Universal, modular temperature controlled MRI phantom for calibrated anisotropic and isotropic imaging including hollow fluid filled tubular textiles for calibrated anisotropic imaging

A universal, modular, temperature controlled MRI phantom for calibration and validation for anisotropic and isotropic imaging comprises an outer insulating shell configured to be received within an MRI chamber; an inner shell received within the outer insulating shell; a fluid conduits adjacent the inner shell for receiving temperature controlling fluid or gas cycling there-through; and a series of stacked layers of frames containing test points for the MRI phantom, each layer including at least one fiducial and including at least some anisotropic imaging test points in at least one frame and at least one isotropic imaging test point in at least one frame. The anisotropic imaging comprises hollow tubular textile fibers, wherein each hollow tubular fiber has an outer diameter of less than 50 microns and an inner diameter of less than 20 microns, wherein at least some hollow tubular fibers are filled with a fluid.

BACKGROUND INFORMATION

1. Field of the Invention

The present invention relates to a universal, modular, temperature controlled MRI phantom for calibration and validation for anisotropic and isotropic imaging which may include hollow fluid filled tubular textile-based MRI phantom for calibrated anisotropic imaging.

2. Background Information

This patent describes a technology innovation that could provide better calibration of brain imaging for brain trauma that impacts an estimated 4 million US citizens annually an estimated 300,000 veterans from recent military conflicts that have had brain trauma and potentially traumatic brain injury (TBI).

Since inception in the 70's, Magnetic Resonance Imaging (MRI) has allowed research and diagnostic imaging of humans and animals. MRI involves using a combination of high strength magnetic fields and brief radio frequency pulses to image tissue, typically by imaging the dipole movement/spin of hydrogen protons. MRI has long provided two and three dimensional imaging of internal tissue, tissue structure, and can provide imaging of functioning processes of tissue called “Functional MRI” or fMRI.

Diffusion MRI (or dMRI) is an MRI method or technology which allows the mapping of the diffusion process of molecules, mainly water, in biological tissue non-invasively. Since the earliest developments in the 80s, diffusion MRI, also referred to as diffusion tensor imaging or DTI, has seen extraordinary advancement. Diffusion tensor imaging (DTI) is important when a tissue—such as the neural axons of white matter in the brain or muscle fibers in the heart—has an internal fibrous structure analogous to the anisotropy of some crystals. Water will then diffuse more rapidly in the direction aligned with the internal structure, and more slowly as it moves perpendicular to the preferred direction. This is a well developed area of MRI research with several text books on these points, such as Johansen-Berg H. Behrens T. E. J., Diffusion MRI: From quantitative measurement to in-vivo neuroanatomy London Elsevier, 2009, and Jones D. K., Diffusion MRI: Theory, Methods, and Applications, New York: Oxford University Press, 2010.

The advanced work in MRI is also permitting highly detailed neural pathway mapping, sometimes known tractography or fiber tracking. Tractography or fiber tracking is a 3D MRI modeling technique used to visually represent neural tracts (or other biologic tracts) using data collected by DTI. Recent textbooks applying the methods to map white matter pathways include Oishi K., F. A. V., van Zijl P. C. M., Mori S.,MRI Atlas of Human White Matter, Amsterdam: Elsevier, 2010 and Catani M, Thiebaut de Schotten, M, Atlas of Human Brain Connections, New York: Oxford University Press, 2013.

One MRI technology is known as high definition fiber tracking, or HDFT, and is used to provide extremely highly detailed images of the brain's fiber network accurately reflecting brain anatomy observed in surgical and laboratory studies, as discussed in a report from the University of Pittsburgh, School of Medicine in the August, 2012 issue of Neurosurgery. The findings of this report show that HDFT MRI scans can provide valuable insight into patient symptoms and the prospect for recovery from brain injuries, and can help surgeons plan their approaches to remove tumors and abnormal blood vessels in the brain. One author Juan Fernandez-Miranda, M. D., assistant professor, Department of Neurological Surgery, Pitt School of Medicine, noted that “in deep brain surgery, the neurosurgeon may need to cut or push brain fiber tracts, meaning the neuronal cables connecting the critical brain areas, in order to get to a mass.” adding that “HDFT is an (MRI) imaging tool that can show us these fiber tracts so that we can make informed choices when we plan surgery.” Co-author of this report and co-inventor of the present invention, Walter Schneider, Ph.D., professor, Learning and Research Development Center (LRDC), Department of Psychology, University of Pittsburgh, who led the team that developed HDFT has elaborated that “a sophisticated MR scanner is used to obtain data for HDFT images, which are based on the diffusion of water through brain cells that transmit nerve impulses. Like a cable of wires, each tract is composed of many fibers and contains millions of neuronal connections. Other MR-based fiber tracking techniques, such as diffusion tensor imaging, cannot accurately follow a set of fibers when they cross another set, nor can they reveal the endpoints of the tract on the surface of the brain.” The instant application references the work discussed at the Schneider Laboratory at the LRDC (http://www.lidc.pitt.edu/schneiderlab/) for further background on the advancement, current status, and potential of anisotropic imaging and fiber tracking techniques with advanced MRI technologies, which work forms the background for the present invention.

