Phantom for use with mr imaging device

Abstract

A phantom for use with an MR imaging device, such as a clinical or pre-clinical MR imaging device, the phantom includes: a sealable tube sized to fit within the imaging device; at least one fiber bundle removably inserted within the sealable tube, each of the at least one fiber bundles comprising a plurality of fibers; and a matrix material contained within the sealable tube and surrounding the at least one fiber bundle inside the sealable tube, the matrix material being an aqueous fluid and mimicking biological tissue or fluid properties. One or more characteristics of the at least one fiber bundle and / or the matrix material are selected to evaluate imaging characteristics of the MR imaging device and / or to conduct an imaging study.

Description

TITLE: PHANTOM FOR USE WITH MR IMAGING DEVICECROSS-REFERENCE TO RELATED PATENT APPLICATION

[0001] This application claims the benefit of United States Provisional Patent Application No. 63 / 688,126 filed August 28, 2024; the entire contents of United States Provisional Patent Application No. 63 / 688,126 is hereby incorporated herein in its entirety.FIELD

[0002] The various embodiments described herein generally relate to medical imaging. More specifically, the various embodiments relate to medical imaging phantoms and methods for preparing medical imaging phantoms.INTRODUCTION

[0003] In the field of medicine, diagnostic medical imaging and medical devices have significant utility. Diagnostic medical imaging procedures such as Magnetic Resonance Imaging (MR or MRI) devices are used to diagnose certain disease states and conditions and locate pathologies. Pre-clinical imaging devices can also be of significant utility in advancing medical research and improving therapeutic strategies across various fields (e.g., oncology, neurology, genetics, etc.). For example, pre-clinical Nuclear Magnetic Resonance (NMR) systems are valuable tools in medical research due to their ability to provide detailed information in studies of disease states, modelling their advancement, understanding biological processes, translational medicine from animal models to human applications, drug efficacy investigations, etc. MR imaging, including NMR, MRI and ultra-high field (UHF) MR imaging, can be useful for studies and structural / morphology investigations. UHF systems refer to the magnetic strength, which can be approximately 18-20 tesla, and up to 28 tesla. With respect to oncology, for example, pre-clinical imaging devices can help with investigating cancer signatures of different cancer types, aiding in early detection, identifying biomarkers, and confirming or assessing drug efficacy. Other example applications include neurology (e.g., in characterisation of neurodegenerative diseases, demyelination, cellular atrophy, and tumour morphology), vascular imaging (e.g., morphology of healthy and diseased vessels), hepatology (e.g., assessment of diseases like metastates and fibrosis), regenerative medicine (e.g., assessment of treatment efficacy), musculoskeletal structuralimaging of disease states and injuries (e.g., cancers and atrophic conditions), placental structural / morphology imaging and investigations, etc.

[0004] Existing MRI phantoms are generally focused on simulation of physiologically relevant parameters in clinical systems, and therefore unsuitable for use with pre-clinical imaging devices, which are relatively small. In addition, many conventional phantoms are only suitable for certain types of imaging (e.g., diffusion tensor imaging). It is also common for phantoms to use natural or uncontrollable materials (e.g., wood fibers), making it difficult to repeatedly produce phantoms with identical characteristics.

[0005] Accordingly, a need exists for a phantom that can be used with both clinical and pre-clinical imaging devices, is suitable for many types of imaging, and uses controllable (i.e. , repeatable) materials.SUMMARY OF VARIOUS EMBODIMENTS

[0006] According to one broad aspect of the teachings herein, in at least one embodiment described herein there is provided a phantom for use with an MR imaging device, such as a clinical or pre-clinical MR imaging device. The phantom includes: a sealable tube sized to fit within the imaging device; at least one fiber bundle removably inserted within the sealable tube, each of the at least one fiber bundles including a plurality of fibers; and a matrix material contained within the sealable tube and surrounding the at least one fiber bundle inside the sealable tube, the matrix material being an aqueous fluid and mimicking biological tissue or fluid properties. One or more characteristics of the at least one fiber bundle and / or the matrix material are selected to evaluate imaging characteristics of the MR imaging device and / or to conduct an imaging study.

[0007] In at least one embodiment, the plurality of fibers are solid fibers, hollow fibers, or a combination of solid and hollow fibers.

[0008] In at least one embodiment, the characteristics of the MR imaging device include image resolution and / or image quality.

