A nuclear magnetic resonance device and method of use therefor

Abstract

The present invention relates to the provision of a nuclear magnetic resonance (NMR) device, suitable for measurement of NMR signals within a body part of a subject. The present invention provides a light weight and portable nuclear magnetic resonance (NMR) device, suitable for measurement of NMR signals using a plurality of magnets arranged in an array to create a first inhomogeneous magnetic field (B0) having a B0 static field gradient; a plurality of radio frequency coils arranged to create an individual inhomogeneous magnetic field (B1) substantially perpendicular to the first inhomogeneous magnetic field (B0), the plurality of radio frequency coils configured to create a plurality of different radio frequencies and bandwidths; and acquisition means to acquire NMR signal data from the different bandwidths within the B0 and B1 gradients and to process the magnetic resonance signal data to provide spatial localisation. Methods of NMR data collection and diagnosing a brain injury are also provided.

Description

[0001] A Nuclear Magnetic Resonance Device and Method of Use Therefor

[0002] Field of the Invention

[0003] The present invention relates to the provision of a nuclear magnetic resonance (NMR) device, suitable for measurement of NMR signals within a body part of a subject.

[0004] Background

[0005] Conventional nuclear magnetic resonance imaging devices (also known as Magnetic Resonance Imaging devices (MRI)) are large, expensive and located in specialist hospitals or imaging facilities. These traditional devices require trained technical staff, and the subject requiring the imaging has to go to the device for imaging. If a subject is immobile or experiencing a medical event, such as a stroke, movement of the subject may be unsafe. With these limitations, oftentimes a subject is not diagnosed quickly enough, and treatment may be delayed.

[0006] It is an object of the present invention to overcome some of these limitations or to at least provide the public with a useful alternative.

[0007] Summary of the Invention

[0008] In one aspect the present invention provides a nuclear magnetic resonance (NMR) device, suitable for measurement of NMR signals within a target region of a body part of a subject, including:

[0009] (a) a plurality of magnets arranged in an array, the magnet array being configured to receive the body part of the subject; the magnet array being configured to create a first inhomogeneous magnetic field (Bo) having a Bo static field gradient within the body part of the subject under examination; wherein the magnet array comprises a plurality of spaced apart magnet rings, each ring configured to extend about the body part;

[0010] (b) a plurality of radio frequency coils arranged in an array and configured between the magnet array and about the body part of the subject, in use, each coil configured to create an individual inhomogeneous magnetic field ( B ) substantially perpendicular to the first inhomogeneous magnetic field (Bo), the plurality of radio frequency coils configured to create a plurality of different radio frequencies and bandwidths across the volume of the body part of the subject; and

[0011] (c) acquisition means to acquire NMR signal data from the different bandwidths within the Boand Bi gradients and to process the magnetic resonance signal data to provide spatial localisation across the volume of the body part; (d) wherein the configuration of the magnet array and the radio frequency coil array is such to ensure that the Bo and B2fields provide coverage over substantially all the volume of target region within the body part within the device.

[0012] In one example, the magnet array may comprise a plurality of spaced apart yokes, each yoke supporting at least a pair of spaced apart magnets, the yokes and magnets being arranged in an array whereby the magnets define a ring that defines a bore within the device.

[0013] In one example, the spaced apart yokes may be linear and each support at least a pair of magnets. In one example, the spaced apart yokes may be substantially curved around the magnet array to form the magnet ring.

[0014] In one example, the device may have three or more magnet rings.

[0015] In one example, the radio frequency coil array comprises a plurality of coils configured into an arrangement to extend between the magnet array and about the body part, the radio frequency coil array being configured to provide spatial information across the volume of the target region.

[0016] In one example, each radio frequency coil is sensitive to radio frequencies spins within a particular sector of the bore.

[0017] In one example, the radio frequency coil array is configured to provide a transmit-only coil, and a plurality of receive-only coils.

[0018] In one example, the radio frequency coil array is configured to provide a plurality of radio frequency coils that can transmit and receive.

[0019] In one example, the plurality of radio frequency coils are configured to transmit simultaneously.

[0020] In one example, the plurality of radio frequency coils are configured to receive simultaneously.

[0021] In one example, the cross section of the bore defined by the magnet rings may be substantially elliptical.

[0022] In one example, the side profile of each of the magnet rings may be non-planar.

[0023] In one example, the magnets in the array may be irregularly spaced apart.

[0024] In one example, the magnet array may be configured to provide a first controlled inhomogeneous magnetic field (Bo) has a field strength of about 80 mT to about 120 mT, preferably about 100 mT, within the bore. In one example, the magnet array may be configured to provide a gradient of magnetic field across the target region of about 15mT to about 20mT.

[0025] In one example, the device is portable. In one example the portable device may weigh less than about 30 kgs, preferably less than about 25 kgs.

[0026] In one example, the body part may be a head of the subject and in another example, the subject may be a human.

[0027] In another aspect a method for NMR data collection using a device as provided above, the method including the steps of:

[0028] (a) applying a controlled inhomogeneous magnetic field Bo across a volume of a target region of a body part of a subject to generate a series of acquisition bands with different resonant frequencies;

[0029] (b) exciting nuclear spins within each acquisition band among a set of acquisition bands that collectively cover the target region of the body part by means of radio frequency pulse generation and transmission from a plurality of radio frequency coils to cause the spins to generate a plurality of unique radio frequency signals;

[0030] (c) receiving the plurality of unique radio frequency signals emitted by the nuclear spins from the acquisition bands that collectively provide spatial information across the target region of the body part by using the unique spatial sensitivity of each radio frequency coil; and

[0031] (d) processing the received radio frequency signals to provide data representing the magnetic resonance property(ies) of the target region.

[0032] In a further aspect, there is provided a method of diagnosing a brain injury using a device as defined above, the method including the steps of

[0033] (a) applying a controlled inhomogeneous magnetic field Bo across a volume of a head of a subject to generate a series of acquisition bands with different resonant frequencies;

[0034] (b) exciting nuclear spins within each acquisition band among a set of acquisition bands that collectively cover the head by means of radio frequency pulse generation and transmission from a plurality of radio frequency coils to cause the spins to generate a plurality of unique radio frequency signals;

[0035] (c) receiving the plurality of unique radio frequency signals emitted by the nuclear spins from the acquisition bands that collectively provide spatial information across the head by using the unique spatial sensitivity of each radio frequency coil; and (d) processing the received radio frequency signals to provide data representing the magnetic resonance property(ies) of the target region; and

[0036] (e) interpreting the data to diagnose the presence or otherwise of a brain injury.

