel 120 was exposed to the predefined (second) radio-frequency pulse P2, being sent out from the magnet emitter 150. In this context it is noted that the first radio-frequency pulse P1 differs in at least one parameter from the second radio-frequency pulse P2. For example, the first radio-frequency pulse P1 has a different duration, amplitude or orientation with respect to the magnetic field sent out as the second radio-frequency pulse P2. However as the second radio-frequency pulse P2 is sent out at a time interval after the first radio-frequency pulse P1 it is also possible that the second radio-frequency pulse P2 is sent out by the first magnet emitter 150 with different parameter settings as the sending of the first radio-frequency pulse P1 by the magnet emitter 150.
The apparatus 110 further comprises said unit 130 for performing. In this unit 130 for performing at least a time-domain-frequency-domain transformation is performed in order to obtain a first transformation value F1 and/or a second transformation value F0. The first transformation value F1 represents a frequency domain spectrum resulting from the time-domain-frequency-domain transformation on the basis of at least the first signal train S1. The second transformation value F0 represents a frequency domain spectrum resulting from the time-domain-frequency-domain transformation on the basis of at least the second signal train S2. However, the first transformation value F1 can be also obtained by said transformation on the basis of a combination of the first S1 and second S2 signal trains, for example a sum of the first and second signal trains. The second transformation value F0 can also be obtained by said transformation on the basis of a combination of the first and second signal trains, for example a difference of the first and second signal trains.
Finally, the apparatus 110 comprises said unit 135 for specifying the material on the basis of the first transformation value F1 and/or the second transformation value F0 or values derived from the first transformation value F1 and/or to second transformation value F0, in order to identify the material. To be more specific, the unit 135 for specifying is capable of detecting specific molecule or alloy as material in the voxel 120 in order to identify of the material.
The information of the identified specific material can then be output as a material signal 160, which can then be displayed at a respective display unit 165 in order to visualize the identified material in the voxel 120.
The present invention can also be accomplished for on the voxels located at the other positions in the body 140 as the voxel 120 according to
In the subsequently following paragraphs specific embodiments of the present inventions are disclosed in more detail.
Disclosed herein is a time-efficient data acquisition method and corresponding data analysis technique for measuring the correlated magnetic resonance (=MR) relaxation time parameters T1 and T2 of at least one material. The MR data acquisition method uses the transient phase of balanced steady-state free procession (bSSFP) measurements being accomplished by the sensor 145 shown in
In clinical magnetic resonance imaging (=MRI), the quantitative mapping of T1 and T2 constants offers several advantages over standard MRI. The quantitative information about T1 and T2 may allow for an improved biomedical diagnosis by identifying biomarkers of potential interest. Furthermore, quantitative MRI (qMRI) approaches are of special interest for multi-centric studies because the T1 and T2 values should not depend on the particular MR system on which they were acquired. So far, quantitative T1 and T2 mapping requires long measurement times and is not applied in clinical routine exams.
A very time-efficient qMRI approach is the inversion-recovery balanced steady-state free precession (IR-bSSFP) technique (also known as IR-TrueFISP) which allows to simultaneously acquiring 2D quantitative information about T1, T2 and relative proton density (M0) within a few seconds per slice. One major limitation of IR-TrueFISP and many other qMRI approaches is the assumption of a single material or tissue type within the volume of interest (also known as voxel). However, typically there exist several material components with different T1 and T2 values within one voxel (e.g. fat and water). The acquisition of correlated T1- and T2-distributions (i.e. T1-/T2-spectra) represents a more accurate way for identifying/characterizing different tissues or material types. The two axes of such a spectrum represent all possible T1 and T2 values and each individual peak in the correlated spectrum can be attributed to a unique T1-/T2-combination originating from a distinct material.
A widely used technique for measuring correlated T1-/T2-spectra is the inversion-recovery (IR) multi-spin-echo (MSE, also known as CPMG) method. However, multiple IR-CPMG measurements with different instrument settings (e.g. different times of inversion, TI) are required for obtaining accurate spectra. Due to the very long measurement times, the IR-CPMG approach is far from being applied in biomedical routine exams.