Using advanced, non-invasive, in vivo diffusion imaging techniques combined with HDFT analysis and visualization, the Schneider Laboratory advances clinical research in the diagnosis and treatment of neurological pathology and trauma. The Schneider Laboratory works with the Neurological Surgery Department at UPMC to visualize fiber tracts within the brain in three dimensions in order to plan the most effective and least damaging pathways of tumor excision in patients suffering from various forms of brain cancer. Additionally, the Schneider Laboratory has been engaged in a Department of Defense and Veterans Administration funded HDFT projects to localize the fiber breaks caused by traumatic brain injuries (TBI), which cannot reliably be seen with the then current standard computed axial tomography (CAT or CT) scans or then available MRI scans in mild traumatic brain injury (mTBI), aiding the diagnosis and prognosis of patient brain trauma.

Others have developed fiber tracking technologies using MRI based scans. Consider, the S. Mark Taper Foundation Imaging Center at Cedars-Sinai which offers diffusion tensor imaging (DTI) fiber tracking and functional (fMRI) motor mapping using magnetic resonance imaging fused with 3D anatomical image of a brain to aid in surgical planning.

U.S. Pat. Publication No. 2006-0269107, now U.S. Pat. No. 7,529,397 developed by Siemens Medical Solutions USA, Inc. discloses methods for automatically generating regions of fiber tracking seeding points in diffusion tensor images.

The Johns Hopkins University's U.S. Pat. No. 8,593,142 discloses a system and associated method of automated fiber tracking of human brain white matter using diffusion tensor imaging.

U.S. Pat. Publication No. 2006-0165308 discloses a neighborhood relevance component that considers diffusion tensor matrices from neighboring pixels or voxels.

U.S. Pat. No. 8,076,937, developed by Koninklijke Philips Electronics N.V. of Eindhoven, NL, discloses diffusion data processing apparatus comprising a “segmenter” arranged to segment the diffusion tensor data according to at least one segmentation model representing at least part of a fiber bundle.

U.S. Pat. Publication No. 2007-0124117 discloses a system determining a direction of tracking a fiber based on a vector corresponding to a largest value of a set of values for a tensor.

U.S. Pat. Publication No. 2013-0279772, developed by BrainLAB AG of Feldkirchen, Germany (BrainLAB), discloses a method for finding fibers in image data of a brain which matches a functional atlas of the brain to an image data set which represents a medical image of the brain; performs functional atlas segmentation in order to segment the image data set into functional areas; and uses the segmented image data set to determine at least one seed point for a fiber tracking algorithm; and performing fiber tracking in order to find the fiber.

MRI Phantoms

As advanced MRI systems and technologies are developed, tested and/or placed in operation, the accuracy of the technology must be verified or validated. Validation may be defined as process wherein the accuracy of the technology/imaging algorithms is proven or verified. Further, the accuracy of the associated system must also be periodically verified (i.e., MRI system calibrated—also referenced as Quality Control aspects) to ensure original and ongoing accurate results and safe operation of the MRI systems. Generally speaking, calibration and/or test measurements for an MRI system are performed using an imaging phantom or more commonly referenced as a phantom. A phantom is any structure that contains one or more known tissue substitutes, or known MRI signal substances, forming one or typically more test points, and often is used to simulate the human body. A tissue substitute is defined as any material that simulates a body of tissue. Thus a phantom may be defined as a specially designed object that is scanned or imaged in the field of medical imaging to evaluate, analyze, and tune the performance of various imaging devices. A phantom is more readily available and provides more consistent results than the use of a living subject or cadaver, and likewise avoids subjecting a living subject to direct risk.

Numerous phantoms have been developed for various imaging techniques. For example, U.S. Pat. No. 6,744,039 relates to a fillable phantom which includes a container, a porous medium within the container, and a connector for filling the container with a radioactive solution.

U.S. Pat. No. 6,720,766 relates to a thin film phantom for testing and measuring the performance of magnetic resonance imaging (MRI) and x-ray computed tomography (CT) imaging systems. The phantom includes a planar medium and a plurality of individually sub-resolvable scatters having preselected magnetic resonance properties within a pattern of resolvable regions on the surface of the medium.

U.S. Pat. No. 6,409,515 describes a phantom which includes a plurality of segments having unique identifiers, the segments joining together to form a polyhedron around an inner plate.

Electronics and Telecommunications Research Institute's U.S. Pat. No. 7,667,458 discloses a phantom for Diffusion Tensor Imaging (DTI) to measure the main physical quantities of diffusion tensors, such as diffusion anisotrophy, a diffusion principal axis and a route of the diffusion principal axis, and to evaluate the accuracy of DTI. The phantom for diffusion tensor imaging includes: an outer container providing a space; materials for diffusion measurement located in the space of the outer container and formed of bunches of micro-tubes; and materials for fixing located in the space of the outer container to fix the materials for diffusion measurement to a specific location. The micro-tubes in this phantom design may be stems of various plants such as leaves of vegetables or a bamboo stem.