[0037] In one example, the brain injury may be an ischemic stroke.

[0038] In one example, the brain injury may be a haemorrhagic stroke.

[0039] In one example, the brain injury may be neonatal hydrocephaly.

[0040] In the methods defined above, in one example in step (d) the data representing the magnetic resonance property(ies) of the target region may be further processed into an image.

[0041] In the methods defined above, in one example, steps (a) to (d) may be carried out in less than about 20 minutes; or less than 15 minutes or less than about 10 minutes.

[0042] In the methods defined above, in one example, the independent signals may be received using at least a plurality of radio frequency coils simultaneously.

[0043] In the methods defined above, in one example, in step (b) the radio frequency pulses generated may have an excitation bandwidth of about 40 kHz to about 60 kHz.

[0044] In the methods defined above, in one example, in step (a) the series of acquisition bands generated may comprise at least 5 acquisition bands.

[0045] In the methods defined above, in one example, the magnetic resonance property of the target region may be diffusion.

[0046] In the methods defined above, the magnetic resonance property of the target region may be perfusion.

[0047] In the methods defined above, the magnetic resonance property of the target region may be T2.

[0048] In the methods defined above, the body part may be a head of the subject.

[0049] In the methods defined above, the subject may be a human.

[0050] In the methods defined above, in one example, the method may be performed in a setting remote from a hospital.

[0051] The present disclosure is described below with reference to specific examples. However, other examples than the above described are equally possible within the scope of the disclosure. Different method steps than those described, performing the method by hardware or software, may be provided within the scope of the disclosure. The different features and steps of the disclosure may be combined in other combinations than those described.

[0052] Further aspects of the disclosure will become apparent from the following disclosure.

[0053] In this specification, where reference has been made to external sources of information, including patent specifications and other documents, this is generally for the purpose of providing a context for the description of the features described. Unless stated otherwise, reference to such sources of information is not to be construed, in any jurisdiction, as an admission that such sources of information are prior art or form part of the common general knowledge in the art.

[0054] Definitions

[0055] As used herein, the term "bore" in connection with the device means the volume within the device, in particular, the volume that receives a body part.

[0056] As used herein, the term "about" in connection with a referenced numeric indication means the referenced numeric indication plus or minus up to 10% of that referenced numeric indication. For example, the language "about 30" kgs covers the range of 33 kgs to 27 kgs.

[0057] As used herein the term "and / or" means "and" or "or", both. As used herein "(s)" following a noun means the plural and / or singular forms of the noun. The term "comprising" as used in this specification means, "including" or "consisting at least in part of". When interpreting statements in this specification which include that term, the features prefaced by that term in each statement all need to be present, but the other features can also be present. Related terms such as "comprise" and "comprised" are to be interpreted in the same matter. The entire disclosures of all applications, patents and publications, cited above and below, if any, are hereby incorporated by reference.

[0058] As used in this specification, the terms "comprises", "comprising", "includes", and "including" are to be construed as being inclusive and open-ended rather than exclusive. Specifically, when used in this specification, including the claims, the terms "comprises", "comprising", "includes", and "including" and variations thereof mean that the specified features, steps, or components are included. The terms are not to be interpreted to exclude the presence of other features, steps, or components.

[0059] The term "approximately" or "approximate" as used herein, means nearly or near to, or about, or close to. Alternatively, "approximately" or "approximate" means estimated, or inexact.

[0060] The term "substantially" as used herein, means for the most part, or mostly, or essentially, or to a great or significant extent.

[0061] DRAWING DESCRIPTION One or more examples of the disclosure will be described below with reference to the accompanying drawings, in which:

[0062] Figure 1 is a perspective view of an NMR device shown schematically having a subject's head located within the bore.

[0063] Figure 2 shows a further perspective view of an NMR device with a cut away section of magnets showing schematically the location and proximity of the radiofrequency coils relative to the magnets and the subject's head located within the bore.

[0064] Figure 3 shows a schematic view of a series of spaced apart magnet rings that together form the magnet array.

[0065] Figure 4 (a) shows a top view of a magnet ring array having an elliptical arrangement.

[0066] Figure 4(b) shows side view of a magnet ring array having a planar arrangement.

[0067] Figure 4(c) shows a magnet ring array having a non-planar arrangement.

[0068] Figures 5(a) and 5(b) show a cross sectional view of a spaced apart pair of magnets at each end of a yoke the magnets together providing a magnetic field depicted by Bo and the radio frequency coil providing a substantially perpendicular field Bi.

[0069] Figures 6(a) to 6(e) show plots of magnetic field strength in different planes. 6(a) shows the magnetic field strength in the XZ plane. 6(b) shows the magnetic field strength in the YZ plane. Figures 6(c), 6(d) and 6(e) show the magnetic field strength in the XY plane and different heights.

[0070] Figure 7 shows the magnetic field strength along the X axis with 5 different magnet ring radii ranging from 110mm to 130mm.

[0071] Figure 8 (a) shows a three-dimensional view of a radio frequency array of having several radio frequency coils.

[0072] Figure 8(b) shows a two-dimensional plan view of a radio frequency array of having several radio frequency coils.

[0073] Figures 8(c) to 8(f) all show plots of radio frequency strength from individual coils across the bore and in different planes.

[0074] Figures 9(a) to 9(d) show plots in different planes showing the regions where an ischemic stroke is likely to occur. Figure 10 shows a pair of acquisition bands generated by a magnet array (a) and (c) and showing their respective target region coverage in a corresponding pair of heatmap slices (b) and (d).

[0075] Figure 11 shows a series of acquisition bands acquired from a number of radio frequency coils for different sectors across the target region / brain.

[0076] Figure 12 shows a plot of simulated diffusion weighted signal difference between left and right hemispheres for patients with ischemic regions.

[0077] Figure 13 shows a rendering of a portable NMR device containing a magnet array and radio frequency coils as described herein.