Instead, the IR-CPMG method is widely used for characterizing biological or synthetic materials such as plastic, oils or biological fluids. However, the long scan times prevent the application of IR-CPMG for inline testing which requires short measurement times to assure high throughput.
In summary, the acquisition of correlated quantitative T1 and T2 information allows for an accurate identification of multiple materials within a voxel. However, the long measurement times prevent clinical applications as well as inline material testing of synthetic or biological materials.
Here, an embodiment of the present invention is presented for fast MR relaxography that allows to generate correlated T1-/T2 spectra with only two measurements using the bSSFP (a.k.a. TrueFISP) sequence, an approach which is highly lime efficient compared to the state-of-the-art.
In bSSFP, radio-frequency (RF) excitation pulses are repeatedly applied with pre-defined amplitudes (e.g. to achieve a flip angle alpha=40°) and with constant time interval (repetition time, TR) of a few milliseconds (e.g. TR=4 ms) to produce a signal train. After several RF pulses, the signal train approaches a steady state. This phase of approaching the steady state is called transient phase and can be characterized by the following equation:
S
bssfp(t)=Sstst−(Ssisi−S0,start)·exp(−t/T1*) [Equation 1]
S0,start characterizes the initial signal at time t=0, Sstst is the steady-state signal and T1* represents the time constant for approaching the steady-slate. For a sufficient characterization of the transient phase, the duration of the signal trains should be on the order of 5-T1.
Assuming a single tissue type (i.e. a material according to the wording in the description of the inventive approach) within the voxel, it has been shown that the material parameters T1, T2 and M0 can be computed from Sstst, S0,start and T1*, for example when S0,start=−S0. Such a initial signal may be achieved by a magnetization preparation (as radio-frequency pulse) using an inversion RF purse. The relationship between the material parameters (T1, T2 and M0) and the measurement parameters derived from the signal train (S0, Sstst and T1*) are given by:
In principle, one may obtain a T1* spectrum from the measured signal train. To that end, according to one embodiment of the present invention the steady-state signal value is subtracted so that the magnitude of the signal represents a multi-exponential decay. Afterwards, a T1* spectrum may be obtained by applying the inverse Laplace transform to the resulting signal train. However, it is not possible to compute correlated T1- and T2-values from a single T1* spectrum, because S0 and Sstst cannot be obtained from a single spectrum. Instead, the amplitude of the peaks in such a T1* spectrum is a combination of both S0 and Sstst.
To be more specific, the relationship between a set of relaxation decay S(t) data and the relaxation time distribution F(T1) is known in the slate of the art by the integral equation:
S(tk)=∫T minT maxF(Ti)·K(tk, Ti)dTi
Here, tk is the time point for measuring the signal S(tk) and T1 may represent the relaxation time constants T1, T2 or T1*. Formally, this is a Laplace transformation. For the classic Laplace expression, the kernel K(tk, Ti) describes an exponential decay and has the form F(tk, Tl)=exp(−tx/Ti). However, other kernels can be used, for example for an inversion recovery experiment for T1 measurements, the kernel has the form F(tk, T1)−1-2·exp(−tk/T1). The relaxation time distribution F(Ti) can also be called a spectrum or probability distribution of relaxation rate constants Ri=1/Ti.
To obtain the relaxation time distribution F(Ti), the inverse Laplace transform (ILT) is used to solve the above mentioned equation. To that end, this above mentioned equation is typically converted into a system of linear algebraic equations by numerical integration and then solved using a non-negative least-squares fitting algorithm.
However, it has been realized that correlated T1- and T2-values can be obtained from only two measurements (N=2) with a bSSFP sequence. In the following, two implementations are described as specific embodiments of the present invention.
In the first implementation or embodiment, one measurement is performed with inversion RF preparation pulse and a second measurement is performed without inversion RF preparation pulse prior to the bSSFP sequence. Other sequence parameters are kept identical.