The Medical College of Georgia Research Institute, Inc.'s U.S. Pat. No. 8,134,363 discloses a phantom for use with diffusion MRI comprising a plurality of anisotropic arrays stacked in a plurality of parallel rows to form a macro-array, wherein each of the arrays includes a plurality of typically glass capillaries (ID 10-90 microns) with each of the capillaries holding a first fluid; and a housing, holding a second liquid.

U.S. Pat. No. 8,643,369 describes an anisotropic diffusion phantom for the calibration of any diffusion MR-DTI imaging sequence the form of an array of thin glass plates separated with H2O layers, wherein the layers have a thickness of about 10 microns.

BrainLAB's U.S. Pat. Publication No. 2006-0195030, now U.S. Pat. No. 7,521,931, discloses a phantom for use with diffusion tensor imaging which includes a container and a plurality of structures within the container. The structures have anisotropic properties, wherein when the phantom is subjected to diffusion tensor imaging, the structures provide data that is recognized as fiber bundles. The structures can be formed, for example, from cloth tape, silk, wood, glass fibers cord (synthetic and viscose) and/or “microfibers”.

The Department of Health and Human Services published U.S. Pat. Publication No. 2012-0068699, which discloses a phantom calibration body for calibrating diffusion MRI device which includes a homogeneous aqueous solution that contains a mixture of low molecular-weight and high molecular-weight polymers housed in a container.

Alexander J. Taylor, “Diffusion Tensor Imaging: Evaluation of tractography algorithm using ground truth phantoms,” Virginia Tech, May 2004 describes the creation of a physical phantom to evaluate the performance of tractography algorithms, which are used to estimate tissue microstructure. In creating this phantom, Taylor used polytetrafluoroethylene (PTFE) capillary tubing with an inner dimension (ID) of over 300 microns and an outer diameter of over 700 microns. Multiple segments of the tubing were cut, filled with water, and assembled into sheets with a 90 degree crossing pattern. The capillary sheets were placed in a small plastic container and surrounded by gelatin to mitigate air related susceptibility artifacts in the images.

Ching-Po Lin, Van Jay Wedeen, and Jyh-Horng Chen, “Validation of diffusion spectrum magnetic resonance imaging with manganese-enhanced rat optic tracts and ex vivo phantoms,” Neorolmage, vol 19 (2003) 482-495, discusses creation of a phantom to be used to compare the effectiveness of DTI and Diffusion Spectrum Imaging (DSI) for correctly determining the orientation of crossed axonal fibers. Lin used PTFE “microbore” tubing with ID 50 micron and OD 350 micron. Segments of the tubing were filled with water and assembled into sheets. Layers of these sheets were stacked at 90 and 45 degrees in reference to each other in an interleaved fashion. The structures were then secured to a firm plastic plate.

Elisabeth A. H. von dem Hagen and R. Mark Henkelman, as described in “Orientational Diffusion Reflects Fiber Structure Within a Voxel,” Magnetic Resonance in Medicine, 48: 454-459 (2002), were possibly the first individuals to evaluate the effectiveness of DTI for determining fiber orientation using a physical model. This phantom also consisted of PTFE “ultramicrobore” tubing having ID 50 micron and OD 350 micron. The capillaries were filled with water by a gluing a 22½-gauge needle to each segment. After being filled, the capillaries were sealed by melting both ends and removing the needle. The capillaries were placed in three different orientations, namely, aligned, coiled, and random and placed inside borosilicate glass tubes. For discussion of similar phantoms see Atiba Fitzpatrick, “Automated Quality Assurance for Magnetic Resonance Image with Extensions to Diffusion Tensor Imaging” Virginia Polytechnic Institute, June 2005.

Poupon, C., Rieul, B., Kezele, I., Perrin, M., Poupon, F., & Mangin, J F. (2008), New diffusion phantoms dedicated to the study and validation of high-angular-resolution diffusion imaging (HARDI) models. Magnetic Resonance in Medicine, 60, 1276-1283; discloses work developed in part at General Electric Healthcare and Institut d'Imagerie Biomedicale in Gif-sur-Yvette France and utilized 20 micron diameter acrylic fibers bundled together in a two part frame forming a 45 degree and 90 degree crossing phantom and in a fiber density of 1900 fibers/mm2.

The current needs for MRI phantoms for anisotropic imaging for validating and calibrating fiber tracking technologies and systems were also recently elaborated in the May 2014 International Society for Magnetic Resonance in Medicine (ISMRM) meeting, see Michael A. Boss, Thomas L. Chenevert, Daniel P. Barboriak, Mark A. Rosen, Edward F. Jackson, Alexander R. Guimaraes, David E. Purdy, Thorsten Persigehl, Hendrick Laue, Marko K. Ivancevic, Gudrun Zahlmann (2014) QIBA Perfusion, Diffusion, & Flow MRI Technical Committee: Current Status Poster proceedings ISMRM meeting Milan Italy May 2014, (see www.ismrm.org).