[0078] DETAILED DESCRIPTION

[0079] A magnet array 1, suitable for a nuclear magnetic resonance (NMR) system is shown in Figure 1. A magnet array 1 is configured and shown as receiving a cranium 2 of a subject. The magnet array includes a framework configured to define a bore into which a body part, such as a cranium of a subject is located, when in use. The framework comprises one or more spaced apart rings 3 and 4 to support a plurality of magnets 5 in an array configured into two or more concentric rings (as shown in Figure 3), each ring being spaced apart and secured by a plurality of yokes 6 that position the concentric rings in a spaced apart manner and each yoke 6 supporting one or more magnets to form the magnet array 1.

[0080] The magnet array 1 is combined with a series of radio frequency (RF) coils 7 arranged between the magnet array and the cranium, when in use to form the nuclear magnetic resonance (NMR) system. The radio frequency coils 7 are best shown in Figure 2.

[0081] With reference to Figure 3, an alternative example is illustrated showing a magnet array configured into three spaced apart magnet rings 8, 9, 10 each ring comprising spaced apart magnets 5 are shown. The distance between each magnet ring is known as the z-spacing distance. This magnet array example differs from the magnet array example shown in Figures 1 and 2 by including an inner ring 9 of magnets.

[0082] With reference to Figure 4, the magnet array is configured into an elliptical shape see Figure 4(a) having a planar side section (see Figure 4(b). However, it is to be appreciated that any shape that encircles a target region may be used and that a non-planar side section (See Figure 4(c)) may also be suitable depending on the shape of the target region.

[0083] NMR systems use a constant magnetic field Bo provided by magnet arrays, in this example, but also rely on a weaker oscillating field Bi. This oscillating field is provided by a series of radiofrequency coils, such as coils 7 of the magnet array, which is used to generate Bi magnetic field in order to excite the spins and detect signals from spins.

[0084] The homogeneous Boand B field in conventional NMR and MRI systems (combined with pulsed gradients) can excite, detect and spatially localise NMR signals from nuclear spins within the NMR system. In contrast, the NMR system as configured and described herein makes measurements in the inhomogeneous field produced by its Bo magnet array. Spins are on-resonance when their resonant frequency, which is dependent on Bo at their location, falls within the excitation frequency bandwidth of the Bi field. Spins that are off-resonance are substantially not sensitive to the excitation from the Bi field. Therefore, measurements in an inhomogeneous Bo field are limited by the Bi excitation frequency and bandwidth, which limits the coverage region: the region where signals can be excited and detected. However, the spatial sensitivity of the described NMR device has been configured through the design of the magnet array and RF coil array to ensure that the Bo and Bi fields still enable coverage of substantially all the volume of target regions within the device.

[0085] Furthermore, the device is configured to minimise mass and improve the efficiency of the magnet array: the strength of the magnetic field inside the bore per weight of magnet array. It is important to configure the magnet array to maximise the strength of the Bo field, because the strength of the NMR signal is dependent on the field strength. However, the weight of the device is an important consideration for the portability of the device, particularly in pre-hospital or in-field environments. Decreasing the weight is desirable because it makes the device easier to transport and use. By design and optimisation of the number, size, position of the magnets in the magnet array (as discussed below in Example 1), the efficiency of the design is improved while maintaining coverage across the target regions.

[0086] With reference to Figures 5(a) and 5(b), a cross sectional view is provided of one magnet pair 11 positioned on yoke 12 showing an optional inner magnet 13. Curved lines 15 denote the contours of the Bo magnetic field strength extending between the magnets, the magnetic field direction being shown by arrow Bo. The magnetic field strength decreases as the lines moves away from the magnet creating a static magnetic gradient. The Bo magnetic field extends over the target region, the shaded area in the centre 16. Figure 5(b) shows the effect of the additional magnet ring 17, which is configured to straighten the contours of the Bo magnetic field strength 15 across the target region. The magnet array and RF coil assembly provide a multitude of these arrangements in the overall device. In the example illustrated in Figure 1 there are 18 pairs of magnets that each produce their own magnetic fields. A RF coil 14 is shown positioned between the magnets and spaced apart from the magnets and yoke. The oscillating magnetic field Bi is generated by the current flowing through the RF coil and is substantially perpendicular to Bo. This arrangement has been determined to be a substantially optimised arrangement. It is to be understood that each RF coil is positioned independently of the magnetic pairs and what is illustrated in Figure 5 is to be understood as a simplification of the overall device.

[0087] The magnetic field coverage is dependent on the inhomogeneous Bo and B2fields produced by the magnet array and RF coils. The inhomogeneous Bo field forms a controlled gradient across the bore, where spins at different locations experience a range of Bo field strengths, which correspond to a range of resonant frequencies. Making multiple NMR measurements with a range of B2frequencies and bandwidths, that correspond to different locations across the bore, allows the device to excite and detect signals from multiple different regions across the inhomogeneous Bo field, increasing coverage. This controlled gradient or controlled inhomogeneous magnetic field Bo is necessary to achieve the functionality of the NMR system.

[0088] In addition to the magnet array and RF coil array, additional hardware is required to acquire the NMR signals from spins in the bore. This includes a spectrometer to execute NMR pulse sequences (for example those supplied by Resonint, Wellington NZ) and RF amplifiers for transmit and for receive (for example, those supplied by TOMCO, Stepney, SA Australia). This hardware is similar to the electronics used in other low-field NMR instruments. The spectrometer handles timing within the pulse sequence, produces RF pulses of varying frequencies, powers and duration and acquires the NMR signals. The spectrometer may operate in a multi-channel mode, acquiring RF signals from all RF coils simultaneously, or operate in a multiplexed mode, where only signals from a subset of the RF coils are acquired simultaneously.

[0089] With reference to Figure 13 an example of a commercial NMR device envisaged is shown. The Device is encased in a housing with hand grips to allow for ease of portability. The device may also include one or two windows to allow a user to look out of the device for more comfort and to reduce what may be a sense of claustrophobia.

[0090] Example 1 Magnet Array Simulation Example

[0091] The Bo magnetic field produced in the magnetic array described above defines the spatial sensitivity and coverage of the system. To understand the efficiency and gradient produced by different types of magnet array designs), a range of magnet assemblies of various designs were produced and the magnetic field they produced was simulated. A range of parameters such as number of magnets, magnet size, ring diameter, eccentricity, and z-spacing were tested in each design to understand how they affected the field strength and gradient. These parameters were used to produce a list of magnet positions and magnetisation directions that were used as inputs for the simulation process.