[0009] In at least one embodiment, each of the plurality of fibers for a given fiber bundle are of a same size and a same type.

[0010] In at least one embodiment, the plurality of fibers for a given fiber bundle are of differing sizes and / or differing types.

[0011] In at least one embodiment, the plurality of fibers for the given fiber bundle are blended together so that the given fiber bundle has a parametrized blend, or the plurality of fibers are co-located within the sealable tube.

[0012] In at least one embodiment, each fiber of the plurality of fibers comprises a plurality of filaments, and each filament of the plurality of filaments is cylindrically shaped.

[0013] In at least one embodiment, a tube axis extends from a first end of the sealable tube to a second end of the sealable tube, and the plurality of fibers are wound in the direction of the tube axis within the sealable tube.

[0014] In at least one embodiment, the plurality of fibers are wound in multiple dimensions within the sealable tube.

[0015] In at least one embodiment, the plurality of fibers are interwoven, crossing and / or touching each other.

[0016] In at least one embodiment, the matrix material includes a diffusivity modifier such that a viscosity of the matrix is adjusted to model a desired diffusivity for the phantom.

[0017] In at least one embodiment, the matrix material includes at least one additive to adjust a property of the phantom for imaging.

[0018] In at least one embodiment, the at least one additive includes a salt to adjust a relaxivity of the matrix material or an antimicrobial agent to adjust a sterility of the matrix material.

[0019] In at least one embodiment, the phantom further includes an inner housing removably inserted within the sealable tube, the inner housing being configured for holding the at least one fiber bundle within the sealable tube.

[0020] In at least one embodiment, the inner housing is a cable sheath or heatshrink tubing.

[0021] In at least one embodiment, the phantom further includes at least one spacer removably inserted within the sealable tube, the spacer being configured for filling a volumeof the sealable tube and maintaining the at least one fiber bundle in a desired area of the sealable tube when the at least one fiber bundle is inserted within the sealable tube.

[0022] In at least one embodiment, the sealable tube is a nuclear magnetic resonance (NMR) tube or a conical tube.

[0023] In at least one embodiment, at least a portion of the plurality of fibers are bicomponent fibers including island-in-the-sea fibers.

[0024] In at least one embodiment, the plurality of fibers are sized on a cellular to tissue scale of a biological tissue.

[0025] According to one broad aspect of the teachings herein, in at least one embodiment described herein there is provided a method of preparing a phantom. The method includes: weaving the plurality of fibers around a scaffold to form a first arrangement and immersing the first arrangement in water for a first time period; twisting the first arrangement to form the at least one fiber bundle and immersing the at least one fiber bundle in water or optionally, matrix formulation, for a second time period; at least partially filling the sealable tube with the matrix formulation; inserting the at least one fiber bundle into the sealable tube and optionally filling any remaining empty volume of the sealable tube with the matrix formulation; and sealing the sealable tube.

[0026] In at least one embodiment, the method further includes inserting the at least one fiber bundle into the inner housing and inserting both the fiber bundle and the inner housing into the sealable tube.

[0027] In at least one embodiment, the plurality of fibers are bicomponent fibers and the first arrangement is immersed in the water for the first time period to remove a soluble component of the plurality of fibers.

[0028] The In at least one embodiment, the method further includes a biological sample removably inserted within the sealable tube with the at least one fiber bundle.BRIEF DESCRIPTION OF THE DRAWINGS

[0029] For a better understanding of the various embodiments described herein, and to show more clearly how these various embodiments may be carried into effect, reference will be made, by way of example, to the accompanying drawings which show at least oneexample embodiment, and which are now described. The drawings are not intended to limit the scope of the teachings described herein.

[0030] FIGS. 1A-C are front views of example embodiments of a phantom in accordance with the teachings herein;

[0031] FIGS. 2A-2B are front views of example embodiments of a fiber bundle wound around an interior housing in accordance with the teachings herein;

[0032] FIGS. 3A-3D are images of an example embodiment of a method for producing the phantom of FIG. 1A; and

[0033] FIGS. 4A-4E are images of an example embodiment of a method for producing the phantom of FIG. 10.

