Phantom for multi-parametric calibration in magnetic resonance imaging

Abstract

A phantom for use in an MRI scanner includes an outer housing and a plurality of vessels located within the outer housing, where each of the vessels contains a material. The value of a property of the material at a particular temperature is different for each of the vessels. The phantom also includes a phase change material between the outer housing and the vessels. Also provided are a method for manufacturing a phantom, a method for obtaining calibrated measurements from non-calibrated images using a phantom, a system for obtaining calibrated measurements from non-calibrated images, and a coil assembly for use in an MRI scanner.

Claims

1. A system, comprising: a phantom for use in a magnetic resonance imaging (MRI) scanner, the phantom comprising: an outer housing; a plurality of vessels located within the outer housing, each of the vessels containing a material, wherein the value of at least one property of the material at a particular temperature is different for the material contained within each of the vessels; and a phase change material between the outer housing and the vessels, wherein the phase change material has a transition temperature or melting point close to body temperature.

2. The system of claim 1, wherein at least a part of an outward facing surface of the outer housing is a concave surface and wherein the vessels are each fixed at an equal distance from the concave surface.

3. The system of claim 1, wherein the outer housing comprises two flat side faces and the vessels extend between and are coupled to the side faces to hold the vessels in position.

4. The system of claim 1, wherein the outer housing is shaped as a cuboid.

5. The system of claim 4, wherein the outer housing has a maximum dimension of 5 cm to 25 cm, such that it can fit and be integrated within RF coils of the MRI scanner.

6. The system of claim 1, wherein the outer housing is configured to be positioned adjacent an inner surface of a head and/or neck coil of the MRI scanner.

7. The system of claim 6, wherein the outer housing is formed as a ring.

8. The system of claim 1, wherein the material within the vessels is a liquid or a polymer dissolved in water, and wherein the concentration of the polymer in solution is different for each of the vessels.

9. The system of claim 8, wherein the liquid within the vessels comprises a metallic salt dissolved in water, and the concentration of the metallic salt is different for each of the vessels and wherein the metallic salt comprises one or more of a compound with paramagnetic ions, Nickel Chloride, Copper Sulphate, Gadolinium, Manganese Chloride, and Iron Oxide.

10. The system of claim 8, wherein the liquid within the vessels comprises one or more of polyvinyl pyrrolidone, a hydrogel comprising water and polyglucan molecules, a mixture of water, and one or more organic oils.

11. The system of claim 1, wherein each of the vessels comprises a vessel inner shell and a vessel outer shell, and wherein the phase change material is contained between the vessel inner shell and the vessel outer shell of each of the vessels.

12. The system of claim 1, wherein the phase change material fills the whole of the space between the vessels and the outer housing.

13. The system of claim 1, comprising an item of clothing including an attachment device, wherein the housing is coupled to the clothing using the attachment device.

14. The system of claim 1, wherein the material within the vessels comprises an injectable MRI contrast agent, and wherein the concentration of the contrast agent in each of the vessels is different.

15. The system of claim 14, wherein the contrast agent is one or more of gadolinium-based, Nickel Chloride, Copper Sulphate, Gadolinium, Manganese Chloride, and Iron Oxide.

16. The system of claim 14, wherein the material within the vessels comprises a gelling agent, and wherein the material within the vessels comprises a compound with paramagnetic ions.

17. The system of claim 16, wherein a ratio of gelling agent to paramagnetic ions is selected such that the material within the vessels matches an intrinsic T1 to T2 ratio of tissue.

18. A method for obtaining calibrated measurements from non-calibrated images using a phantom, the method comprising: heating the phantom of claim 1 to melt the phase change material; allowing the phase change material to cool; disturbing the phase change material to begin a process of crystallisation; locating the phantom within the scanner adjacent a subject to be imaged; scanning the phantom and the subject simultaneously to produce raw image data while the crystallisation process is ongoing; deriving a correction function from values of the property measured from the raw image data of each of the vessels and known values of the property for the material within each of the vessels; and applying the correction function to the image data of the subject to produce a calibrated image.

19. The system of claim 1, further comprising a processor coupled to the phantom and to the MRI scanner, the processor configured to: receive raw image data of a subject and the phantom; derive a correction function from values of the property measured from the raw image data of each of the vessels and known values of the property for the material within each of the vessels; and apply the correction function to the image data of the subject to produce a calibrated image.

20. The system of claim 1, further comprising a coil assembly for use in the MRI scanner, the coil assembly comprising a radio frequency coil array and a housing, wherein the housing has one or more spaces between the coils and at least one of the spaces contains the phantom.

21. A method for manufacturing a phantom for use in a magnetic resonance imaging (MRI) scanner, the method comprising: filling a plurality of vessels with a material, wherein the value of a property of the material at a particular temperature is different for each of the vessels; providing an outer housing surrounding the vessels; and providing a phase change material in the volume between the vessels and the outer housing, wherein the phase change material has a transition temperature or melting point close to body temperature.

Description

(1) Embodiments of the present invention will now be described in detail with reference to the accompanying drawings, in which:

(2) FIG. 1A shows a diffusion phantom located adjacent a patient on a table prior to a scan;

(3) FIG. 1B illustrates a possible location of the phantom housing relative to the patient;

(4) FIG. 2A shows a perspective view of a diffusion phantom;

(5) FIG. 2B shows a side view of the diffusion phantom shown in FIG. 2A with vials shaded to represent the concentration of PVP in the solution within each vial;

(6) FIG. 3 shows an RF head and neck coil including integrated phantom components;

(7) FIG. 4 shows an RF coil array and housing including spaces between the coils, each configured to hold a phantom or a phantom component;

(8) FIG. 5 shows a calibration system including a phantom;

(9) FIG. 6 shows a graph of measured and expected ADC values for each of the vials in a phantom;

(10) FIG. 7 illustrates an optical temperature probe for use with the phantom or as part of the phantom;

(11) FIG. 8 illustrates a wearable vest into which housing portions containing vessels are incorporated.