[0092] In the method chosen, the Finite Element Method (FEM) method, the full geometry of the magnet array was generated, including the shape of the magnet blocks and yoke pieces. The simulation used the open source gmsh / GetDP software. This produced a 3-dimensional volume of the magnetic field, from which the magnitude was calculated as the Bo magnetic field.

[0093] The geometry was meshed using the software gmsh and the coercive field, remanent magnetisation and magnetic permeability for the magnet and yoke regions was set using the material properties. The field was solved using the software package GetDP, using the scalar magnetic potential method.

[0094] This method was used because it simplified the analysis while capturing the effect of changing material permeability. The magnetic field was calculated and was then interpolated onto a regular grid producing a 2D map, or 3D volume of the magnetic field across the bore.

[0095] It was determined that the most efficient design with an axial field found was the in-out ring or Aubert ring design, modified to add a yoke connecting the main rings. This design produced a radial magnetic field gradient, with the field weakest along the bore axis at r=0 and increasing with r inside the bore. The results from this design in relation to the magnetic field strength is shown in the series of contour plots in Figure 6.

[0096] The magnet array was based around two magnets rings to define a bore, with additional magnet rings in between to further alter the magnetic field as desired. One of the main rings has blocks arranged with magnetisation pointing radially out from the bore axis, and the other with blocks with magnetisation towards the bore axis as shown in Figure 3. These magnet rings produced a magnetic field inside the array which was oriented along the bore axis z as shown in Figure 3.

[0097] There may also be 1 or 2 additional magnet rings between the in-out magnet rings, which further control the magnetic field gradient inside the bore. The magnets in the additional rings were magnetised pointing to -z, to augment the field strength inside the bore. The magnet size may be changed depending on the desired magnetic field gradient. Preferably, the magnets were the same size or smaller than the in-out ring magnets, to avoid decreasing the bore size.

[0098] Additionally yoke bars of high permeability metal such as steel connect the in-out rings, creating a yoke that redirected and concentrated the magnetic field on the inside of the bore. This increased the field strength inside the bore, the efficiency of the magnet array and further, reduces stray magnetic field outside of the device. It also provided mechanical support for the in-out rings. With the in-out magnet ring design, it was observed in the various designs simulated that increasing the diameter decreased the field strength inside the bore (for the same number of magnets.) This trend was to be expected because the magnetic field produced by the same volume of magnets is spread over a larger volume. This suggested a smaller bore volume would have provided higher efficiency, however the body part to be measured still limited the minimum size of the bore.

[0099] It was also determined that stretching the magnet rings into an ellipse-like shape along the y-axis helped to maintain field strength and coverage, as well as minimising the x-axis diameter and enclosed bore volume. This was desirable because the preferred body part to be studied within the bore volume is a cranium where the cranium length is typically longer than the cranium breadth, meaning that the front-back length is longer than the left-right width. To fit a cranium within the bore, the larger dimension limits the minimum size of the device. Surprisingly it was found that stretching the magnet rings along the y-axis helped to maintain field strength and coverage, as well as minimising the x-axis diameter and enclosed bore volume.

[0100] It was also found that the ring z-spacing affected the magnetic field strength and the magnetic field gradient. For a pair of in-out magnet rings, the maximum field strength and efficiency was obtained when the z-spacing was substantially equivalent to the magnet ring diameter. However, this also significantly increased the radial gradient, limiting the magnetic field coverage. Making the z-spacing larger than diameter decreased the radial gradient, at the cost of field strength. This parameter was determined to be important for controlling the coverage of the system.

[0101] A further parameter of interest was the shape of the rings along the y-axis. While this may be a flat plane, with the z position constant along y as in Figure 4(b), the effect of distorting the z position of the magnets along the front-back axis to follow the contour of the target region was also investigated. The contour may be obtained by averaging the shape of the target region, or alternatively the magnet ring position distorted by a mathematical expression such as y = cz*z2for y<0. This describes a plane with a curved region towards the back of the magnet ring, improving coverage of the target region.

[0102] Further optimisation of the magnet array may include the variation of magnet spacing around the ring, for example increasing the space between adjacent magnets in a ring, or excluding one or more magnets from certain positions in the ring. This may allow further reduction in weight and increased patient comfort by reducing claustrophobia.

[0103] Depending on the magnet ring z-spacing, the magnetic field contains an ellipse with a maximum of Bo. A saddle point was observed - see dashed line 19 in Figure 6(d), where the magnetic gradient is substantially zero. It was determined that to ensure a consistent magnetic gradient covered the bore volume and target region, that the saddle point and beyond had to be outside of the bore volume or any region of interest.

[0104] Because the ring z-spacing was large compared to the size of the magnets, the addition of inner magnet rings (9 in Figure 3) in the space between the in-out rings (8,10 in Figure 3) was also investigated. These are magnetised along the z axis to increase the field strength inside the array. Designs with a yoke constrain the inner rings to be smaller than the main in-out rings. The number of rings and their position was free to vary. It was observed that adding 1 or 2 rings of smaller magnets intermediate the outer magnet rings provided a way to control the field gradient, particularly on the edges of the target region / bore. By controlling the radius of the inner magnet rings, the gradient across the target region can be made more constant thereby removing any effect from the field strength maximum ring referred to above.

[0105] Another consideration taken into account in the magnet array design was the shape of the magnetic field contours and gradient. As discussed below in Example 3, the inhomogeneity of the Bo field was used to select spins from different radial depths inside the bore. This technique enabled NMR signals to be localised to different radii by changing the B2excitation frequency. The contours of the Bo magnetic field strength, illustrated by 15 in Figures 5 (a) and (b), reflect the volume of spins that are excited at each excitation frequency and that form the acquisition bands, as shown in Figure 6 for example.

[0106] In addition to maintaining coverage over the target region (16 in Figures 5 (a) and (b)), it was important to control the shape of these contours of each acquisition band. This was because highly curved acquisition bands made it harder to localise the detected NMR signals in the radial direction. In a curved acquisition band, the radius of the acquisition band is dependent on z, which may make it difficult to localise the signal to a single radius. It was preferable to design the magnet array so that the field contours are substantially straight across the target region. This may be achieved by adding more magnet rings above the top of the magnet array, enclosing one side, as illustrated by 17 in Figure 5 (b). The additional magnet rings appeared to augment the field in the top half of the bore, straightening the magnetic field contours across the target region.