Carolin Reischauer, Phillipp Staempfli, Thomas Jaermann and Peter Boesiger (2009) Construction of a Temperature Controlled Diffusion Phantom for Quality Control of Diffusion Measurements; Journel of Magnetic Resonance Imaging 29:692-698 describes a temperature controlled diffusion phantom using dyneema fibers which are braided strands of polyethylene

Juneja, Vaibhav, “Novel Phantoms and Post Processing For Diffusion Spectrum Imaging” (2012), UT GSBS Dissertation and Thesis (Open Access) Paper 240 .describes a crossing fiber phantom constructed of capillary filled hollow fibers of 50 micron inner diameter and 150 micron outer diameter.

Physical phantoms, as described and discussed above, provide a different balance between ground truth control and realism, to that provided by computer simulations. The above identified patents and patent applications are incorporated herein by reference and these together with the cited papers, and supporting work discussed therein, firmly establish the continued need for effective MRI phantoms for anisotropic and isotropic imaging for validating and calibrating fiber tracking technologies and systems.

SUMMARY OF THE INVENTION

One aspect of this invention is directed to a cost effective, efficient, universal, modular, temperature controlled MRI phantom for calibration and validation for anisotropic and isotropic imaging comprising an outer insulating shell configured to be received within an MRI chamber; an inner shell received within the outer insulating shell; a fluid conduit adjacent the inner shell for selectively receiving temperature controlling fluid or gas cycling there-through; and a series of stacked layers of frames containing test points for the MRI phantom, wherein each layer includes at least one fiducial and further including at least some anisotropic imaging test points in at least one frame and at least one isotropic imaging test point in at least one frame.

One aspect of this invention is directed to a cost effective, efficient, MRI phantom for calibrated anisotropic imaging comprising hollow tubular textile fibers, wherein each hollow tubular fiber has an outer diameter of less than 50 microns and an inner diameter of less than 20 microns, wherein at least half of the hollow tubular fibers are filled with a fluid.

One aspect of this invention is directed to a cost effective, efficient, MRI phantom for calibrated anisotropic imaging comprising hollow tubular textile fibers, wherein at least some of the hollow tubular fibers are filled with a fluid, wherein at least some of the hollow tubular fluid filled textile fibers are formed in fasciculi, also called fascicules, bundles or threads, wherein at least some fasciculi are combined into tracks that are supported in at least one routing frame which includes a plurality of distinct track starting locations at one end thereof and a plurality of aligned track ending locations at an opposed end thereof and tracks extending from the starting locations to the ending locations, wherein substantially all of the tracks end in an ending location that is not aligned with the respective track's starting location.

The phantom of the invention operates at the biologically meaningful range of sub 20 micron hollow fibers that are filled with fluid (e.g. water), that can control the packing density, micron level crossing structure of curves, crossings, merging and kissing in 2 and 3D structures to closely match human tissue. The phantom of the invention uses textile fibers in bundles matching fasciculi and tracts of the human brain. The phantom of the invention can be manufacture with tight precision and with the geometries needed. The phantom of the invention may be manufactured exhibiting the diffusion properties (e.g., the factional anisotropy (FA) and apparent diffusion coefficient (ADC)) in the human tissue range as a commercially viable scale and cost of filling the hollow fibers.

One aspect of this invention is directed to a cost effective, efficient, MRI phantom for calibrated anisotropic imaging comprising hollow tubular textile fibers, wherein at least some of the hollow tubular fibers are filled with a fluid, wherein at least some of the hollow tubular fluid filled textile fibers are formed in fasciculi, wherein at least some fasciculi are combined into tracks that are supported in at least one fixed frame, wherein the phantom includes a plurality of alignment targets visible to the MRI, and wherein the phantom is configured to be worn by a patient in the MRI.

One aspect of this invention is directed to a cost effective, efficient, MRI phantom for calibrated anisotropic imaging comprising an MRI phantom for calibrated anisotropic imaging comprising hollow tubular textile fibers, wherein at least some of the hollow tubular fibers are filled with a fluid, wherein at least some of the hollow tubular fluid filled textile fibers are formed in fasciculi, wherein at least some fasciculi are combined into tracks that are supported in at least one crossing density frame which includes at least three angle fiber crossings across the fixed frame, wherein the angle fiber crossings include a plurality of distinct fiber densities.

One aspect of this invention is directed to a cost effective, efficient, MRI phantom for calibrated anisotropic imaging comprising an MRI phantom for calibrated anisotropic imaging comprising hollow tubular textile fibers, wherein at least some of the hollow tubular fibers are filled with a fluid, wherein at least some of the hollow tubular fluid filled textile fibers are formed in fasciculi, wherein at least some fasciculi are combined into tracks that are supported in at least one crossing density frame which includes at least three angle fiber crossings across the fixed frame, wherein the angle fiber crossings include a plurality of distinct fiber densities.

One aspect of this invention is directed to a cost effective, efficient, MRI phantom for calibrated anisotropic imaging comprising hollow tubular textile fibers, wherein at least some of the hollow tubular fibers are filled with a fluid, wherein at least some of the hollow tubular fluid filled textile fibers are formed in fasciculi, wherein at least some fasciculi are combined into tracks that are supported in at least one a fiber density frame which includes fiber density variations across the fixed frame, whereby the fibers/unit area in the fixed frame are provided at distinct known varied amounts at least three distinct test points across the fixed frame.