[0034] Further aspects and features of the example embodiments described herein will appear from the following description taken together with the accompanying drawings.DETAILED DESCRIPTION OF THE EMBODIMENTS

[0035] Various embodiments in accordance with the teachings herein will be described below to provide an example of at least one embodiment of the claimed subject matter. No embodiment described herein limits any claimed subject matter. The claimed subject matter is not limited to devices or methods having all of the features of any one of the devices or methods described below or to features common to multiple or all of the devices and or methods described herein. It is possible that there may be a device or method described herein that is not an embodiment of any claimed subject matter. Any subject matter that is described herein that is not claimed in this document may be the subject matter of another protective instrument, for example, a continuing patent application, and the applicants, inventors or owners do not intend to abandon, disclaim or dedicate to the public any such subject matter by its disclosure in this document.

[0036] It will be appreciated that for simplicity and clarity of illustration, where considered appropriate, reference numerals may be repeated among the figures to indicate corresponding or analogous elements or steps. In addition, numerous specific details are set forth in order to provide a thorough understanding of the embodiments described herein. However, it will be understood by those of ordinary skill in the art that the embodimentsdescribed herein may be practiced without these specific details. In other instances, well- known methods, procedures and components have not been described in detail so as not to obscure the embodiments described herein. Also, the description is not to be considered as limiting the scope of the embodiments described herein.

[0037] It should also be noted that the terms “coupled” or “coupling” as used herein can have several different meanings depending in the context in which these terms are used. For example, the terms coupled or coupling can have a mechanical, fluidic or electrical connotation. For example, as used herein, the terms coupled or coupling can indicate that two elements or devices can be directly connected to one another or connected to one another through one or more intermediate elements or devices via an electric signal, an electrical connection, a mechanical element, a fluid or a fluid transport pathway, for example, depending on the particular context. Connected can mean, for example, having a touch point or intersection that maintains contact or overlap between elements, and can include coplacement of elements.

[0038] It should also be noted that, as used herein, the wording “and / or” is intended to represent an inclusive-or. That is, “X and / or Y” is intended to mean X or Y or both, for example. As a further example, “X, Y, and / or Z” is intended to mean X or Y or Z or any combination thereof. As another example, the phrases “A, B, C or any operable combination thereof” or “any combination of A, B and C” are meant to cover any combination of elements A, B and C that provides utility which may, for example, include A, B, C, A and B, A and C, B and C, or A, B and C.

[0039] It should be noted that terms of degree such as "substantially", "about" and "approximately" as used herein mean a reasonable amount of deviation of the modified term such that the end result is not significantly changed. These terms of degree may also be construed as including a deviation of the modified term such as, but not limited to, 1 %, 2%, 5% or 10%, if this deviation would not negate the meaning of the term it modifies.

[0040] Furthermore, the recitation of numerical ranges by endpoints herein includes all numbers and fractions subsumed within that range (e.g., 1 to 5 includes 1 , 1.5, 2, 2.75, 3, 3.90, 4, and 5). It is also to be understood that all numbers and fractions thereof are presumed to be modified by the term "about" which means a variation of up to a certainamount of the number to which reference is being made if the end result is not significantly changed, such as, but not limited to, 1%, 2%, 5% or 10%, for example.

[0041] Some elements herein may be identified by a part number, which is composed of a base number followed by an alphabetical or subscript-numerical suffix (e.g., 112a, or 112i). Multiple elements herein may be identified by part numbers that share a base number in common and that differ by their suffixes (e.g., 112i, 1122, and 112s). All elements with a common base number may be referred to collectively or generically using the base number without a suffix (e.g., 112).

[0042] Reference is now made to FIG. 1 A, which shows an example embodiment of a phantom 100. The phantom 100 may also be referred to as a metrology phantom or a resolution phantom. The phantom 100 is suitable for use with an MR imaging device. In particular, the phantom 100 may be used with both clinical and pre-clinical MR imaging devices (e.g., pre-clinical MRI and NMR devices). The phantom 100 may be used with smaller pre-clinical MR imaging devices since the phantom 100 is relatively small. In particular, the phantom 100 has components with dimensions commensurate with the cellular scale of biological tissues. A phantom with components on a cellular scale allow for a phantom that is compatible across different manufacturer systems, as well as established workflows and processes. In particular, the size of the filaments (discussed further below) are on the same scale as the width of axons. For example, the filaments may have a diameter of 2 microns, which are similar in size to myelinated axons in neural white matter. In other embodiments, the filaments may have a diameter between 1 to 10 microns, for example.