[0107] Example 2 Coil Simulation Example

[0108] In another example, the contribution to the coverage of the device from the inhomogeneous B2fields produced by the array of RF coils was simulated. Each coil has a sensitivity pattern which reflects its sensitivity to spins in different locations, due to the inhomogeneous B2it produces. The Bi fields produced by these coils were simulated using the Biot-Savart law (see Griffiths). The low radio frequency Bi meant the coil current can be treated as quasi-static. The RF coil array was defined parametrically to control the position and size of the RF coils. It was therefore determined that a series of elliptical wire paths around the surface of an elliptical cylinder to fit around edge of the bore was optimal as shown in Figure 8(a) and 8(b).

[0109] As in the Bo design, the radiofrequency field produced by each coil was calculated on a grid of points to simulate a 3D image of the Bi field produced by each RF coil with a current of 1 Amp. Slices of the 3D image are shown in Figures 8(c) and 8(d). The Bi field magnitude on the xy plane was used, because this controls the spatial sensitivity to the NMR signal for the RF coils. The Bi field magnitude is selected within a specific range, which corresponds to the region where a RF pulse causing a 180- degree excitation for the Bo bandwidth is possible. For these simulations, Bi magnitudes between 1.5-6 microtesla was chosen as the "detectable" region, shaded in grey in the slices shown in Figures 8(c) and 8(d).

[0110] The Bi detectable region maps a series of sectors across the bore volume, aligned with the RF coils. The angular size of the sector was controlled by the width of the RF coil, while the Bi decay with distance from the RF coil was also dependent on the width and dimensions of the RF coil.

[0111] In one embodiment, the coil array was configured as a plurality of RF coils that both transmitted and received RF pulses in the bore volume. In this configuration, pulses from each RF coil excited a sector of the bore, as the Bi field it produced was inhomogeneous. The plurality of RF coils were used to detect the signal from the excited sector. In this embodiment, this arrangement was found to provide good spatial resolution, as the Bi inhomogeneity controlled both the excited region and the detected region.

[0112] In another embodiment, the coil array was configured as an array of RF receive-only coils with a separate volume transmit coil. The transmit coil was configured to excite the whole acquisition band in one experiment, essentially exciting a ring. The array of receive coils still provides spatial information due to the Bi inhomogeneity of each receive coil to different sectors. This provided the benefit of faster acquisition over the target region, as it did not require the NMR measurements to be repeated for each individual coil and frequency combination. It also reduced the requirement for high power switching between the different coils. The transmit coil can follow designs used in conventional MRI and NMR systems, such as the birdcage or saddle coil designs, which produce transverse Bi over a volume. It is envisaged that for a real-world application, the power and / or duration of the RF pulses through the Bi RF coils will need to vary depending on the intended region within the bore. Furthermore, the sensitivity across the detectable region will also vary depending on distance from the RF coil.

[0113] Example 3 -Acquisition Method, Identification of Target Region and Coverage

[0114] The coverage of the device is dependent on the spatial distribution of the Bo and B2fields, so it is desirable to ensure that target regions for the particular indication are inside the coverage region and within the volume of the bore. The inhomogeneous Bo and B2fields preclude the use of conventional MRI imaging techniques and pulse sequences for obtaining and localising NMR signals across the bore. Conventional NMR experiments would only detect signals from a small region of the bore and would not provide coverage of the target regions.

[0115] To address this, a method for Magnetic Resonance Imaging in static gradient was introduced. The inhomogeneous Bo field was split into a series of bands with different magnetic field strengths along the gradient and this resulted in a series of resonant frequencies. The different bands reflect different radial depths inside the bore. The thickness of these bands in space was determined by the bandwidth of the RF excitation pulses produced by the spectrometer. A series of NMR measurements with the excitation frequency set to the resonant frequency of each individual band were made, which obtained signals from each band. Combining the results from the different bands increased the coverage across the bore.

[0116] Further spatial localisation is given by the RF coil array. As described above in Example 2, each coil has a sensitivity pattern, due to the inhomogeneous Bi field it produces. Making a series of measurements using the different RF coils in the array allowed the signals to be localised to the specific sector of the bore.

[0117] The spatial localisation technique may be combined with a range of pulse sequences to enable conventional MRI contrasts to be obtained. This includes Tl-weighted, T2-weighted and Diffusion- weighted imaging. Measurements from the different coil and band combinations allow the intensity of signals from different locations inside the body part to be compared, providing information about the position and size of potential lesions.

[0118] To simulate the coverage of the spatial localisation technique, the simulated Bo magnetic field image for the magnet described below in Example 6 was used for a coverage study. The Bo field image was sliced into a series of 16 frequency bands, defined by a series of centre frequencies (ranging from 4.1-4.9 MHz) and an excitation bandwidth for each band (assumed to be 50 kHz). The bandwidth and number of bands were chosen to match with the limits of the spectrometer hardware, which has a limited range of frequencies it can tune and acquire signals on. Each simulated acquisition band reflected the volume within the magnetic field that is excited at a specific B2frequency and bandwidth, and by combining the volume of the bands with different excitation frequencies, the overall coverage of the system was obtained. It is envisaged that in real-world application, the number, frequencies, and bandwidth of the acquisition bands will be set based on the limits of the specific spectrometer and RF acquisition hardware, as well as the specific field strength and gradient generated by the magnet array in each band, and the desired resolution.

[0119] As the coverage region and resolution produced by the spatial localisation technique is different to conventional MRI images, it was important to design the magnet array and RF coil array so that the Bo and B2fields of the device allowed coverage of the most important regions of the body part for specific disorders. Whilst the device could be used for a number of indication or disorders, ischemic strokes are a particular area of interest, and the inventors undertook a research exercise looking at ischemic strokes to identify target regions. By way of background, ischemic strokes are caused by blockages in the vasculature, so are statistically more likely to occur in some locations than some others due to vascular anatomy (see Bonkhoff et al). In contrast, some regions might be at lower risk to ischemia. A statistical heatmap was generated using images from a stroke neuroimaging study (Titan Neuroscience, Australia.) Patient images were normalised to the standard MNI space and the stroke lesions segmented to show regions of the brain affected by stroke. Combining the lesions and averaging across all patients yielded a statistical heat map shown in Figure 9 (a) - shown in the XY plane and 9 (b) - shown in the XZ plane that shows regions of the brain that are most likely to be affected by stroke. The values in the 3D image correspond to probability of the voxel being affected by stroke in the patients in the dataset.

