Patent Description:
For anatomical and functional observations, high-field MRI is known and widely used. A reading magnetic field of more than <NUM>. 5T makes this technique particularly efficient.

However, in recent years, it has been shown that MRI can be performed with a weak reading magnetic field, well below the <NUM>. 5T, preferably around 50µT (i.e. of the order of magnitude of the earth magnetic field). This technique is currently limited to research works, for example in metabolic and molecular imaging.

Since the Signal to Noise Ratio - SNR is proportional to the intensity of the reading magnetic field, the SNR is very low for low field MRI.

It is thus necessary to rise the available magnetization of the water protons of a sample by a pre-polarization step, before the reading step. With the pre-polarization step, the magnetization of the sample is higher and the SNR of the reading signal obtained with a weak reading magnetic field is improved. Similarly, the contrast of the low field MRI image is improved by a pre-polarization step.

Two types of pre-polarization processes are known: the magnetic pre-polarization and the dynamic pre-polarization.

The magnetic pre-polarization is carried out by applying, for a short period of time, a pre-polarization magnetic field of higher intensity than the reading magnetic field. Placed in a stronger magnetic field, the population of the spins of the water protons acquires a greater polarization, which will result in a higher reading signal.

The dynamic pre-polarization is based on a transfer of magnetization from the electrons of the molecules of a contrast agent injected into the sample, towards the water protons surrounding these molecules. This transfer of magnetization is initiated by the saturation of the electronic transition layer of the molecules of the contrast agent through the application of an intense electromagnetic wave, at a predefined resonance frequency f<NUM>.

These steps of pre-polarization (magnetic or dynamic) and signal reading follow precise rules.

Consequently, known low field MRI systems are specifically designed to perform these steps in a specific manner. In particular, a low field MRI system exhibits a dedicated geometry to perform a magnetic pre-polarization or a dynamic pre-polarization step. In addition, the geometry is also dedicated to perform the reading step adapted to the pre-polarization step chosen and how this pre-polarization step is carried out. Such a low field MRI system is known for instance from <NPL>.

For example, the relatively high intensity required in the magnetic pre-polarization process has to be generated by one or several pre-polarization solenoid coil(s). However, this pre-polarization solenoid coil has to lay horizontally to allow the positioning of the sample inside the pre-polarization solenoid coil easily.

In addition, in order to maximize the reading signal at low reading magnetic field (and consequently at low frequency), it is recommended to use a reading solenoid coil, since such a coil maximizes the inductance and the filling factor.

But, to be able to place the sample inside the reading solenoid coil necessitates to align the long axis of the reading solenoid coil in a direction parallel to the long axis of the pre-polarization solenoid coil.

However, this requirement is in conflict with nuclear magnetic resonance principle, which implies that the transmitted and received electromagnetic Radio Frequency - RF field is always perpendicular to the direction of the reading magnetic field. Indeed, it would not be possible to position the antennas for the RF field in the proper direction taking into account the pre-polarization end reading solenoid coils.

In another example, it has been shown that a circularly polarized pre-polarization magnetic field increases the efficiency of the dynamic pre-polarization process, in particular when using this technique at ultra-low field. But such a magnetic field necessitates the use of a bird cage coil (or a similar coil with circular polarization capabilities), that can only be positioned horizontally to allow the sample to be easily positioned inside the bird cage coil. However, in order to carry out this circular polarization properly, it is then necessary that the main axis of the bird cage coil is aligned with the direction of a pre-polarization magnetic field that is beneficially created when the electronic saturation radio-frequency signal is applied.

The invention therefore aims at a low field MRI instrumental system with a greater versatility in order to exhibits different operating modes without being limited to one particular setup of the pre-polarization and/or reading steps.

To this end, the subject-matter of the invention is to provide a low field MRI instrumental system and methods of use of this low field MRI instrumental system according to the appended claims.

The invention and its advantages will be better understood upon reading the description which will follow, provided solely by way of example, with reference made to the accompanying drawings in which:.

As shown in <FIG> and <FIG>, the low field MRI instrumental system <NUM> according to the invention is capable of modifying the direction, and advantageously the intensity, of the magnetic fields during magnetization preparation and signal measurement.

A fixed frame of reference XYZ is attached to system <NUM>. The Z direction is parallel to the vertical direction of the laboratory where system <NUM> is located. XY plan is thus a horizontal plane. The X direction is chosen as the longitudinal direction of the cylindrical hollow volume going through system <NUM>. This hollow volume allows a sample <NUM> to be introduced along axis X into the low MRI instrumental system <NUM> so as to be placed inside an imaging predefined zone of view at the center of system <NUM>.