[0043] The phantom 100 includes an outer housing 104. The outer housing 104 is a sealable tube that is sized to fit within an imaging device. In other words, the outer housing104 is small enough to fit within small pre-clinical imaging devices. For example, the outer housing 104 may be an NMR tube, which is a thin glass-walled tube that is approximately 6- 7 inches long. The outer housing 104 may also be a conical or centrifuge tube, such as a Falcon® tube, made of a plastic, such as polypropylene. In some embodiments, the outer housing 104 may be a custom-made tube. The outer housing 104 extends from a first end105 to a second end 106 along an axis 107.

[0044] The outer housing 104 includes a cap 108 which may be used to seal closed the outer housing 104. Glue and / or heat shrink tubing may be used to reinforce the seal between the cap 108 and outer housing 104.

[0045] The phantom 100 includes at least one fiber bundle 112. The fiber bundle 112 is removably inserted within the outer housing 104. FIG. 1A shows a phantom with a single fiber bundle 112. In other embodiments, the phantom 112 may include two or more fiber bundles 112. If so, the two or more fiber bundles 112 may, for example, be co-located (i.e., placed near each other) within the outer housing 104.

[0046] Each fiber bundle 112 comprises a plurality of fibers. The fibers may be one or more type of synthetic fiber or polymeric material, each with a defined and precise size. Each fiber is made of a plurality of filaments. Each fiber may be a solid fiber or a hollow fiber. Each fiber bundle may be made up of all solid fibers, all hollow fibers, or a combination of both. In some embodiments, the filaments in the fibers may be cylindrical in shape to mimic white matter tracts. In other embodiments, the fibers may be trilobal or multi-lobal to create reference structures of various sizes. The filaments making up a fiber may be of various selectable dimensions or “sizes”. Fiber bundles 112 of a certain, known size range can be fabricated by selecting fibers of a single type (with a known and precise size). In other cases, a fiber bundle 112 of a certain size can be fabricated by blending a mixture of fibers of selected sizes to create a fiber bundle 112 in the desired size range. In other words, the fibers are blended together to form a fiber bundle 112 with a parametrized blend of fibers. The fibers chosen for a given fiber bundle 112 may be all of the same size and type, or of differing sizes and types. The fibers may be sized on a cellular to tissue scale of biological tissue (i.e., the fibers may be sized on the cellular scale, on the tissue scale, or on any scale in between cellular and tissue). As a non-limiting example, the fibers may be sized from about 0.5 microns to about 100 microns in diameter. In some embodiments, textile axons (taxons) and / or other materials may be co-located in the fiber bundle 112 in selected quantities.

[0047] Since synthetic fibers with precise dimensions are used, production of many phantoms with the same characteristics is possible (e.g., in the range of tens to hundreds of thousands of phantoms). In other words, the production of the phantoms is repeatable. Materials with desired parameters may be chosen in a controlled and repeatable way,ensuring precision and reliability. Construction of the phantom, therefore, is controlled. For example, a target number of fibers of a specific size may be put in a phantom, and multiple units of this phantom may be produced. The process is codifiable and there is unit-to-unit equivalency. In some embodiments, the unit-to-unit equivalency may be within the range of 1-15%, for example, depending on the materials used.

[0048] In addition, fibers may be chosen with dimensions on the size of biological materials (e.g., brain white matter axons). Imaging of the phantom 100 with such fibers produce images with properties on biologically relevant scales. Additionally, the size of the fibers used in the phantom 100 may be relatively small, allowing for images captured of the phantom 100 by an imaging device to be of a high resolution. For example, in some embodiments, the fibers may contain filaments with diameters ranging from about 0.5 to 2 microns.

[0049] In some embodiments, the fibers may be bicomponent fibers, such as Islands- in-the-Sea (INS) fibers (e.g., FIG. 1C). The INS fibers may be processed or unprocessed. These fibers are useful since they are very precise in their dimensions. Each INS fiber has a specific number of filaments of known size in each strand. For example, the embodiment of FIG. 1C has 1 ,317,600 filaments. A specific number of INS fibers can be used to create a fiber bundle 112 of a desired size, and this process can be reliably repeated. The process is repeatable since the fibers are parameterized, meaning the number of filaments in each strand is known, and the number of loops of the fiber in the bundle is controlled. Ultimately, the number of filaments contained in the finished phantom 100 is known and controllable. Different embodiments may include INS fibers of different sizes (i.e. , with insoluble filaments of different dimensions). The INS fibers may either be made separately, or fabricated together so that a fiber contains a known quantity of at least 2 different INS fiber types. In some embodiments, the fiber bundle 112 may contain a combination of an INS fiber with a fiber with a functional lumen, or electrospun fiber of known dimension.