[0120] The heat map showed that ischemic strokes are most common in the middle cerebral artery (MCA) region, which meant that other lesion types were not well represented in the final heat map. To address this issue, weighting of clinically significant types of stroke was increased, which artificially added more heat to stroke-affected regions outside of the MCA region, and proportionally reducing the heat in the remainder of the brain. This additional weighting produced a second heat map which was used for the optimisation and design of the system - see the heat maps 9(c) - shown in the XY plane and 9(d) - shown in the XZ plane.

[0121] The heat maps were thresholded to identify voxels that had a significant probability of containing a stroke lesion. Voxels above the threshold were combined to define the target region. This process allowed the target regions for ischemic stroke to be identified and quantified within the bore volume, although this approach may be applied with other conditions. To assess the potential performance of the NMR device, the above target regions and the frequency bands were combined. The acquisition bands were overlaid with the target region with a matching grid and the number of target region voxels inside the acquisition bands counted. This produced a geometric coverage score that could be used to inform the design and optimisation of the magnet array.

[0122] As an example of this method, planes from coverage score calculation for the magnet described in Example 6 are shown in Figure 10. Figure 10 (a) shows an XY plane through the centre of the magnet array (z = 0 mm) with contours indicating the frequency bands. The plane of the aligned and overlaid target region from the weighted heatmap described above is shown in Figure 10 (b), indicating that the whole target region in this slice was inside the acquisition band. A second XY plane from lower down in the bore (z = -32 mm) is shown in Figure 10 (c) and (d), showing the target region and coverage. The result of this process was a coverage score, which for the weighted heatmap and magnet array was 88%. The coverage score for the magnet array and unweighted heatmap is 93%. These coverage scores provided confidence that the Bo field distribution produced by the magnet array has the potential to detect signals from the majority of regions where strokes occur.

[0123] Example 4 - Measurement simulation using data from stroke patients use diffusion weighted imaging

[0124] One goal of the device is to provide a way to rapidly diagnose whether or not a subject has been affected by a stroke. To understand the sensitivity of the NMR device to stroke, we simulated the signals the device acquired in a set of individual MRI images of stroke patients using the Australian TITAN Neuroscience stroke imaging database. The results obtained provided a guide to the potential performance of the device, based on actual and real stroke data.

[0125] The simulation was achieved by using diffusion weighted imaging (DWI). DWI contrast is very sensitive to microstructural changes in ischemic stroke and it is often used clinically to diagnose a stroke. The decrease in diffusion during stroke creates a lesion of increased signal intensity in the MRI image. The device design selected for use in this example was as described below in Example 6.

[0126] To simulate the signals acquired by the system and estimate signal patterns of different injuries, the Bo and B2field maps were combined to create a series of 3D acquisition bands. Each combination of coil and Bo band produces what we have termed an "acquisition band". The acquisition bands were overlaid and aligned with existing 3D MRI imaging data for individual subjects. The summed intensity of MRI image voxels inside each acquisition band gave a simulated signal for measurements in each band. While the simulation focused on DWI, other signals that could be investigated include those that would be known to someone skilled in MRI imaging, such as T2, T2 Flair, DWI and the like. An example of the series of acquisition bands is shown in Figure 11 (overlaid on the heatmap described above as an anatomical reference), with the bands for the left and right hemispheres shown in the bands in the slices in the left and right columns respectively. Further, the lower two slices show the acquisition bands corresponding to the rear left and rear right coils, which allow signals from the indicated sector of the brain to be detected.

[0127] The study began with a b=1000s / pm2diffusion-weighted image, obtained from a stroke subject and including a lesion, that was collected on a conventional clinical MRI system. The image was normalised to the standard MNI space and the brain volume extracted. The lesion within the brain was annotated manually to test the intersection with the series of acquisition bands. The bands were then intersected with the brain volume images, and the DWI intensity of voxels within each band was summed. This simulated the acquisition of a diffusion weighted signal for the device for each band.

[0128] The simulated signals were fed into a simple classifier to identify the extent and hemisphere of ischemia within the brain. By comparing the DWI signal from acquisition bands in the different hemispheres of the brain, the hemisphere with the ischemic lesion could be identified by its higher diffusion-weighted signal. The unaffected hemisphere essentially served as a control. Depending on the volume of the ischemic lesion and the change in diffusivity, the difference in signal from the two hemispheres can be used to identify ischemia.

[0129] This process was carried out over 120 stroke images and the data obtained is shown in Figure 12. Figure 12 clearly shows that the difference in DWI signal between the two hemispheres is correlated between the two hemispheres with the size of the ischemic lesion and that the device and measurement simulation is predictive of stroke detection and diagnosis.

[0130] Example 5 - Signal Localisation for Image Output

[0131] As discussed above in Example 3, the inhomogeneous Bo and B2fields produced by the device can be used to localise NMR signals obtained by the device. It is advantageous to display this in an intuitive way to clinicians, so the inventors have proposed a method for producing an image from the NMR signals it measures. The method relies on prior knowledge of the Bo and B2fields designed in Example 1 and Example 2. To produce an image in real space, the contribution of spins in each location in the bore must be known for each coil and band combination. This was found using the simulation methods described in Example 1 and 2, but may also be measured directly by mapping the fields in space with a gaussmeter, or measuring a known calibration sample. To generate the output image, the measured NMR signals for each band from each coil were processed to produce weighted values reflecting the desired signal contrast for each band from each coil. This included common MRI contrasts such as Ti-, T2- or diffusion-weighted contrast. The value for the band was used to set the image intensity for each pixel in the band. Image intensity for overlapping bands was set using the weighted average of the sensitivity map at each pixel. This produced images that are a projection through the target region, convolved with the shape of the acquisition bands as an effective point-spread-function. Further image post processing techniques common in conventional MRI may be applied to the image output to alter image contrast.