One aspect of this invention is directed to a cost effective, efficient, MRI phantom for calibrated anisotropic imaging comprising hollow tubular textile fibers, wherein at least some of the hollow tubular fibers are filled with a fluid, wherein at least some of the hollow tubular fluid filled textile fibers are formed in fasciculi, and wherein at least some fasciculi include interstitial fluid, and wherein hollow tubular fluid and the interstitial fluid is formed of both water and deuterium oxide. Most commonly deuterium oxide will be within the fibers, although deuterium oxide as intersticial fluid is possible.

These and other aspects of the present invention will be clarified in the description of the preferred embodiment of the present invention described below in connection with the attached figures in which like reference numerals represent like elements throughout.

BRIEF DESCRIPTION OF THE PREFERRED EMBODIMENTS

This invention, in one embodiment thereof, is directed to an MRI phantom10for calibrated anisotropic imaging comprising hollow tubular textile fibers12, wherein each hollow tubular fiber12has an outer diameter of less than 50 microns and an inner diameter of less than 20 microns, wherein at least half, and preferably at least 70%, of the hollow tubular fibers are filled with a fluid14. Fluid, within the meaning of this application includes liquids (e.g., water and deuterium oxide) and gels (e.g., hydrogel), but not gasses. The fluid filled hollow tubular textile fibers12for calibrated anisotropic imaging may form part of a universal, modular, temperature controlled MRI phantom10, shown inFIGS. 11A-E, for calibration and validation for anisotropic (HDFT) and isotropic imaging (standard diffusion). Universal within the meaning of this application defines that the MRI phantom10is configured to fit substantially any MRI system and can be used for calibrated anisotropic imaging and calibrated isotropic imaging. Modular within the meaning of this application defines that the MRI phantom10is configured to receive distinct user selected test points therein, which preferably includes the fluid filled hollow tubular textile fibers12with multiple test points for calibrated anisotropic (HDFT). Temperature controlled references that the MRI phantom10is configured to maintain a substantially constant temperature, within +−8 degrees, throughout the MRI testing. The cost effective, efficient, universal, modular, temperature controlled MRI phantom10for calibration and validation for anisotropic and isotropic imaging comprises an outer insulating shell200configured to be received within an MRI chamber; an inner shell210received within the outer insulating shell200; fluid conduits220adjacent the inner shell210for receiving temperature controlling fluid or gas cycling there-through; and a series of stacked layers230of frames20containing test points for the MRI phantom10, including at least some anisotropic imaging test points in at least one frame20and at least one isotropic imaging test point in at least one frame20.

The details of the universal, modular, temperature controlled MRI phantom10for calibration and validation for anisotropic and isotropic imaging ofFIGS. 11A-E, is better explained following the description of the MRI phantom10of the present invention for calibrated anisotropic imaging comprising the fluid filled hollow tubular textile fibers12, detailed in connection withFIGS. 1A-10C.

The textile fibers12used in selected frames10of the MRI phantom10of the present invention may be effectively formed from polymer fibers. These hollow textile fibers12exhibit the required characteristics and represent a key step for creating a phantom10that properly mimics the human brain for anisotropic imaging. These polymer fibers12generally may include polyamide nylon; PET or PBT polyester; phenol-formaldehyde (PF) polyvinyl chloride fiber (PVC) vinyon; polyolefins (PP and PE) olefin fiber; acrylic polyesters; pure polyester PAN fibers, aromatic polyamids (aramids) such as Twaron, Kevlar and Nomex; polyethylene (PE), eventually with extremely long chains/HMPE (e.g. Dyneema or Spectra); Elastomers, e.g. spandex; urethane and polyurethane fibers; and Elastolefin. In the selection of fiber material of fibers12, the material hydrophobicity is very important as hydrophobic materials have a higher fractional anisotropy. Further it is desirable if the material configuration or structure is similar to the axons with regard to MRI response, such that the hollow synthetic fibrous materials can effectively mimic the configuration of the axons, wherein each hollow tubular fiber12has an outer diameter of less than 50 microns and an inner diameter of less than 20 microns. The outer diameter of the fibers12is generally less than 30 microns and often less than 25 microns, or 20 microns. The inner diameter may also be less than 15 microns, and even 5 microns or less.

FIGS. 1A-Dillustrates representative hollow polymer textile fibers12useful for forming filled fluid fibers12for anisotropic imaging in the phantom10of the present invention.FIG. 1Ais an image of polypropylene based fiber12for forming the phantom10of the present invention wherein the inner diameter measured as shown is about 8.4 microns and the wall diameter is 13 microns.FIG. 1Bis an image of polyester based fiber12for forming the phantom10of the present invention wherein the inner diameter measured as shown is about 3.15 microns and the wall diameter is 4.36 microns.FIGS. 1Cand D are images of polyamide based fiber12for forming the phantom10of the present invention wherein the inner diameter measured as shown is about 5.3 microns and the wall diameter is about 6.5 microns.