[0050] In some embodiments, the phantom 100 may comprise a fiber bundle 112 as well as a biological sample tissue removably inserted within the outer housing 104. The biological sample may include, for example, a sample of a neural tissue from a mouse with a neurodegenerative disease, a sample of ex-vivo tumour tissue, a control sample of healthytissue under study, etc. In other words, a fiber bundle 112 of known dimension may be imaged along with the biological sample in order to better characterize the biological sample.

[0051] The outer housing 104 may optionally contain an inner housing 114 (see, e.g., FIG. 1C). The inner housing 114 may be removably inserted within the outer housing 104. The inner housing 114 is configured for holding the fiber bundle(s) 112 within the outer housing 104. In some embodiments, an example of which is shown in FIG. 1C, the inner housing 114 is a cable sheath. The cable sheath surrounds and contains the fibers of fiber bundle 112. The cable sheath may help maintain a tight packing configuration of filaments within the fiber bundle 112, enabling anisotropic diffusion of a matrix material (described further below) in the hindered spaces between the filaments. The cable sheath may also support a manufacturable, scalable process for construction of phantoms 100 (e.g., by allowing for easy placement of the fiber bundle 112 into the outer housing 104). The cable sheath may also allow for co-location of smaller fibers. In other embodiments, the inner housing 114 may be a polymeric heat shrink covering the fiber bundle 112. An inner housing 114 may allow for intermediate components of the phantom 100 to be stored, further combined with other fibers, stored in the matrix material, and undergo quality control inspections.

[0052] In other embodiments, an example of which is shown in FIGS. 2A-2B, the inner housing 114 may be a polymeric scaffold around which the fibers of the fiber bundle 112 are wound. For example, the scaffold may be a plastic scaffold that is shaped to fit within the outer housing 104. The fiber bundle 112 may have fibers bound in one or more directions. In FIG. 2A, the fiber bundle 112 is wound in the direction of the tube’s long axis 107. The fiber bundle 112 may be wound in multiple directions and / or dimensions (e.g., 2, 3, 4, or more directions and / or dimensions). In the embodiment of FIG. 2B, the fiber bundle 112 is wound in two directions / dimensions (i.e., in the direction of the axis 107 and generally perpendicularly to the axis 107). In other embodiments, the fiber bundle 112 may be wound in more than 2 directions and / or dimensions (e.g., in a direction / dimension at any angle relative to axis 107). If the fiber bundle 112 is wound in two directions and / or dimensions, there may optionally be interweaving, crossing, and / or touching of the fibers. Also as shown in FIG. 2B, the fiber bundle 112 can have fiber wound in a direction perpendicular to its length. In some embodiments, a fiber may be wound around a circular post and removed to createa small fiber bundle 112, with the length of the fiber bundle 112 therefore dictated by the diameter of the post.

[0053] Additionally, in cases where only a portion of the volume inside the outer housing 104 is measured / imaged (e.g., some imaging systems only capture measurement / images of a section of the deepest volume of the NMR tube), the fiber bundle(s) 112 may be positioned to only occupy a targeted portion of the interior volume of the outer housing 104 and a spacer material may be used to position the smaller fiber bundle(s) 112 in the targeted portion (e.g., targeted volume) where targeted means the region of the tube which is imaged. The spacer material may be used to fill the remainder of the volume, to maintain the position of the fiber bundle(s) 112 in the targeted volume, and optionally also create a seal that prevents contamination, or for economic, functional, operational, manufacturing, or other reasons. In some embodiments, the spacer may be made of plastic and made to measure the remaining volume of the outer housing 104 (i.e., the volume inside the outer housing 104 that is not occupied by the fiber bundle 112) and maintain the position of the fiber bundle(s) 112. In other embodiments, the spacer may be made of wax and both seal the fiber in the outer housing 104 and create an air-proof barrier. In other embodiments, the spacer may comprise a combination of both of these examples.