[0132] Example 6 - Construction of NMR Device

[0133] One example of the device is shown in Figure 1. It contained a magnet array designed using the method above, comprising a ring magnetised in, a ring magnetised out, and one additional ring in the centre. It stretched l.lx along the y-axis, and the rings were curved to follow the plane of the target region. It produced a 96-115 mT field in the brain volume. The weight was approximately 30 kg, including a mild steel yoke. It had adequate clearance for the 99th percentile largest adult head. It was combined with 12 RF coils in an array, where the coils were equally spaced around the head.

[0134] Each ring was constructed using 18 magnet blocks, preferably 1.5 tesla (T) neodymium iron boron (NIB) - grade N 42, with blocks 35mm x 35mm x 50mm in dimension. The blocks were magnetised along the 35 mm axis with a 1.3 T remanence field. Sourced from Shanghai Jin Magnet. The yoke pieces were machined from 8 mm thick plates of mild steel having a length dimension of 300 mm x 35 mm. Mild steel was chosen to have a high magnetic permeability, to concentrate the magnetic field inside the array. The magnets and yokes were attached to an aluminium frame using stainless steel fasteners. The radio frequency coils were formed from several turns of enamelled copper wire having a diameter of about 150 mm. The magnet array was housed within a plastics shell (not shown in the Figure) and the RF coils were located on the inside of the shell, close to the bore and body part to be measured. The final weight of this magnet array was about 32 kgs, more preferably less than about 25 kgs.

[0135] Advantages

[0136] The NMR device provides a number of advantages over existing technologies because of the integrated design of the magnet array, RF coil array, NMR acquisition method and application. Conventional systems for NMR and MRI rely on a strong >1.5 T and homogeneous Bo field. In contrast, the present device does not require a homogeneous field, instead using an inhomogeneous field which is designed to provide coverage and localisation across the brain volume. The magnet array to produce the inhomogeneous Bo field is significantly simpler and lighter than the magnets used to produce the Bo field in conventional systems. It also more inexpensive, because the magnetic field is designed to be mostly in the target region, requiring less magnetic material in the array.

[0137] The low magnetic field (<120 mT) the device produces is lower risk and safer to use than the strong fields used in conventional MRI systems (>1.5 T). The lower field produces less force on nearby ferromagnetic objects. The magnet design with yokes also reduces the stray magnetic field outside of the device. Furthermore, at this field strength, the B2excitation frequency is lower, producing less RF power deposition and heating in the body part.

[0138] The static gradient technique means that additional hardware such as gradient coils and amplifiers used in conventional scanners are also not required. This reduces the power required to run the system, enabling it to be powered from portable batteries or a plug in power source. This enables the device to be made significantly smaller, lighter and portable.

[0139] An inexpensive, lightweight, quiet in operation and portable device enables new applications for example in ambulances or in remote areas. For the specific indication of ischemic stroke, a portable device to diagnose stroke could improve patient outcomes by speeding up the pathway to diagnosis.

[0140] While the apparatus and methods of this disclosure have been described in terms of the embodiments included herein, it will be apparent to those of ordinary skill in the art that variations may be applied to features or integers of the apparatus and / or methods described herein without departing from the concept, spirit, and scope of the disclosure. All such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the scope, and concept of the disclosure as defined by the appended claims.

[0141] References

[0142] Anna K. Bonkhoff, Tianbo Xu, Amy Nelson, Robert Gray, Ashwani Jha, Jorge Cardoso, Sebastien Ourselin, Geraint Rees, Hans Rolf Jager, Parashkev Nachev, Reclassifying stroke lesion anatomy, Cortex, Volume 145, 2021,

[0143] D.J. Griffiths (2007). Introduction to Electrodynamics (3rd ed.). Pearson Education, p. 276. ISBN 978- 81-7758-293-2.

Claims

CLAIMS1. A nuclear magnetic resonance (NMR) device, suitable for measurement of NMR signals within a target region of a body part of a subject, including:(a) a plurality of magnets arranged in an array, the magnet array being configured to receive the body part of the subject; the magnet array being configured to create a first inhomogeneous magnetic field (Bo) having a Bo static field gradient within the body part of the subject under examination; wherein the magnet array comprises a plurality of spaced apart magnet rings, each ring configured to extend about the body part;(b) a plurality of radio frequency coils arranged in an array and configured between the magnet array and about the body part of the subject, in use, each coil configured to create an individual inhomogeneous magnetic field (B ) substantially perpendicular to the first inhomogeneous magnetic field (Bo), the plurality of radio frequency coils configured to create a plurality of different radio frequencies and bandwidths across the volume of the body part of the subject; and(c) acquisition means to acquire NMR signal data from the different bandwidths within the Boand Bi gradients and to process the magnetic resonance signal data to provide spatial localisation across the volume of the body part;(d) wherein the configuration of the magnet array and the radio frequency coil array is such to ensure that the Bo and Bi fields provide coverage over substantially all the volume of target region within the body part within the device.

2. The device as claimed in claim 1, wherein the magnet array comprises a plurality of spaced apart yokes, each yoke supporting at least a pair of spaced apart magnets, the yokes and magnets being arranged in an array whereby the magnets define a ring that defines a bore within the device.

3. The device as claimed in claim 2 wherein the spaced apart yokes are linear and each support at least a pair of magnets.

4. The device as claimed in claim 2, wherein the spaced apart yokes are substantially curved around the magnet array to form the magnet ring.

5. The device as claimed in any one of claims 1 to 4, having three or more magnet rings.

6. The device as claimed in any one of claims 1 to 5 wherein the radio frequency coil array comprises a plurality of coils configured into an arrangement to extend between the magnet array and about the body part, the radio frequency coil array being configured to provide spatial information across the volume of the target region.

7. The device as claimed in claim 6, wherein each radio frequency coil is sensitive to spins within a particular sector of the bore.

8. The device as claimed in claim 6, wherein the radio frequency coil array is configured to provide a transmit-only coil, and a plurality of receive-only coils.

9. The device as claimed in claim 6, wherein the radio frequency coil array is configured to provide a plurality of radio frequency coils that can transmit and receive.

10. The device as claimed in claim 6, wherein the plurality of radio frequency coils are configured to transmit simultaneously.