(12) The calibration phantom described below is specifically designed to be imaged at the same time as a patient in the same scanner (as an in-image calibration device). Features of the device, such as the particular shape of the phantom and the proximity of the vials to the outer housing, make this easier and more comfortable for the patient, and improve accuracy of the subsequent calibration stage. This high level of accuracy is achievable using an in-image phantom because changes occurring in the imaging system before or after an image of the subject is taken will not affect the calibration process. Most phantoms are overly bulky and are shaped as a cylinder or sphere preventing them from fitting comfortably within the MRI coil along with the patient or body part to be imaged, so that it is not possible to image the phantom simultaneously with a patient. The system also provides calibration images of material having a range of carefully controlled values of a property to be measured, the range corresponding to values expected to be measured from both healthy and abnormal tissues. Providing a range of measurements for use in calibration can help to correct for non-linearity and ensure that values of the relevant property or properties are measured consistently across images taken at different times by the same scanner and across different scanners.

(13) In FIG. 1A, the phantom is located above the body as part of a torso pad and is strapped to the patient's waist to prevent movement relative to the body during scanning. The housing may be waterproof and designed to contain a phase change material which is used to keep vials 4a-k at a constant temperature during the scan, as described in more detail below. The phantom may also be located underneath the patient's torso. FIG. 1B shows a side view of the patient with the torso pad including the phantom strapped around the patient's middle. This may represent a single pad extending all of the way around the body or two separate pads, one strapped above the body and another positioned underneath the lower back of the patient (and possibly integrated into a table on which the patient can lie during a scan).

(14) An example of a phantom is shown in FIG. 2A. The phantom comprises an outer housing or container 2 which is shaped to fit the contours of a patient's body. Within the housing a plurality of vials 4a-k are located, separated from the housing and each containing an aqueous solution, wherein each solution has a different value of a measurable property, such as the apparent diffusion coefficient, T1, or T2 relaxation time (the solution in vial 4a will have a value for the relevant property that is different from that of the solution in vial 4k). The value of the property for each solution may be controlled by adapting the concentration of a particular material in solution. The material may be a polymer such as PVP, useful for providing controlled values of the ADC, or may be a metallic salt or a mixture of different metallic salts, useful for providing controlled values of the T1 or T2 relaxation time. Materials may be dissolved in water to form the solution.

(15) Instead of using chemicals and/or salts to adapt the T1 or T2 relaxation time for the solution contained within the vials, vials can be filled with a contrast agent such as a Gd-based contrast agent which may be mixed with a gel. A different concentration of the contrast agent within the gel can be used for each vial (in a similar way to the varying concentration of PVP in water for the PVP based embodiments). Once the phantom has been imaged adjacent the part of the body for which a measurement is desired, the concentration of the contrast agent within the body can be determined by comparison with images of the vials including substances having known concentration of the same chemical. The vessels in this embodiment may contain water, an injectable MRI contrast agent (such as gadolinium as mentioned above), a gelling agent, and other compounds with paramagnetic ions. Examples of gadolinium-based contrast agents which are suitable for use as a component of the material within the vessels are Magnevist® and Dotarem®. Suitable gelling agents include agar, agarose, gelatin, sodium alginate, hydroxyethylcellulose, poly-acrylic acid (carbomer and carbopol), and polyacrylamide. Suitable compounds with paramagnetic ions include nickel chloride, manganese chloride, nickel nitrate, and copper sulphate.

(16) An example solution contains between around 0.1 mM and 4.0 mM of nickel chloride, between 0.01 mM and 0.1 mM of manganese chloride, between 0.25% and 3% of one of hydroxyethylcellulose, carbomer, or polyacrylamide, and between 0.01% and 1% of Magnevist®. The remainder of the solution may be made up from water. Mixtures of hydroxyethylcellulose, carbomer, or polyacrylamide wherein the total amount is between 0.01% and 1% may also be used. The precise amounts of the components used will depend on magnetic field strength.

(17) Some concentrations of nickel chloride in solution with water within a phantom required to provide particular relaxation rates can be found in Table 1 below, which is from the paper entitled “Quantitative Magnetic Resonance Imaging Phantoms: A Review and the Need for a System Phantom” by Keenan et al. (MRM, 2018, January 79(1):48-61).

(18) TABLE-US-00001 TABLE 1 Theoretical Sphere R.sub.1 (=1/T.sub.1) Values at 3 T and Corresponding NiCl.sub.2 Concentration VIF spheres Tissue spheres Sphere R.sub.1 (s.sup.−1) [NiCl.sub.2] (mg/L) R.sub.1 (s.sup.−1) [NiCl.sub.2] (mg/L) 1 0.75 87.1 0.67 69.68 2 2.63 479.03 0.94 127.40 3 6.56 1302.09 1.33 209.03 4 11.56 2347.24 1.89 324.48 5 17.56 3601.42 2.67 487.74 6 24.56 5064.64 3.77 718.69 7 32.56 3736.68 5.33 1045.15 8 41.56 8616.16 7.54 1506.93 Note: The R.sub.1 values were chosen to mimic the range of values typically encountered in a DCE-MRI study for both the VIF and tissue compartments. To achieve these relaxation rates, the corresponding concentrations of NiCl.sub.2 are provided, assuming a water-relaxation rate of 0.33 s.sup.−1 and NiCl.sub.2 relaxivity of 0.62 (mM .Math. s).sup.−1 at 3T.