The low field MRI instrumental system <NUM> comprises, from the inside to the outside thereof:.

Each individual component <NUM> to <NUM> is known as such and the present low field MRI instrumental system <NUM> is specific in that it comprises component <NUM> (control/command unit <NUM> being adapted to be able to control component <NUM> in addition to the other components).

The low field unit <NUM> is designed to be able to generate a static magnetic field B0, whose direction can be selected, through unit <NUM>, in any direction and whose absolute intensity can be adjusted, through unit <NUM>, from zero to a maximum value of, for example, 200µT.

The low field unit <NUM> is made up of three sets of coils.

The first set of Helmholtz coils is designed and located to generate an elementary magnetic field along the X direction, the second set of Helmholtz coils is designed and located to generate an elementary magnetic field along the Y direction, and the third set of Helmholtz coils is designed and located to generate an elementary magnetic field along the Z direction.

Each set comprises at least one pair of Helmholtz coils. This particular embodiment is shown in the figures. To use several pairs of Helmholtz coils per set of coils, for example two pairs of Helmholtz coils, improves the homogeneity of the elementary magnetic field generated by this set of coils.

Each coil of a pair of coils is preferably square shaped. The two coils of a pair of coils are positioned symmetrically one form the other relative to a median plane of system <NUM>, orthogonal to the direction of the elementary magnetic field generated by this pair of coils.

The elementary magnetic field generated by one pair of Helmholtz coils is homogeneous at least inside the zone of view where the sample to be imaged is placed.

Each set of Helmholtz coils is thus positioned orthogonal to the two other pairs of Helmholtz coils.

The magnetic field B0 is the combination of the elementary magnetic fields generated by each set of coils.

Through the control of the intensity and the direction of the current flowing through each pairs of Helmholtz coils, it is possible to build up any magnetic field B0 in terms of direction and/or intensity, at least in the zone of view.

As shown in <FIG>, a first operating mode <NUM> of the low field MRI instrumental system <NUM> involves a magnetic pre-polarization process. This process consists in applying a strong static magnetic field (called pre-polarization magnetic field B_POL) in order to align the proton spins of the water contained in the sample preferentially along the direction of this pre-polarization magnetic field B_POL. Then, the pre-polarization magnetic field is switched off and the MRI measurement process takes place.

More specifically, <FIG> represents the time evolution of the intensity of the three components of the total magnetic field B in the zone of view, respectively BX, BY and BZ.

The first operating mode <NUM> comprises a first step <NUM> for the preparation of the sample.

A pre-polarization magnetic field B_POL is generated by the high field generator <NUM>. It is aligned with direction X, i.e. the axis of the hollow volume through system <NUM>.

During a first sub-step <NUM>, the solenoid coil of generator <NUM> is energized to bring the intensity of B_POL from zero to its target value, for example 20mT.

During a second sub-step <NUM>, the intensity of BPOL is maintained at its target value.

Finally, during a third sub-step <NUM>, the solenoid coil of generator <NUM> is de-energized to bring the intensity of BPOL back to zero. This step may be divided into two periods: in the first period, a rapid ramp down is applied to bring B_POL from its target value to a very low field level value, i.e. 1mT; then, in the second step, the decay of B_POL is slowed down to allow an adiabatic re-orientation of the magnetization from direction of B_POL during the pre-polarization step to the direction of B0_NMR during the reading step.

This first step spans during a pre-polarization time of for example <NUM>.

Then, the first operating mode <NUM> comprises a second step <NUM>.

It consists in imaging the sample in a low magnetic field.

A static magnetic field B0_NMR is generated by low field unit <NUM> along direction Z.

More specifically, during first sub-step <NUM>, unit <NUM> is energized to bring the intensity of B0_NMR from zero to its target value, for example of 205µT.

During a second sub-step <NUM>, the magnitude of B0_NMR is maintained constant at its target value.

At that time, the gradient generator <NUM> is controlled by unit <NUM> to superimpose magnetic components to the magnetic field B0_NMR for two or three dimension encoding for imaging purposes. In particular, a component along direction Z is added to get a reading magnetic field whose intensity in a point of the zone of view is specific to that point and other directional components
During this sub-step, one or several MRI measurements are performed iteratively. To this end, the electromagnetic LF antenna <NUM> is controlled by unit <NUM> to emit pulses and receive the response of the sample.