11. The device as claimed in claim 6, wherein the plurality of radio frequency coils are configured to receive simultaneously.

12. The device as claimed in any preceding claim wherein the cross section of the bore defined by the magnet rings is substantially elliptical.

13. The device as claimed in any preceding claim wherein the side profile of each of the magnet rings is non-planar.

14. The device as claimed in any preceding claim wherein the magnets in the array are irregularly spaced apart.

15. The device as claimed in any preceding claim wherein the magnet array is configured to provide a first controlled inhomogeneous magnetic field (BO) has a field strength of about 80 mT to about 120 mT, preferably about 100 mT, within the bore.

16. The device as claimed in any preceding claim wherein the magnet array is configured to provide a gradient of magnetic field Bo across the target region of about 15mT to about 20mT.

17. The device of claim 15, wherein the gradient of magnetic field Bo is primarily in the radial direction across the target region.

18. The device of claim 16, wherein the magnet array is configured to produce magnetic field Bo contours that are substantially straight across the target region.

19. The device as claimed in any preceding claim, wherein the device is portable.

20. The NR device as claimed in any preceding claim, wherein the portable system weighs less than about 30 kgs, preferably less than about 25 kgs.

21. The device as claimed in any preceding claim, wherein the body part is a head of the subject.

22. The device as claimed in any preceding claim, wherein the subject is a human.

23. A method for NMR data collection using a device as claimed in any one of claims 1 to 22; the method including the steps of(a) applying a controlled inhomogeneous magnetic field Bo across a volume of a target region of a body part of a subject to generate a series of acquisition bands with different resonant frequencies;(b) exciting nuclear spins within each acquisition band among a set of acquisition bands that collectively cover the target region of the body part by means of radio frequency pulse generation and transmission from one or more radio frequency coils to cause the spins to generate a plurality of unique radio frequency signals;(c) receiving the plurality of unique radio frequency signals emitted by the nuclear spins from the acquisition bands that collectively provide spatial information across the target region of the body part by using the unique spatial sensitivity of each radio frequency coil; and(d) processing the received radio frequency signals to provide data representing the magnetic resonance property(ies) of the target region.

24. The method as claimed in claim 23, wherein in step (d) the data representing the magnetic resonance property(ies) of the target region is further processed into an image.

25. The method of claim 23 or claim 24, wherein steps (a) to (d) are carried out in less than about 20 minutes.

26. The method of any one of claims 23 to 25 wherein steps (a) to (d) are carried out in less than about 15 minutes.

27. The method of any one of claims 23 to 26, wherein steps (a) to (d) are carried out in less than about 10 minutes.

28. The method of any one of claims 23 to 27, wherein independent signals are received using at least a plurality of radio frequency coils simultaneously.

29. The method of any one of claims 23 to 28, wherein in step (b) the radio frequency pulses generated have an excitation bandwidth of about 40 kHz to about 60 kHz30. The method of any one of claims 23 to 29, wherein in step (a) the series of acquisition bands generated comprises at least 5 acquisition bands.

31. The method of any one of claims 23 to 30, wherein the magnetic resonance property of the target region is diffusion.

32. The method of any one of claims 23 to 31, wherein the magnetic resonance property of the target region is perfusion.

33. The method of any one of claims 23 to 32, wherein the magnetic resonance property of the target region is T2.

34. The method as claimed in any one of claims 23 to 33, wherein the body part is a head of the subject.

35. The method as claimed in any one of claims 23 to 34, wherein the subject is a human.

36. The method as claimed in any one of claims 23 to 35, wherein the subject is in a setting remote from a hospital.

37. The method of claim 24 where the data is processed into an image in real space by combining the signal from each coil using the sensitivity map for each coil in real space.

38. The method of claim 24 where the image is presented as a projection through the target region.

39. A method of diagnosing a brain injury using a device as claimed in any one of claims 1 to 22; the method including the steps of(a) applying a controlled inhomogeneous magnetic field Bo across a volume of a head of a subject to generate a series of acquisition bands with different resonant frequencies;(b) exciting nuclear spins within each acquisition band among a set of acquisition bands that collectively cover the head by means of radio frequency pulse generation and transmission from one or more radio frequency coils to cause the spins to generate a plurality of unique radio frequency signals;(c) receiving the plurality of unique radio frequency signals emitted by the nuclear spins from the acquisition bands that collectively provide spatial information across the head by using the unique spatial sensitivity of each radio frequency coil; and(d) processing the received radio frequency signals to provide data representing the magnetic resonance property(ies) of the target region; and(e) interpreting the data to diagnose the presence or otherwise of a brain injury.

40. The method as claimed in claim 39, wherein in step (d) the data representing the magnetic resonance property(ies) of the target region is further processed into an image.

41. The method of claim 39 or claim 40, wherein steps (a) to (d) are carried out in less than about 20 minutes.

42. The method of any one of claims 39 to 41 wherein steps (a) to (d) are carried out in less than about 15 minutes.

43. The method of any one of claims 39 to 42, wherein steps (a) to (d) are carried out in less than about 10 minutes.

44. The method of any one of claims 39 to 43, wherein independent signals are received using at least a plurality of radio frequency coils simultaneously.

45. The method of any one of claims 39 to 44, wherein in step (b) the radio frequency pulses generated have an excitation bandwidth of about 40 kHz to about 60 kHz46. The method of any one of claims 39 to 45, wherein in step (a) the series of acquisition bands generated comprises at least 5 acquisition bands.

47. The method of any one of claims 39 to 46, wherein the magnetic resonance property of the head is diffusion.

48. The method of any one of claims 39 to 47 wherein the magnetic resonance property of the head is perfusion.

49. The method of any one of claims 39 to 48, wherein the magnetic resonance property of the head is T2.

50. The method as claimed in any one of claims 39 to 49, wherein the subject is a human.

51. The method as claimed in any one of claims 39 to 50, wherein the subject is in a setting remote from a hospital.

52. The method as claimed in any one of claims 39 to 51 wherein the brain injury is an ischemic stroke.

53. The method as claimed in any one of claims 39 to 52, wherein the brain injury is a haemorrhagic stroke.

54. The method as claimed in any one of claims 39 to 53, wherein the brain injury is neonatal hydrocephaly.

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