(19) The ratio of the gelling agent to paramagnetic ions is preferably selected such that the T1 to T2 ratio of the material within the vessels corresponds to that of human tissue (e.g. 300-3000 ms and 10-250 ms respectively). The vessels are maintained at a temperature near to body temperature (such as at 37° C.) by the phase change material such that an image of the vessels containing different concentrations of contrast agent can be directly compared the image of the subject. This then permits direct linearisation of the MRI signal to the concentration of the contrast agent (or calibration of the image signal using the images of the material within the vessels).

(20) Clearly, it is still important for the vials and the substances contained within to be held at a temperature that is as close to body temperature as possible for comparison with a particular body part. Phase change materials may be used in order to achieve this and the structure of the housing and vials may be identical to that used in embodiments where vials contain PVP or another water-soluble material. Determination of the concentration of a contrast agent in a body part of the patient does not require analysis of T1 or T2 relaxation time, which can result in simpler and quicker image processing.

(21) Vials are preferably held in place relative to the outer housing during use. This may be by way of one or more struts per vial which can be formed of the same material as the housing and which extend from the vial to the outer housing. Alternatively, the vials themselves may extend all the way through the phantom from one side 6 of the outer housing to the other side 8 (although they must, of course, themselves be watertight in order to ensure that the solution within the vials does not leak out). In embodiments, the outer housing 2 and vials 4 can be formed of the same material and may be formed as one piece in order to simplify the manufacturing process.

(22) The housing and/or the vials can be of a variety of different shapes and may be formed by injection moulding, vacuum forming, blow moulding, casting, machined from solid blocks, or may be formed from sections of plate glued, welded or held together with fasteners. These may be formed together as a single piece or separately. Alternatively, but less advantageously, the housing could be made from glass, which would be blown into shape. A suitable material to use to form the housing and/or vials is plastic, however if ethylene carbonate (which is a solvent) is used as the phase change material the plastic of the housing and vials will need to be chemically resistant. Plastics such as polyethylene, polypropylene, Nylon, Polyamide, Polyether ether ketone (PEEK), Polyvinylidene fluoride, and fluoropolymers are particularly useful in this case as they are not dissolved by the ethylene carbonate. Any other plastic which will not be dissolved in contact with the phase change material will also be suitable. In an embodiment, the housing and/or vials can be protected from the phase change material, for example using an internal/external layer or coating of a different material. Once the housing is formed, the phase change material may be poured in through a pluggable opening, ensuring that no contaminants are introduced.

(23) Once the vials and the outer housing are formed, these can be filled with at least the solutions and phase change material respectively through openings which are then closed off to form watertight chambers to prevent mixing of the different components. Openings may be provided with a removable closure mechanism (a plug, for example) so that the phase change material and the solutions within the vials can be replaced if necessary. This way there is some flexibility in the type of phase change material used and the concentration or make-up of the different aqueous solutions contained within the vials. In particular, it is advantageous in all cases (particularly where a phantom is intended to be imaged with the subject as an in-image phantom) to use a phase change material which has a transition temperature (or melting point) close to body temperature, so in the range between 25° C. to 45° C., preferably between 36° C. and 38° C., preferably between 36.5° C. and 37.5° C., and preferably around 37° C. This means that during crystalisation the material in the vessels and the phase change material will be maintained at around body temperature. The phantom can be comfortably held close to the body part to be imaged and the conditions within the vessels will be similar to that within the body, which can make the calibration process more accurate).

(24) The vials 4 may each contain an aqueous solution comprising PVP (polyvinyl pyrrolidone), which is a water soluble polymer, or another thickening agent. When dissolved in water the ADC of the water plus PVP/thickening agent solution (at a particular temperature and pressure) depends on the concentration of agent present. Vials can be of any shape, but are preferably cylindrical as shown in FIG. 2A. The concentration of PVP/thickening agent within the aqueous solution is different for each of the vials such that the different solutions cover a range in PVP/thickening agent concentration which is designed to mimic the range of measured ADC values in the human body at room temperature. Table 1 lists various concentrations of PVP in aqueous solution along with the associated ADC of the solution. Values are given at 36.3° C., which is the fixed point temperature of ethylene carbonate. Measured ADC values for different concentrations of PVP can be sourced from https://www.ncbi.nlm.nih.gov/pubmed/28628638, and ADC values for benign and malignant tissue values can be found at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4632135/.

(25) TABLE-US-00002 TABLE 1 PVP Conc (% w/w) ADC (μm.sup.2/ms) 0 3.05 10 2.49 20 1.88 30 1.36 40 0.90 50 0.57

(26) The vials 4 may each contain an aqueous solution comprising water combined with metallic salts such as Nickel Chloride, Copper Sulphate, Gadolinium, Manganese Chloride, and Iron Oxide. When dissolved in water, the T1 of the water plus a variable concentration of metallic salts (at a particular temperature and pressure) depends on the concentration of the salts present. Vials can be of any shape, but are preferably cylindrical as shown in FIG. 2A. The concentration of salts within the aqueous solution is different for each of the vials such that the different solutions cover a range in salt concentration which is designed to mimic the range of measured T1 values in the human body at room temperature. Table 2, which is sourced from https://ws680.nist.gov/publication/get_pdf.cfm?pub_id=919826, lists example values of the concentration of aqueous nickel chloride and associated T1 measurements at 3 T.