Each pulse is such that a dynamic magnetic field B1_NMR is generated along direction X with a frequency of for example around <NUM> at 205µT. After a duration TM, the response of the sample S_NMR to this pulse is also along direction X.

Finally, during third sub-step <NUM>, the unit <NUM> is de-energized to bring the intensity of field B0_NMR back to zero.

This second step spans during a measurement time of for example <NUM>.

First and second steps are iterated with a repetition time TR.

Advantageously, the sub-steps <NUM> and <NUM> are overlapping. The duration of each of these steps (also called field switching time) is of the order of <NUM>.

Advantageously, during both the first and second steps, unit <NUM> is controlled in order to generate a cancellation magnetic field, opposite the earth magnetic field so that this latter is totally cancelled.

As shown in <FIG>, in solid line, a second operating mode <NUM> of the low field MRI instrumental system <NUM> involves a dynamic nuclear polarization process under a linear polarized electromagnetic field.

The dynamic nuclear polarization process consists in applying a pre-polarization electromagnetic field in order to saturate the electronic spins transitions of the molecules of a contrast agent injected in the sample. Then, through the coupling between electronic spins and proton spins, the proton spins polarization of the water protons (<NUM>) of the sample increases under the influence of the strong electron spin polarization. The frequency of the pre-polarization electromagnetic field for the electron irradiation depends on coupling constants of the molecules and the applied B0_EPR magnetic field. Then the pre-polarization magnetic field is switched off and the IMR measures take place.

More specifically, the second operating mode <NUM> comprises a first step <NUM>.

A static pre-polarization magnetic field B0_EPR is generated by unit <NUM>. It is aligned with direction Z.

During the first sub-step <NUM>, the unit <NUM> is energized to bring the intensity of B0_EPR from zero to a first target value, for example 45µT.

During a second sub-step <NUM>, the intensity of B0_EPR is maintained constant at its first target value, while a dynamic pre-polarization magnetic field B1_EPR is generated along direction Y by EPR pulses generated by the electromagnetic RF antenna <NUM>. This operational mode is suitable for contrast agents having unpaired electrons, like nitroxides molecules, for example for Biomedical Overhauser Magnetic Resonance Imaging - OMRI purposes, using radiofrequencies ranging from <NUM> to <NUM> at least, with adapted RF antenna design.

This first step spans during a polarization time of for example <NUM>.

Then, the second operating mode <NUM> comprises a second step <NUM>.

During a first sub-step <NUM>, unit <NUM> is energized to build up the intensity of the static magnetic field B0_NMR along direction Z. Unit <NUM> brings the magnitude of the static magnetic field B0 from its first target value at the end of the first step <NUM> (45µT) to a second target value, for example of 205µT. The direction of the static magnetic field B0 is thus unchanged between the first and second steps.

During a second sub-step <NUM>, the magnitude of B0_NMR is maintained constant at its second target value.

The gradient generator <NUM> is controlled by the unit <NUM> to superimpose magnetic components to the magnetic field B0_NMR to get suitable encoding and reading magnetic fields.

During this sub-step, one or several MRI measurements take place. To this end, the electromagnetic LF antenna <NUM> is controlled by unit <NUM> to emit pulses B1_NMR and receive the corresponding responses S_NMR of the sample.

The pulses are such that a dynamic magnetic field B1_NMR is generated along direction X with a frequency of for example around <NUM> at 205µT.

Finally, during a third sub-step <NUM>, the unit <NUM> is de-energized to bring the intensity of B0_NMR back to zero.

Advantageously, during both the first and second steps, unit <NUM> is operated so as to generate a cancellation magnetic field opposite the earth magnetic field so that this latter is cancelled.

In this second operating mode there is no modification of the direction of the static magnetic field used both for pre-polarization B0_EPR, and for measurement, B0_NMR.

As shown in <FIG>, a third operating mode <NUM> of the low field MRI instrumental system <NUM> also involves a dynamic pre-polarization process, but performed under a circular polarized electromagnetic field.

More specifically, the third operating mode comprises a first step <NUM>.

A static pre-polarization magnetic field B0_EPR is generated by unit <NUM>, but this time this static magnetic field is directed along direction X.

During a first sub-step <NUM>, the unit <NUM> is energized to bring the intensity of B0_EPR from zero to its target value, for example 45µT.