[0054] The phantom 100 further includes a matrix material 118 contained within the outer housing 104. The matrix material 118 surrounds the fiber bundle(s) 112 inside the outer housing 104 and eliminates the presence of air in the product. The matrix material 118 is an aqueous fluid having a formulation that can be selected to mimic biological tissue or fluid properties (e.g., cerebrospinal fluid properties). The diffusivity of the phantom 100 can be controlled by using certain matrix formulations. The viscosity of the matrix material 118 may be varied to model different mean diffusivity values for the fluid. Examples of diffusivity / viscosity modifiers include Polyvinyl alcohol (PVA), or agar, or polyvinyl pyrrolidone (PVP). For example, the phantom 100 illustrated in FIG. 1 B includes 5 wt% PVA in water. In other embodiments, the matrix may be composed of between 2 wt% and 15 wt% PVA solution in water, or between 2wt% and 70 wt% PVP in water.

[0055] In another embodiment, the matrix material 118 may also include one or more additives to adjust one or more properties of the matrix material 118. In some embodiments,the additive may be a salt or other chemicals to adjust relaxivity characteristics of the phantom matrix. For example, the salt may be a gadolinium or manganese salt. In some embodiments, the additive may be nickel or copper, for example. The additives help to ensure that data that is obtained from the imaging of the phantom 100 better emulates values and data that would be obtained from biological samples. For example, the phantom 100 illustrated in FIG. 1 B includes a matrix formulation containing 90 micromolar manganese chloride. Additionally, or alternatively thereto, antimicrobial agents may be used as an additive to ensure sterility in the matrix formulation. The antimicrobial agent may be, for example, sodium azide, NaN3, or various azides and prepared formulations (e.g., German Plus).

[0056] When assembled, the interior volume of the outer housing 104 may be almost completely filled by the fiber bundle 112, or, in some embodiments, the fiber bundle 112 and spacer. There is, therefore, advantageously no contiguous volume of matrix material 118 where eddy currents are able to form and there is no bulk flow of matrix material 118. Eddy currents or bulk flow of matrix material 118 may cause unwanted measurement characteristics, such as false diffusion signals. In at least one embodiment, to minimize dilution of the matrix material 118, the fiber bundle 112 may be pre-soaked in the same matrix material 118 before adding it to the outer housing 104. This may avoid a significant dilutive change in concentration of the additives in the matrix material 118.

[0057] The assembled phantom 100 may be placed within a specialized piece of equipment for the imaging process, where it is held in place and suspended at the correct position (e.g., using nitrogen gas). In operation, the MR imaging device takes a cross- sectional image through the phantom 100 (i.e., through the fiber bundle(s) 112). A filament having a certain diameter will appear as a circle having this diameter in the image (e.g., a filament with a diameter of 2 microns appears as a circle with a diameter of 2 microns). The filament may also appear as an ellipse where the imaging slice by the MR imaging device is at an angle other than 90 degrees (i.e., the image and filaments are at an acute angle). In embodiments where filaments are also woven at 90 degrees to the long axis 107 of the fiber bundle 112, these will be represented as bars with width determined by the filament diameter.

[0058] The image of the phantom can be used in several ways. For example, the image can be used to evaluate the imaging device, including the image resolution and the image quality, and / or the image can be used as a control for an imaging study. In particular, the resolution achievable in imaging from the MR device can be tested and confirmed. For example, a researcher or clinician can verify that they are able to visualize a 2-micron structure in a sample if an image of a filament with a diameter of 2 microns produces a circle with a diameter of 2 microns (when the MR image is taken at an angle of 90 degrees relative to the filaments). The images of the phantom 100 may also be used to identify features in a research sample or sample under investigation by comparing the image from the phantom 100 with those of a sample. For example, a researcher may be comparing healthy white matter and diseased white matter from a subject, where one of the characteristics of the diseased state is a smaller diameter of white matter nerves / axons due to demyelination. The researcher may use the image of the phantom 100 as a key for more accurate characterization of healthy or diseased state tissue and may perhaps set criteria based on the image of the phantom 100 for evaluating tissue and classifying tissue as healthy or diseased. In other words, the phantom 100 provides an image reference that can be used to characterize a sample and quantify certain characteristics (e.g., diameter), and these characteristics may be used to categorize a tissue as diseased or not. In a trial, for example, the phantom 100 may allow for the determination of whether a candidate drug was efficacious and slowed or halted the progress of a disease and to what extent. The phantom 100 may be used to determine the relative efficacy of a number of candidate drugs (i.e., the drugs may be ranked against each other in terms of efficacy). In addition, the phantom 100 may be used for characterization and / or quantification of imaging biomarkers of disease and / or injury (e.g., fractional anisotropy (FA) changes and / or radial diffusivity (RD) changes). Disease and / or injury may include, for example, diffuse axonal injury as a result of traumatic brain injury (TBI) or blast-induced neurotrauma.