(27) TABLE-US-00003 TABLE 2 NiCl.sub.2 Conc (Mm) T1 (ms) 0.299 1989 0.623 1454 1.072 984.1 1.720 706 2.617 496.7 3.912 351.5 5.731 247.13 8.297 175.3 11.936 125.9 17.070 89.0 24.326 62.7 34.590 44.53 49.122 30.84 69.680 21.719

(28) FIG. 2B shows a side view of the diffusion phantom of FIG. 2A. The curved shape of the outer housing 2 is visible and the ends of the vials are shown, shaded to represent the concentration solution in the liquid contained in each of the vials. Of course, the actual appearance of the solution may not be different and the shading is used in order to illustrate the change in concentration and the fact that, in this example, concentration of PVP or thickening agent, metallic salt, or another material increases from one end of the phantom to the other as described below. The major surfaces of the phantom housing can be straight rather than curved, or the phantom can be shaped to fit to or within coils as described further below. If the phantom is designed to be used to image the torso, the shape could be made to correspond to the average curvature of the lower back of a sample of people (or a sample of a particular subset of people, such as those in a particular age range, gender, or gender and age range).

(29) The device shown in FIGS. 2A and 2B comprises 11 vials, however more or fewer vials may be provided to allow for a simpler structure, or for a more accurate calibration, for example two vials at different concentration can be provided, or more than 11 vials can be provided. Generally, the number of vials present will be in the range 3 to 15, preferably 8 to 12 in order to cover a range that is large enough to cover healthy and abnormal tissue at high enough resolution to provide accurate calibration. The vial closest to one end of the phantom may contain a solution having the lowest concentration and the vial closest to the other end of the phantom may contain a solution having the highest concentration (as shown in FIG. 2B). If this is the case, vial 4a in FIG. 2B will contain the weakest solution and vial 4k will contain the strongest solution. Vials in between will contain solutions having intermediate concentrations. Concentrations may be increased between adjacent vials by equal increments in percentage by mass concentration in the solution. Non-linear increments in concentration may also be useful in some circumstances. Logarithmic or exponential increments could be used, for example. T1, T2, and ADC decay (among others) are generally represented by an exponential decay. This means that by using logarithmic-based increments in concentration of material within the vials, a linear change in signal strength between images of the various vials can be achieved. This is more straightforward to deal with in terms of processing.

(30) For T1 calibration, for example, the vial closest to one end of the phantom may contain a solution having the lowest concentration of metallic salts and the vial closest to the other end of the phantom may contain a solution having the highest concentration of metallic salts (as shown in FIG. 2B). If this is the case, vial 4a in FIG. 2B will contain the weakest solution and vial 4k will contain the strongest solution. Vials in between will contain solutions having intermediate concentrations of salts. Concentrations may be increased between adjacent vials by equal increments, logarithmic increments, or other increments in percentage by mass concentration of salt in the solution. For ADC calibration the above will still apply, however PVP may be used as the material in solution rather than or as well as metallic salts. Additional substances, such as a preservative and trace quantities of paramagnetic metal to optimise MR relaxation properties, may be used as additives in the solution. Vials may also be spaced physically along the phantom in an equidistant manner (with an equal spacing between adjacent vials).

(31) The housing may be shaped in order to be clipped to, or to fit within, the coils of a scanner. To this end, the housing may be sized and shaped such that it can be held in place within gaps present between the coils of the scanner during use. A convenient shape for the housing in this case will be a cuboid, or a shape which is generally cuboid as shown in FIGS. 3 and 4. The structure of the coils will determine the maximum size of the housing, however in some embodiments the cuboid may have a largest dimension of between around 5 cm and around 25 cm (preferably between around 10 cm and around 12 cm). The housing may include an external attachment device (such as a clip or an adhesive strip) for fixing to the coils or a part of the scanner located near to the coils to hold it in place. The fixing mechanism may be removable to allow the phantom to be taken out of the scanner for replacement, maintenance, or in order to be able to adjust the position of the phantom within the scanner for different purposes. The phantom may also be fixed next to the coils (rather than within gaps between the coils) or fixed to a table within the scanner. Even in the case of a cuboid phantom, if the phantom is sufficiently small it can be located next to or on top of a human subject within the scanner without causing discomfort. The minimum size of the phantom will be determined by the resolution of the scanner. The phantom may be modular, as described below.

(32) FIG. 3 shows an example of a coil for extending around the head of the patient (a head or neck coil). The larger coil 10 comprises an array of smaller RF coils 12 located or fixed within a housing 14. The coil housing containing the array includes receptacles or spaces 16 sized to each fit or contain a portion of the phantom. In the example shown, each vial 4 sits within its own separate module 18, and is surrounded by phase change material. Each module is generally cuboid and is shaped for a snug fit in the spaces formed in the phantom housing 14. The spaces may form receptacles including a base to support the modules 18 or may have no base but form a tight fit with the modules 18 such that these remain in place. Some other type of removable attachment mechanism may be used to keep modules 18 in place within the spaces 16 in the housing 14. The larger housing 14 in this embodiment therefore forms the outer housing of the phantom (described above) and contains the phase change material between the outer housing 14 and the vials 4 in separate compartments near to the vials. The outer housing also contains the array of RF coils. Each vial will contain a different concentration of PVP, thickening agent, salt, or another material, as described above in relation to FIGS. 2A and 2B. Of course, more than one vial can be contained within each separate module 18 and some receptacles may be left empty depending on the desired configuration.