The signal train for the first measurement with inversion pulse is characterized by
S
1(t)=Sstst−(Sstst+S0)·exp(−t/T18) [Equation 3]
The signal train for the second measurement without inversion pulse is characterized by
S
2(t)=Sstst−(Sstst−S0)·exp(−t/T1*) [Equation 4]
One special aspect of an embodiment of the present invention is the combination of the measured signal trams. The summation of the first measurement (Equation 3) and the second measurement (Equation 4) yields:
S
sub(t)=S2(t)−S1(t)=2·S0·exp(−t/T1*) [Equation 5]
The signal train Ssub (t) depends only on Sstst, T1* and time t. The subtraction of the first measurement (Equation 3) from the second measurement (Equation 4) yields:
S
sub(t)=S2(t)−S1(t)=2·S0·exp(−t/T1*) [Equation 6]
The signal train Ssub(t) depends only on S0, T1* and time t. Afterwards, an inverse Laplace transform may be applied to the resulting signal trains to obtain two T1* spectra: the inverse Laplace transform applied to the signal train Sadd yields T1* as a function of Sstst and the inverse Laplace transform applied to the signal train Ssub yields T1* as a function of S0. In that way the parameters S0 and Sstst can be obtained for each T1* value allowing to compute the sought-after parameters M0, T1 and T2.
The basic data acquisition and processing steps according to the first embodiment of the present invention are schematically shown in
In the example in
This identification can be accomplished in a final step of specifying, in which the correlated T1- and T2-values for each component (respectively each material or at least one material) in the voxel under consideration can be computed according to Equations 2a-c and represented as a 2D spectrum, which is shown in
It is relevant to note, that spatial encoding can be applied by switching magnetic field gradients (as known from the state-of-the-art) between the RF-excitation pulses of the bSSFP sequence, e.g. using a Cartesian, a radial or a spiral readout. This allows to produce spatially resolved images at different time points during the transient phase.
In a second implementation or embodiment according to the present invention, two (or more) bSSFP signal trains are acquired where different excitation RF pulses that produce different flip angles α, are employed.
A magnetization preparation as for example performed by one or more radio-frequency preparation pulses Ppre (e.g. one inversion pulse or one saturation pulse) may be applied before acquisition of the signal trains. The basic idea is to make use of the fact that T1* depends on T1, T2 and the flip angle α produced by the excitation RF pulses
1/T*1=1/T1·cos2(α/2)+1/T2·sin2(α/2) [Equation 7]
For a series of N measurements (N>1) of different signal trains, this Equation can be rewritten:
1/T*1,n=1/T1·cos2(αn/2)+1/T2·sin2(αn/2) with n=1,2, . . . ,N [Equation 8]
For two bSSFP measurements with different flip angles α1 and α2, each material component will have two different T1* values within the corresponding T1* spectra. Because T1,n* can be determined from the spectrum (obtained from the corresponding signal train) and αn is known from the instrument settings, T1 and T2 can be computed, because in this case there are two Equations (T1,n* with n=1,2) and there are two unknowns (T1 and T2). In a more general way, Equation 8 may be rewritten in matrix form:
This matrix equation can be solved by computing the generalized inverse (pseudo-inverse, pinv) of the matrix T:
When T1, T2 and α are known, the relative proton density (M0) can be computed for each peak using the relationship:
Because the peak amplitude F(T1*) in a T1* spectrum is given by S0+Sstst, S0 can be obtained from:
Finally, by combining Equations 2c and 12 the relative proton density of a specific peak is given by:
Here, F is the measured peak amplitude in one T1* spectrum and the corresponding T1 and T2 values obtained from Equation 10.
The basic steps of the second embodiment of tho present invention can be summarized as follows:
Analogous to our first implementation, spatial encoding can be applied during the measurements try switching magnetic field gradients between the RF-pulses of the bSSFP sequence, e.g. using a Cartesian, a radial or a spiral readout.
The technical details of embodiments of the present invention can be mentioned as follows
The here disclosed method(s) allow(s) the quantification of correlated T1- and T1-values with only two measurements and represents a highly time efficient approach of identifying a material in a voxel. Compared to state-of-the-art IR-CPMG approach, the approach disclosed here is significantly faster and requires only several seconds scan time to produce correlated T1- and T2-values. Furthermore, the method is not based on a particular tissue model and therefore works for a wide range of biomedical applications at different organs.
The application fields of the proposed method are relatively broad and include e.g.
Number | Date | Country | Kind |
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17165079.9 | Apr 2017 | EP | regional |
Number | Date | Country | |
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Parent | PCT/EP2018/058435 | Apr 2018 | US |
Child | 16590019 | US |