[0059] FIGS. 3A-3D and 4A-4E illustrate example methods for preparing a phantom 100. These methods allow for the selection of every parameter that is desired within the phantom including number of filaments, size of filaments, fiber bundle length, the matrix formulation and its properties. The methods also allow for the removal of air to prevent imaging artefacts and codify the process so that unit-to-unit equivalency is possible andmaintained. The method illustrated in FIGS. 3A-3D shows the preparation of a phantom 100 without an inner housing 114, while the method illustrated in FIGS. 4A-E shows the preparation of a phantom 100 with an inner housing 114.

[0060] The methods may both include measuring the length of the outer housing 104 to determine the needed length of the fiber bundle 112. A first arrangement of the fibers may then be prepared by weaving a plurality of fibers around a preparation scaffold and left for a period of time (e.g., overnight) in a water (in some cases, hot water, or ultrasonic) bath to dissolve the soluble component of a bicomponent fiber in embodiments where a bicomponent fiber is included in the fiber bundle 112 and remove any air. The fiber bundle 112 may then be prepared by twisting the fibers in the first arrangement. The twisting of the fibers in the first arrangement allows for the fiber bundle 112 to be the proper length to fit within the outer housing 104, as needed. In some embodiments, the fiber bundle 112 may then be secured to posts 122 via securing means 124 and left for a period of time (e.g., overnight) in a water (in some cases, room temperature water) bath (FIGS. 3A and 4A) or optionally in a bath of the matrix material 118. The securing means 124 may be, for example, plastic zip-ties. The posts 122 may be aluminum, for example.

[0061] In the method illustrated in FIGS. 4A-4E, an inner housing 114 (in this case a cable sheath) is pulled over a tube 126 (FIG. 4B). The fiber bundle 112 may then be pulled through the tube 126 via the securing means 124 (FIG. 4G). This arrangement allows for the tube 126 to be a barrier between the inner housing 114 and the fiber bundle 112. The end of the inner housing 114 and the fiber bundle 112 may then be held together while the tube 126 is pulled out, leaving the inner housing 114 directly over the fiber bundle 112 (FIG. 4D).

[0062] For both methods, the outer housing 104 may be filled with matrix material 118 using a disposable pipette or other method (FIG. 3B). The fiber bundle 112 (and optionally inner housing 114) are then placed in the outer housing 104 (FIGS. 3C and 4E). The outer housing 104 is then sealed closed using the cap 108 (FIG. 3D).

[0063] There are several benefits to this assembly process. First, when the fiber bundle 112 includes PVA, the filaments are protected by the PVA during fabrication. Secondly, as described previously, specific sizes of filaments can be chosen and blended in a targeted and parameterized ratio of sizes and quantities, and a selectable cross-section offilament is present in the final phantom 100. Third, if the fibers are bicomponent fibers, a soluble component of the fiber is removed in the water bath step of the production method. The volume is replaced with water / matrix material 118. Water immersion helps to replace any air pockets in the fiber material with water / matrix material 118. Air pockets are detrimental for MR imaging as they create artifacts.

[0064] While the applicant's teachings described herein are in conjunction with various embodiments for illustrative purposes, it is not intended that the applicant's teachings be limited to such embodiments. On the contrary, the applicant's teachings described and illustrated herein encompass various alternatives, modifications, and equivalents, without generally departing from the embodiments described herein. For example, while the teachings described and shown herein may comprise certain elements / components and steps, modifications may be made as is known to those skilled in the art. For example, selected features from one or more of the example embodiments described herein in accordance with the teachings herein may be combined to create alternative embodiments that are not explicitly described. All values and sub-ranges within disclosed ranges are also disclosed. The subject matter described herein intends to cover and embrace all suitable changes in technology.