(33) The configuration shown in FIG. 3 allows for a great deal of flexibility in terms of which materials are used within the vials as well as the positions of the vials since the separate modules 18 can easily be removed from and placed within any of the spaces 16 available. In the figure, the cuboid housings have cut-aways at the corners which may help ensure a snug fit with the coil housing 14 and, in the embodiments shown, provides a shape which corresponds to that of the RF coil surrounding it.

(34) The same is true in the case of the spinal array shown in FIG. 4. This example is similar to the head and neck coil of FIG. 3 and includes an array 20 of smaller RF coils 22 contained within a housing 24. The housing includes spaces or receptacles 25 sized and shaped to receive smaller modules 26, which contain the vials 4 and the phase change material in the area surrounding the vials. As for the head and neck coil, the spaces may or may not include bases to support modules 26 within the larger housing 24. Each module may again include a single vial, however in the embodiment shown each module houses three separate vials containing different concentrations of the PVP, thickening agent, metallic salt, or other material. Each module may be identical, or may be configured to calibrate different measurements taken with the scanner. One module may include vials containing three solutions of PVP or thickening agent with different concentrations and another module may contain three different metallic salt solutions. Modules may contain more or fewer vials than are shown.

(35) For the head and neck coil and the spinal array, any suitable material (such as any of those described herein) can be used to form the outer housing (14;24), modules (18;26), and vials 4. A solid, rather than flexible, material for the outer housing and the modules may be more suitable in these embodiments in order to ensure that the modules remain in place relative to the outer housing during a scan. Any suitable material can be used as the phase change material and as the material within the vials.

(36) Where a coil is designed to fit around the head, neck, or head and neck of a subject, the phantom may be shaped to fit within the coil and extend around the inner surface. The phantom may extend all of the way around the head or neck of the subject or only a part of the way around, and vials may be similarly located all of the way or part of the way around the head or neck. In general, any shape for the phantom (and any location of the vials within the housing of the phantom) will be suitable provided that it can be located within the imaging volume along with the subject to be imaged.

(37) Because changes in temperature affect the diffusive properties of the liquid or solution within the vials, which may be PVP or paramagnetic metallic salt solution, it is important that the temperature of the solution during the scan is maintained constant and/or is known. To this end, a phase change material is contained within the outer housing of the phantom and surrounds the vials. Phase change materials are able to release large amounts of energy during a change of phase between a liquid and a solid such that no drop in temperature is observed. Depending on the material involved, solidification can last for several tens of minutes so that a constant temperature can be maintained for at least this length of time. The temperature may be monitored during (and/or before and after) the scan to ensure that a constant temperature has been maintained. To achieve this, one or more temperature probes may be placed next to or embedded in the phantom, either within the walls of the vials or housing, or may be positioned to extend into the vials or into the housing (such that the probes may be surrounded by the material within the vials or by the phase change material). A number of these probes may be spaced around the phantom to ensure that the temperature of the phase change material is homogeneous or may extend into or be positioned next to each of the vials to ensure that the material in each vial is also at a constant temperature, and is at the same temperature, to ensure accuracy of the calibration process.

(38) A suitable material to use as a phase change material in a diffusion phantom is thermally cycled ethylene carbonate ((CH.sub.2O).sub.2CO). This material is a transparent crystalline solid at room temperature and has a melting point of 36.3° C. so that its temperature is maintained at 36.3° C. as the material solidifies. Ethylene carbonate is therefore capable of maintaining surrounding material at a temperature similar to that of a patient's skin as it solidifies and can maintain this temperature for over 30 minutes, which is longer than the average scan time. Other phase change materials can replace ethylene carbonate in the phantom. Phase change materials which have a melting point at or around human body temperature are particularly advantageous in terms of comfort for the patient. Phase change materials with a melting point of around 37° C., between 30° C. and 40° C., more preferably between 32° C. and 38° C., or still more preferably between 35° C. and 39° C., may be used to fill the phantom or part of the phantom. An example of a phase change material with a transition temperature of 37 C is PureTemp® 37 which is described at https://www.puretemp.com/stories/puretemp-37-tds and which is commercially available. The following method used to prepare a phantom for a scan will apply to phantoms including such phase change materials as well as to phantoms containing ethylene carbonate as the phase change material.

(39) Prior to the scan, the phantom may be heated to a temperature of 40 to 50° C. in order to melt the ethylene carbonate or to at or above the melting point of whichever phase change material is used. It is important that the phase change material is fully melted so that when the crystallisation process is initiated the temperature will be homogeneous within the phantom (heating to a temperature above the melting point of the phase change material will help to achieve this). This may be achieved using a bath of warm water into which the phantom is immersed until all of the ethylene carbonate, or other phase change material, has melted. Any method capable of heating the phantom in order to melt the phase change material will be suitable and the heating mechanism may in some embodiments be integrated into the phantom itself or into the scanner. As an example, an electrically powered heating element (such as one or more resistive elements) may be coupled to the phantom on or near to the walls of the outer housing. Current can be passed through the resistive elements prior to the scan in order to heat the phantom and melt the phase change material. The component including the resistive elements may be removed prior to the scan.

(40) The phantom may also incorporate tubes or an additional housing outside of the main housing forming a volume which can be filled with fluid (such as water). This heat transfer fluid can be pumped through to heat the phase change material prior to a scan. If tubes are incorporated, these may run into and within the main housing and into the volume containing the phase change material in embodiments, or may lie outside of the main housing. This heat transfer fluid will have its own thermal control system comprising a pump and a controlled heat source, which may be one or a plurality of resistive heating elements in an embodiment.