Hollow fibers similer to fibers12of phantom10are often used in membranes for ultra filtration, artificial kidneys, artificial lungs, oxygenation devices etc. Round, squares and trilobals are examples of geometries used to produce hollow fibers and which is discussed further in Omeroglu, S. Karaca, E., & Becerir, B. (2010), Comparison of Bending, Drapability and Crease Recovery Behaviors of Woven Fabrics Produced from Polyester Fibers Having Different Cross-sectional Shapes, Textile Research Journal, 80, 1180-1190.

The hollow fibers12may be produced by extrusion technique with a spinneret forming the desirable hollow configuration. Thus there is an additional dimension from ordinary fibers, namely the inner diameter that is not present in many textile fibers. This formation is discussed further in Oh, T., Lee, M., Kim, S., & Shima, H. (1998). Numerical Simulation of the Melt Spinning of Hollow Fibers. Textile Research Journal, 68, 449-456. The spinneret geometry, coagulant flow-rate, polymer solution viscosity and flow rate, and air gap affect the geometry of the hollow fibers. The final fiber size is determined by main factors as the draw ratio, which controls the desired outer diameter; the polymer-to-bore volumetric flow rate, which controls the ultimate outer-to-inner fiber diameter ratio; and, the dimensions of the annular spinneret hole. For further detailed discussion see Su, Y. (2007). Theoretical Studies of Hollow Fiber Spinning Thesis for Doctor of Philosophy Degree in Engineering. The University of Toledo.

One important aspect of the invention is filling the fibers12with fluid14, namely water (H2O) or deuterium oxide (D2O), also called heavy water. The filling of the fibers12is not a trivial matter due to the small diameter of the inner diameter and the hydrophobic material. In order to obtain desired MRI results, at least half and preferably at least 70% of the fibers12of the phantom10will be filled with fluid14. The 50% fill rate is believed to be the minimum to yield an effective MRI test point associated with filled fibers12, and 70% is a more meaningful minimum based upon the desired result of yielding an effective MRI test point associated with filled fibers12. A production standard for verified filling procedures of 80%, 90%, 95% and higher fill rate may be used to verify the effectiveness of the filling procedure (rather than a using a lower percentage that is associated with the effectiveness of the MRI test points themselves), and these higher fill rates are possible with the following procedures. Several considerations should be taken into account in filling the fibers12. First removing impurities from the fluid14via passing fluid14through one or more micro-filters can facilitate filling, as can controlling the filling environment (i.e. a dust free/minimal dust environment, such as a clean room or pseudo-clean room), as entrained dust particles may be larger than the inner diameter or sufficient in size to hinder filling. Pressure assisted filling including positive pressure on the fill side (via plunger arrangement or other pressurized source of fluid14) and possibly reducing pressure on the other side of the fiber12can further be implemented to facilitate the filling process. Centripetal force may be utilized with the fibers12located along a rotating disc and secured to a filling hub, whereby the centripetal force will increase from the center to help move the fluid14along the fibers12.

In addition to these considerations for facilitating filling of fibers12, some consideration is made to the original manufacturing and shipping of the fibers12. Specifically, steps are avoided that introduce inner diameter restrictions, i.e. crimps in the fibers12. As discussed below, the individual fibers12will be grouped into fascicule16, which can also be called threads or bundles. In textile manufacturing using these hollow fibers, such threads are commonly formed as yarns of many fibers (e.g., 64). Conventional winding tension on the yarns can crimp the outer layer of fibers12and detrimentally effect filling of fibers12with fluid14in the present invention. It is still possible for fascicule16to be formed through larger sets of fibers12, provided this does not introduce an undesired MRI artifact and they do not crimp any of the fibers12.

For relatively short lengths of fibers12and fascicule16, capillary action can effectively be used for filling the desired fibers12with fluid14. The simplest technique for filling fibers12with capillary action is to submerge the fibers12within the desired fluid14for a desired orientation. A fiber holding frame can be implemented to assist in holding the fibers12straight to facilitate capillary action and to allow for a desired orientation within the fluid14. Naturally capillary action filling does not require the complete submersion of the fibers12, as such can be accomplished if only one end of fibers12is submerged within the fluid14. Capillary filling action of the fibers12can be optimized through the combined use and/or consideration of short lengths of fibers12, filtering of filling fluid14(distilled water, deuterium), treating of filling fluid for viscosity adjustment with MR compatible added materials, pressure control to facilitate capillary action, temperature to facilitate capillary action, sufficient dwell time for completion of capillary action, orientation of the fibers to facilitate capillary action, pre-treatment of fibers (e.g., cleaning) to facilitate capillary action, control of cutting of fibers to maintain opening that facilitate capillary action (do not crimp or minimize opening), and utilization of textile manufacturing techniques of hollow fibers that minimize knots, twisting, kinking or the like that otherwise inhibits the fiber12's lumen.