Claims

CLAIMS:

1. A phantom for use with an MR imaging device, such as a clinical or pre-clinical MR imaging device, the phantom comprising: a sealable tube sized to fit within the imaging device; at least one fiber bundle removably inserted within the sealable tube, each of the at least one fiber bundles comprising a plurality of fibers; and a matrix material contained within the sealable tube and surrounding the at least one fiber bundle inside the sealable tube, the matrix material being an aqueous fluid and mimicking biological tissue or fluid properties; wherein one or more characteristics of the at least one fiber bundle and / or the matrix material are selected to evaluate imaging characteristics of the MR imaging device and / or to conduct an imaging study.

2. The phantom of claim 1, wherein the plurality of fibers are solid fibers, hollow fibers, or a combination of solid and hollow fibers.

3. The phantom of claim 1 or claim 2, wherein the characteristics of the MR imaging device include image resolution and / or image quality.

4. The phantom of any one of claims 1 to 3, wherein each of the plurality of fibers for a given fiber bundle are of a same size and a same type.

5. The phantom of any one of claims 1 to 3, wherein the plurality of fibers for a given fiber bundle are of differing sizes and / or differing types.

6. The phantom of claim 5, wherein the plurality of fibers for the given fiber bundle are blended together so that the given fiber bundle has a parametrized blend, or the plurality of fibers are co-located within the sealable tube.

7. The phantom of claim 1 , wherein each fiber of the plurality of fibers comprises a plurality of filaments, and each filament of the plurality of filaments is cylindrically shaped.

8. The phantom of any one of claims 1 to 7, wherein a tube axis extends from a first end of the sealable tube to a second end of the sealable tube, and the plurality of fibers are wound in the direction of the tube axis within the sealable tube.

9. The phantom of any one of claims 1 to 8, wherein the plurality of fibers are wound in multiple dimensions within the sealable tube.

10. The phantom of claim 9, wherein the plurality of fibers are interwoven, crossing and / or touching each other.

11. The phantom of any one of claims 1 to 10, wherein the matrix material includes a diffusivity modifier such that a viscosity of the matrix is adjusted to model a desired diffusivity for the phantom.

12. The phantom of any one of claims 1 to 11 , wherein the matrix material includes at least one additive to adjust a property of the phantom for imaging.

13. The phantom of claim 12, wherein the at least one additive comprises a salt to adjust a relaxivity of the matrix material or an antimicrobial agent to adjust a sterility of the matrix material.

14. The phantom of any one of claims 1 to 13, further comprising an inner housing removably inserted within the sealable tube, the inner housing being configured for holding the at least one fiber bundle within the sealable tube.

15. The phantom of claim 14, wherein the inner housing is a cable sheath or heatshrink tubing.

16. The phantom of any one of claims 1 to 15, further comprising at least one spacer removably inserted within the sealable tube, the spacer being configured for filling a volume of the sealable tube and maintaining the at least one fiber bundle in a desired area of the sealable tube when the at least one fiber bundle is inserted within the sealable tube.

17. The phantom of any one of claims 1 to 16, wherein the sealable tube is a nuclear magnetic resonance (NMR) tube or a conical tube.

18. The phantom of any one of claims 1 to 17, wherein at least a portion of the plurality of fibers are bicomponent fibers including island-in-the-sea fibers.

19. The phantom of any one of claims 1 to 18, wherein the plurality of fibers are sized on a cellular to tissue scale of a biological tissue.

20. A method of preparing a phantom that is defined according to any one of claims 1 to19, the method comprising: weaving the plurality of fibers around a scaffold to form a first arrangement and immersing the first arrangement in water for a first time period; twisting the first arrangement to form the at least one fiber bundle and immersing the at least one fiber bundle in water or optionally, matrix formulation, for a second time period; at least partially filling the sealable tube with the matrix formulation; inserting the at least one fiber bundle into the sealable tube and optionally filling any remaining empty volume of the sealable tube with the matrix formulation; and sealing the sealable tube.

21. The method of claim 20, further comprising inserting the at least one fiber bundle into the inner housing and inserting both the fiber bundle and the inner housing into the sealable tube.

22. The method of claim 20 or claim 21 , wherein the plurality of fibers are bicomponent fibers and the first arrangement is immersed in the water for the first time period to remove a soluble component of the plurality of fibers.

23. The phantom of any one of claims 1 to 19, further comprising a biological sample removably inserted within the sealable tube with the at least one fiber bundle.

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