(41) Once the ethylene carbonate, or other phase change material, has melted the phantom may be allowed to cool, at which point it will go below its freezing temperature (of 36.3° C. in the case of ethylene carbonate) and will become super-saturated. Once cooled, the phantom can be shaken in order to start the crystallisation process and the latent heat of fusion produced during crystallisation will maintain the phantom at a substantially constant temperature. The scan is then taken of the phantom along with the patient while the crystallisation process is ongoing, such that the liquid within the vials (such as PVP/thickening agent or metallic salt solution) is also kept at a substantially constant temperature. As mentioned, if ethylene carbonate is used, the process of crystallisation will last for at least the average scan time of around 30 minutes. It is not necessary for the material to be pure. For example, ethylene carbonate of 99% purity will still be capable of maintaining a constant temperature for sufficient time for a scan to be taken of the phantom and is readily commercially available. Ethylene carbonate is particularly suitable as a phase change material, however any other phase change material can be used so long as it is able to maintain a stable temperature for long enough for a scan to be completed. A possible alternative is diphenyl ether which has a melting point of around 26° C. Again, although pure diphenyl ether will produce better results, a material having lower purity can be used.

(42) The phantom can be shaken manually or can include a mechanism by which the device can be shaken automatically. A vibrating mechanism, such as a spring-loaded mechanism, may be included in the outer housing of the phantom or may be coupled to or located in the vicinity of the phantom inside the scanner, for example. The skilled person will be aware of the various mechanisms available for vibrating the phantom, or at least the ethylene carbonate therein, without requiring a person to pick the phantom up and physically shake it. Alternatively, an aerosol spray or alternative method can be used to abruptly cool a small volume of the phase change material to create a nucleation point, thus initiating the crystallisation process. A cooling mechanism, such as the spray, can be applied to the external side of the phantom housing to induce a focal point of phase change which can then propagate. One way to achieve this is to use a Ranque-Hilsch vortex tube to separate compressed air into a hot and cold stream and then to direct the jet of cold air at the phantom, either before placing the phantom into the scanner or while the phantom is in-situ.

(43) The phantom may be of a generally elongated and curved shape (as shown). FIG. 2A shows an example of a phantom which is shaped as a curved mat with rounded ends and flat sides. The elongated structure shown in FIG. 2A is easy to produce and is capable of holding the liquid-containing vials close to the body. Ideally, vials which are to be imaged should be as close to the part of the body to be scanned as possible to maximise the accuracy of the calibration. The elongated and curved shape of the phantom enables each vial to be held at an equal distance from, and close to, the body of the patient. The sides do not necessarily need to be flat, although flat sides (6; 8) provide a convenient surface for attachment or location of the ends of the vials 4. If plugs or the like are provided for filling and refilling the vials then the flat surface of the end of the vials in this embodiment is a convenient place to position these.

(44) The particular shape used for the outer housing may depend on the body part which is being imaged and which is adjacent to the phantom during the scan if it is to be located next to or touching the subject within the scanner. In some cases, it is preferable that the phantom is located within the scanner as close to the body part to be imaged as possible. For example, the phantom may be shaped as a hollow semi-circle in order to fit over a patient's head if the MRI scanner is being used to image a patient's brain. Such a shape would also allow the phantom to be directly included in a head coil or a head-and-neck coil, as explained in more detail above. The phantom can also be shaped to fit around the patient's torso, underneath the pelvic area, or underneath various joints of the body (knees, shoulders, ankles etc) for imaging the liver, prostate, and for musculoskeletal applications such as the imaging of joints for inflammatory processes.

(45) Many other applications are also possible and the phantom can be shaped to fit close to any part of the body fairly easily. This can be done either by forming the outer housing of the phantom to fit the shape of a particular body part initially, or to fit the average shape of a particular body part for a number of users (possibly separated by age group or gender), or by forming the outer housing to be flexible enough to conform to any shape. A suitable material to use for the production of a flexible housing is a fluoropolymer elastomer such as FKM or FPM (fluoro rubber). Alternatively, a thin fluoropolymer, such as PTFE or PVDF could be formed into a pouch. Such a flexible polytetrafluoroethylene (PTFE) or polyvinylidene fluoride (PVDF) pouch could also be formed to include an integral filling port formed from solid PTFE or PVDF. The pouch could then be easily filled with the phase change material (such as ethylene carbonate) under a vacuum to prevent the appearance of air bubbles before closing the port.

(46) In an embodiment using a flexible housing, the housing can be formed as a flexible sheet which the patient can lie on or place on top of the body or can even be formed in the shape of an item of clothing such as a hat or vest to ensure that the vials are kept as close to the part of the body to be imaged as possible. Any body part can be imaged in this way with the phantom conforming to the skin closest to the relevant body part. A phantom with flexible housing in the shape of a sheet can generally be placed close to any body part prior during a scan. The vials holding the PVP or other water soluble polymers can also be formed of a flexible material such as PTFE, PVDF, or other plastics. Among others, neoprene-based materials used to form the flexible housing provide particular advantages in that they can help to maintain the phantoms as close to body temperature and as close as possible to the patient's skin, but other type of materials can be used too. Neoprene provides a certain level of insulation, which can help to reduce any heat loss during a scan. The material is also somewhat cushioned, which will increase the comfort of the patient and allows the phantom (and the vials within) to be held close to the patient's body during the scan. The flexibility of the material allows the phantom to conform more closely to the patient's body but may make the relative positions of the vials more difficult to determine.

(47) It may be useful in such a case to incorporate fiducial markers on or adjacent the vials which can be identified in the images in order to fix the positions of the different vials for processing. These may be formed from ink, for example, on the outer or inner surface of the housing of each of the vials. Several markers may be present for each vial in order to track the shape of the vial within the image in a case where a flexible vial housing is employed. Although fiducial markers are described with reference to the flexible housing and may be particularly useful in such an embodiment, these may be used in any phantom, including those employing solid material for the vials and/or outer housing.