The use of capillary action for fluid filling allows for the possibility of forming the desired test pattern or test block of fibers12and fascicule16prior to the filling procedure (referenced as making dry test blocks), and then followed by filling, generally by submersion of the test block within the fluid14. Thus the method of building an MRI phantom10with capillary action filled hollow fibers12may effectively comprise the step of making dry test blocks or patterns with fibers12, followed by filling the fibers12of the test pattern/block with fluid14via capillary action and then followed by quality control techniques to verify filling (e.g. visual of significant sample size). The quality control technique may use image analysis to verify filling via visual contrast. Alternatively the fibers12may first be filled with fluid14via the capillary action and the filling procedure checked/verified and then the test pattern formed with the verified filled blocks. A final process arrangement is to fill the fibers12then form the test blocks, then verify the filling such as by MRI image analysis. Regardless or the order, capillary action has proven effective for filling fibers12, but verification of the filling procedure is still desirable following filing either before or after the test block is formed.

Longer fiber12or fascicule16lengths may not be appropriate for capillary filing. Another effective process for filling the fibers12useful for longer fibers12is described in connection withFIGS. 8A-8E.FIG. 8Aillustrates a rotational jig or core100to assist in filling the fibers12. The core100includes a shaft102that can be coupled to a motor and encoder to count the wraps. The core100includes a groove104around the periphery within which the fibers12are wrapped. The core100include two pairs of gasket molds106on each side of the core100which are used to form silicone gaskets108as will be described. In operation the fibers12are wrapped around the core100within the groove104. In this embodiment the fibers12are grouped in fascicle16and the fascicle16is being wrapped around the core100within the groove104.

With every wrapping or every few wrappings of the fascicle16formed of the fibers12, the fibers12are coated with silicone, or similar anchor substance, in the area of the molds106to assure the fibers12are coated and the gasket108is complete when formed. Once the number of wrappings is sufficient to form the desired track18, the wrapping ceases. Then outer mold halves are coupled to the core100above each mold106and silicone is injected into the molds106to form the complete gaskets108. The fascicles16may be severed at the ends of the core100to form two unfilled, untrimmed tracks18each with a pair of silicone gaskets108as shown inFIG. 8B.FIG. 8Cshows an unfilled, untrimmed track18with a pair of silicone gaskets108removed from the core100.

The silicone gasket108serves several purposes, the first of which is to provide a supporting substrate for trimming the fibers12such that the individual fibers remain open and are not crushed, as the cannot be filled if they are crushed. The unfilled, untrimmed track18with a pair of silicone gaskets108are trimmed by cutting through the gaskets108as shown inFIG. 8Dand the trimmed filling surface110will exhibit the open hollow fibers12surrounded by silicone forming gasket108. Cutting perpendicular to the fibers12with a sharp blade is preferred.

The second purpose of each gasket108is to allow for attachment of that trimmed filling surface110within a filling chamber of a coupling member112. The gasket108may provide a face seal against a corresponding surface of the coupling member112or the peripheral edge of the gasket108can seal against an inner peripheral edge of the coupling member112, or both. A clamping member114will help secure the gasket108in place with clamping bolts (not shown) to provide desired coupling pressure. The coupling member112includes a conduit tip116to attach to a source of pressurized fluid4which has been filtered, and/or at the trailing end the gasket108may attach to a coupling member112in which the tip116is coupled to a vacuum source if desired. The fibers12within track18may thus be filled simultaneously and efficiently.

Following filling of the fibers12, the distal end of the track18of the fibers12may be sealed such as by dipping in silicone, thereby closing the open ends of the fibers12at the distal end. The remaining open end at the proximal end can then be removed from the filling unit and sealed in a similar manner to form the filled hollow tubular textile fibers12of the phantom10. As noted above, a number of additional aspects may be used to facilitate filling, such as vacuum/lower pressure on the opposed open ends during filing, centripetal force, temperature controls to facilitate filling, additives that facilitate filling the small diameter hollow fibers12. The extraneous parts of the gaskets108, such as those extending beyond fascicules16used for the earlier sealing may be trimmed, if desired. Other closing techniques may be considered such as crimping, heat sealing or combinations thereof. The advantage of crimping and heat sealing and combinations of these is that neither introduces another MRI signature or artifact into the system. In the discussion below the usable portion of the filled fibers12will be that located between the gaskets108, although the (trimmed) gaskets108may also serve to assist in mounting of the track18to the desired fixed frame20of the phantom10.

The core100described above included a pair of usable tracks18on each side. Alternatively the core100may be modified to include a single gasket mold106and the operation can wrap the long fiber12/fascicles16around the core100having a circumference generally of the desired fiber12length. The wrapped fibers12will be coated with silicone periodically at a small segment of the core100with the single mold106. When the fibers12are present in a desired amount for the filling apparatus, such as sufficient to form a track108, the single gasket108is formed and the fibers12are cut within in the middle of the single silicone gasket, thereby forming an unfilled track18with two silicone gaskets108at each end. The trimmed unfilled track18may be filled as described above. As noted above, a number of additional aspects may be used to facilitate filling, such as vacuum/lower pressure on the opposed open ends during filing, centripetal force, temperature controls to facilitate filling, and additives that facilitate filling the small diameter hollow fibers12.