During a second sub-step <NUM>, the intensity of B0_EPR is maintained constant at its target value, while a dynamic pre-polarization magnetic field B1_EPR is generated. Field B1_EPR is created by the electromagnetic RF antenna <NUM> emitting EPR pulses.

The dynamic pre-polarization magnetic field B1_EPR is generated so that it has a component B1_EPR_Y along direction Y and a component B1_EPR_Z along direction Z.

The pulses are controlled to have a phase difference of <NUM>° between the Z and Y components so that the dynamic field B1_EPR turns in the ZY plane, i.e. the plane orthogonal to the direction of the static field B0_EPR. B1_EPR thus is circularly polarized.

This operational mode is suitable for contrast agents having unpaired electrons, like nitroxides molecules, for OMRI purposes, using radiofrequencies ranging from <NUM> to <NUM> at least, with adapted RF antenna design.

Finally, during a third sub-step <NUM>, unit <NUM> is de-energized to bring the intensity of the static field B0_EPR back to zero.

The third operating mode comprises a second step <NUM> similar to the reading step <NUM> of the second operative mode.

During a first sub-step <NUM>, unit <NUM> is energized to build up the intensity of the static magnetic field B0_NMR along direction Z. Unit <NUM> brings the magnitude of the static magnetic field B0 from its value at the end of the first step <NUM> (45µT) to its target value, for example of 205µT, while modifying the orientation of the direction of this static magnetic field B0 from direction X to direction Z.

The gradient generator <NUM> is controlled by the unit <NUM> to superimpose a magnetic component to the static magnetic field B0_NMR to get a suitable reading magnetic field as previously described.

During this sub-step, one or several MRI measurements take place. To this end, the electromagnetic LF antenna <NUM> is controlled by unit <NUM> to emit LF pulses and receive the corresponding responses from the sample.

The LF pulses are such that a dynamic magnetic field B1_NMR is generated along direction X with a frequency of around <NUM> at 205µT.

Finally, during a third sub-step <NUM>, the unit <NUM> is de-energized to bring the intensity of the static field B0_NMR back to zero.

Advantageously, during both the first and second steps, unit <NUM> is operated in order to generate a cancellation magnetic field that is opposite to the earth magnetic field to cancel this latter.

Advantageously, the sub-step <NUM> and <NUM> are overlapping. This field switching time is of the order of <NUM>. The field switching is preferably adiabatic and the magnetization vector of the sample rotates according to the resulting static field orientation.

In this third operating mode, there is a modification of the direction of the static magnetic field between the pre-polarization step and the measurement step.

Other operating modes of the system according to the invention may be encompassed by the person skilled in the art.

For example, the static magnetic field in the reading step could be oriented along direction Y rather than direction Z.

In another example, rather than kept constant during the reading step, the value of the static magnetic field may be changed, for example, by stages, one or more measures taking place at each stage.

The low field MRI instrumental system is very versatile in its uses, since it is provided with a plurality of sets of coils allowing the selection and the setup of the direction and intensity of the static magnetic field.

Claim 1:
A low field Magnetic Resonance Imaging - MRI instrumental system (<NUM>) for imaging a sample (<NUM>) placed inside a hollow cylindrical volume through the low field MRI instrumental system (<NUM>), comprising:
- an electromagnetic Radio Frequency - RF antenna (<NUM>) adapted to emit electromagnetic RF pulses for inducing Electron Paramagnetic Resonance - EPR;
- an electromagnetic Low Frequency - LF antenna (<NUM>) for measurements, adapted to emit electromagnetic LF pulses for inducing Nuclear Magnetic Resonance - NMR, respectively to receive LF signal produce by NMR;
- a gradient generator (<NUM>), adapted to create a gradient in a static magnetic field generated during measurements;
- a high field generator (<NUM>) adapted to generate, in the hollow cylindrical volume, a strong pre-polarization magnetic field for magnetic pre-polarization; and,
- a control/command unit (<NUM>),
characterized in that the low field MRI instrumental system (<NUM>) further comprises a low field unit (<NUM>) adapted to generate, inside the hollow cylindrical volume, a low static magnetic field whose direction is adjustable in any direction in space, a fixed reference frame XYZ being associated with the low field MRI instrumental system (<NUM>) so that the direction X coincides with a main axis of the hollow cylindrical volume through the low field MRI instrumental system (<NUM>), wherein the strong pre-polarization magnetic field is of higher intensity than the low static magnetic field.