(48) In embodiments, a mat incorporating the phantom may be placed on a sliding table such as that shown in FIG. 1A and a patient may be positioned to lie on the mat above the phantom. The phantom could be curved as described above in order to fit comfortably around the base of a patient's back. Comfort is crucial given the long scan times required for diffusion weighted imaging, so that the particular shape of the phantom is particularly important when this type of imaging is used. In embodiments, the phantom may even replace parts of the table on which the subject will lie during the scan. Again, a curved shape could be provided in order to fit the contours of the body (for example the back). The outer housing of the phantom may be formed using a mould taken of a part of the human body to ensure a close fit.

(49) In FIG. 1A, a torso pad is used in order to ensure that the patient does not move too much during the scan. The phantom may, in embodiments, be integrated into this torso pad as shown so that it is strapped onto the patient along with the pad without any additional effort being required on the part of the radiologist administering the scan.

(50) The phantom may also take the place of a cushion placed or fixed inside the scanner. In embodiments, the outer housing of the phantom may be pliable to some extent such that it can mould to the contours of a patient (such as by using the flexible outer housing described above). The phase change material may entirely fill the volume (volume 9 in FIG. 2A) between the vials and the outer housing, or may fill only a part of this volume. In an example, the phase change material fills only an area within the phantom and close to the vials. Each vial can include an outer and inner shell, with the solution contained within the inner shell and the volume between the inner and outer shell being filled with the phase change material. Less of the phase change material is required in such a configuration which may be cheaper overall. In this case the volume between the outer shell of the vial and the outer housing of the phantom may be filled with some type of gel which, if included together with a pliable outer housing, ensures that the phantom is comfortable for a patient to sit or lay on because the phantom will conform, at least to some extent, to the body shape of the patient. Alternatively, the outer housing could be over-moulded with a foam (such as a polyurethane foam) or rubber (such as polyurethane or silicone) in order to provide an outer surface to the phantom which is able to conform at least partly to the body part of the patient being scanned.

(51) The phantom may incorporate a thermometer (such as a fiber optic thermometer) in order to track the temperature of the phantom, and in particular of the solutions within the vials. This will help to ensure that the temperature has indeed remained constant throughout the scan. If this is found not to be the case, some correction may be applied to the value of the measured property to account for this change in temperature over the scan time.

(52) The phantom can form part of a system for use in a scanner. An example of a system including a phantom is shown in FIG. 5. The phantom 28 can be located within a scanner 30, as shown, during image acquisition. Image data from the scanner which will include data relating to the phantom and data relating to the patient is passed to the processor 32 along connection 34. Any other data relating to the status of the phantom, such as temperature data if a thermometer is present, or data relating to crystallisation state of the phase change material, is passed to the processor 32 along connection 36. To this end, the phantom could include an electronics measurement unit. The unit may be located outside of the imaging volume and data sent from the phantom via wireless connection, such as via Bluetooth. Fibre optic cables or regular wires adapted for MR compatibility could be used to transfer data. The processor 32 uses the image data of the phantom and the patient in order to output a properly calibrated image of the patient, or a properly calibrated measurement of a particular property of the imaged body part. Each of the connections in the system may be wireless or wired. The system also comprises a display device 38 for receiving processed/corrected image data via connection 40 and displaying this in a visual format to the user. Storage media 42 can be used to store raw and processed image data, measurements taken using the thermometer, and/or calibration information (such as the form of the inverse function applied to the image data as the correction; see below), which can be passed to storage medium via wired or wireless connection 44 from the processor.

(53) In order to calibrate a diffusion image, a patient sits or lays inside the scanner adjacent the phantom. At this stage, the phantom has been heated, cooled, and then shaken such that the crystallisation process is occurring in the phase change material and the vials therein are being kept at a substantially constant temperature. A minimum of two diffusion weighted images of the patient and the phantom together is taken using the scanner. The ADC is calculated as the rate of change between both diffusion-weighted images acquired with different diffusion-weightings. Each vial will appear on the ADC image and the signal strength will be different for each of the vials since these contain aqueous solutions comprising different concentrations of PVP or thickening agent. A calibration relation (for example a calibration curve) can be produced from the ADC values measured for each of the vials by quantifying the difference between the measured and expected values and this curve can be used to correct measured ADC values in the image of the subject. The expected value is that which would be expected to be measured if the scanner were properly calibrated, since the actual ADC values for the solutions within the vials is known (based on the ADC value of that particular concentration of solution at the temperature of the phase change material during the scan). A similar process will be followed for other imaging methods, which may require the use of different types of solution within the vials, and may not require that more than one image be taken. Other materials which change the apparent diffusion coefficient of a material could be used as well as, or in place of, the PVP. Two main categories of material are possible examples (among others). The first includes additives to water (or another liquid) which modify the ADC, such as PVP or glycerol and the second includes material having a microscopic structure resulting in a change in the ADC. Hydrogels can also be used. A suitable hydrogel for use as the material within the vials (in particular to calibrate diffusion measurements) would be a mixture of water and polyglucan or polyglucans as described above. The concentration of polyglucan in solution could then be varied in order to set the apparent diffusion coefficient. Equal, logarithmic, or other increments in the percentage concentration of polyglucans in solution can be used, as above.

(54) FIG. 6 shows a graph plotting ADC values for each of 11 vials containing different concentration solutions of PVP or thickening agent and water. Points show measured values versus known values for each vial. In a perfectly calibrated scanner, these would all lie on the black line shown on the graph (measured=expected). In the example shown, some of the points lie away from the line by an amount greater than the uncertainty in the measurement. A mathematical fit to the set of points can be calculated and an inverse of this function applied to the image data in order to correct for inaccuracies. This process results in a calibrated image of the subject.

(55) The calibration process can also be used to monitor the performance of a scanner year on year since the difference between the measured and expected values of a particular property and the extent and form of the correction which needs to be applied to the image may change over time as the scanner ages or due to specific events. Images and information about the corrections applied each time an image is taken can be sent to storage media and kept for analysis at a later date. Data can be analysed automatically each time an image is taken or can be analysed periodically and an indicator can be provided to alert a user if anomalous results are seen or if the level correction required exceeds a certain threshold, indicating that the scanner's performance has degraded to an unacceptable level. For example, if the sum of the difference between measured and expected values exceeds a predetermined threshold value then an audible or visual signal can be provided.

(56) For each image taken using the scanner, an image of the phantom is taken along with the image of the patient. The above calibration process can be applied either as part of the post processing or during the scan. Because the data used for correction is taken at the same time as the image data itself, because the solution within the vials is kept at an extremely stable temperature by the crystallisation process occurring in the phase change material, and because a number of the vials providing a range of measurements for calibration are located within the scanner as close as possible to the body part to be imaged (due to the contoured shape of the outer housing and the proximity of the vials to the surface of the phantom), the calibration process is very accurate. In the case of DWI, a controlled ADC is achieved which covers a range of values including those representing healthy tissue and severe tumours.

(57) Instead of, or as well as, using a phase change material to maintain the vials at a particular temperature accurate measurements of the temperature of the phantom or of each of the vials can be taken using temperature sensitive sensors. These may comprise optical sensors located within capsules inside or adjacent each of the vials. In an embodiment, a temperature probe insert can be used to monitor temperature before and/or during a scan. Optical sensors are particularly advantageous in the context of MRI scanners because they will not be effected by the strong magnetic fields present inside the scanner during imaging.

(58) FIG. 7 illustrates a temperature probe comprising a fibre optic cable 46 which sits within a tube 48 (a rigid nylon tube could be used, for example). The tube protects the temperature sensor from being damaged or bent, which may hinder the transport of light along the tube. The fibre optic cable may be potted inside the tube with resin or a similar substance which can provide further protection against unwanted movement of or damage to the cable. Flexible tubing could also be used to protect the optical sensor. In general, the sensor works by delivering light via optical fibre to a material at the end of the fibre, whose optical properties are temperature dependent. This is typically either a thermo-sensitive phorphorescent sensor, or a Gallium Arsenide crystal that has a thermo-sensitive characteristic spectral edge between absorbed and reflected light. The tube is inserted through the wall of the phantom and a gland fixing nut 50 and gland sealing nut 52 help to provide a seal to prevent leakage of the phase change material. The cable and fibre pass through a tube seal 54 partly formed of a screw which passes through a hole formed in the wall of the phantom. The fixing nut 50 is coupled to the screw on one side of the wall of the phantom and the gland sealing nut 52, in some embodiments along with a gland sealing washer 55, are coupled to the screw on the other side (such as the outside) of the phantom wall 56. The gland fixing nut and sealing nut are turned such that they move towards each other along the screw until an effective seal is formed around the hole to prevent leakage from the body of the phantom.

(59) The optic fibre within the tube passes from a fibre optic thermometer coupled to one end for receiving signals in the form of light from the fibre optic cable through the phantom and past portions of the phantom for which it is desired to monitor the temperature. Since it is of particular importance to monitor the temperature at or near to the vials, the fibre optic cable may pass around or past each of the vials in turn, or may even pass through the vials with a similar sealing system as is used at the phantom wall to prevent leakage of fluid into and out of the vessels. The fibre optic cable may pass through the phantom wall twice, once to enter the housing and one to exit.

(60) In an embodiment, vessels within their housing may be incorporated into an item of clothing. An example is shown in FIG. 8 which illustrates a vest including a number of pockets in which phantoms can be placed. The housing portion may be sized to correspond to one or more pockets sewn into the vest. The housing shown in the figure is of the solid type described above and includes three vessels with different concentrations of material in each. A vest 58 is formed as shown including a number of pockets. Each of these is adapted to hold a separate housing (such as housing 60 shown in the figure) containing one or more vessels 62. The housing portions may be permanently sewn into the vest or may be removable so that housings can be placed in pockets only near to the area to be imaged prior to a scan. Pockets may be sized to correspond to the size and shape of the housing, may be larger than the housing, or may be sized to contain several separate housings in one pocket. This may make the vest more comfortable for the wearer and means that the vest is adaptable to different situations.

(61) Housings containing a different number of vessels with different solutions therein can also be easily substituted for one another in order to tailor the vest to a particular situation. The same principle of a wearable item including pockets can be adapted to any type of item of clothing, such as trousers, or a hat, for example. Each pocket will be adapted to hold (either permanently or temporarily) one or more housing portions containing phase change material and one or more vessels. In place of pockets, attachment means of any type may be used to fix the housing portions (again either temporarily or permanently) to the item such that when the item is worn the housing or housings will be located near to the area of the body to be imaged and will be held near to this body part to some extent. Fastenings on the item of clothing, such as plastic zips, buttons, or ties may be used to ensure that the item of clothing does not move too much during a scan and that the phantom housings are held as close to the wearer's body as possible.

(62) Embodiments of the present invention have been described with particular reference to the examples illustrated. However, it will be appreciated that variations and modifications may be made to the examples described within the scope of the present invention.