FIGS. 9Aand B illustrate an alternative filling arrangement that is by groups of individual fascicules16, and this is also useful for longer runs or lengths of fibers12. In this filling arrangement a two piece mold120with top filling opening122and which further includes a series of individual openings there-through on the face thereof in which individual fascicles16are advanced. One side of the mold120includes a cylindrical coupling member124to be coupled to a fluid source. Around each opening for the individual fascicules16are plastic cylindrical mold extensions126. Once the fascicules16are threaded through the openings, the mold120is filled with silicone with the mold extensions126serving to allow the silicon to advance around each individual fascicule16. Then the end is trimmed by slicing through the mold extensions126, the silicon and each individual fascicule16to form the open end filling face110within the coupling member124. The coupling member124can be coupled to a source of fluid14and the fascicules16filled as above. The distal end may be sealed in any convenient fashion as described above. The sealing of the end with mold120can be accomplished downstream from the mold120at the proximal end and the mold120then removed from the fascicules16/track18. The mold120ofFIGS. 9Aand B allows the filling of individual fascicules16as desired and may better accommodate larger variations in length of filled fibers12.

Other modifications of these filling techniques may also be used as well as combining features thereof. There should be validation of the filling process regardless of the filling process utilized (or whether it is before or after the test blocks are formed), which can be accomplished by a number of methods. Weighing of the filled fascicule16may be the most efficient. Direct examination of a representative sample of fascicules16is also an acceptable validation method, wherein submersion of distal ends of fascicules16and associated fibers12in contrasting media, such as oil or other similar substance, may assist in direct observations of water filling. MRI image analysis of the filled tubes and/or the formed test blocks may be acceptable as a verification process. As noted above at least ½ and preferably at least 70% fibers12of the phantom10of the present invention are filled with fluid14as minimums for forming effective test points for filled fibers12, and the above filling techniques easily allow for 80%, 90% and 95% fill rates to be easily accomplished without undue costs. The higher fill rates 80%, 90% and 95% may be used as production standards to yield more definitive phantoms10.

Other filling techniques than described above may be implemented, such as filling individual fibers12at manufacturing. Further, although filled in a combined fascicule16or track18, the individual filled fibers12may later be separated in a specialized phantom construction as desired.

As noted above the fibers may be filled with water or deuterium oxide. Other possibilities include water with substances to improve viscosity for filling. Further other elements are possible to be added to the water outside of merely to facilitate filling of the fibers12. For example materials suspended in water (e.g. iron to examine susceptibility in vascular shapes), provided the suspended particles do not detrimentally effect filling and are suitably MRI compatible. T

Restricted and Hindered Water Differentiation

The phantom10for calibrated anisotropic imaging using fluid14filled fibers12provides precise and repeatedly manufactured simulated axonal diffusion structures to separate and quantify simulated intra-axonal water (i.e. fluid14within the fibers12), which has been termed “restricted” in the MRI literature, and simulated extra-axonal water, also called interstitial fluid, (i.e. fluid between fibers12in a given fascicule16), wherein water between the axons is termed “hindered” water within the MRI literature, and free water or isotropic diffusion. The phantom10for calibrated anisotropic imaging using fluid14filled fibers12is composed of hollow fibers12which are micron-scale textiles manufactured and arranged in test blocks or patterns in controlled crossing and packing densities in two and three dimensions. The goal is to provide ground truth quantification of axonal tract structures, as well as to quantify accuracy and interpretability of diffusion measurements across vendors, instruments, acquisition, and analysis procedures.

The phantom10for calibrated anisotropic imaging using fluid14filled fibers12of the invention provides the ability to measure both the simulated intra-axon (water14within fibers12) and extra-axon water (water between fibers12) to allow quantification of water that is intra-axonal that allows estimation of the axonal areas of a tract18and the integrity of the fibers12. The measurement of intra-axonal water is believed to be critical in the detection of pathologies, such as traumatic brain injury (TBI), with diffuse axonal injury (DAI) that causes intra-axonal water which is a serious often permanent problem, and increases intra-axonal water through edema often a transitory problem. It is believed to be important that the MRI scanner sensitivity to these two types of water change in a tract can be determined. The concept of intra-axonal water is referred to in the literature (see Assaf, Y. and P. J. Basser,Composite hindered and restricted model of diffusion(CHARMED)MR imaging of the human brain. Neuroimage, 2005. 27(1): p. 48-58) as restricted water. That is the water diffusion is restricted by the tube walls to only diffuse in one dimension along the core of the tube. This is, in fact, the key physical feature that allows anisotropic diffusion imaging to selectively image, and to non-invasively quantify, axonal tissue from other tissue. Axons as a tissue type have enormous diameter to length ratios (e.g., 1 micron diameter 10 cm length hence a 10,000 to one ratio). This high ratio allows the MRI machine to be tuned to measure axonal water selectively and not have the measurement confounded by all the other types of water in the brain (or spine) by the many cells intercellular water chambers. However there is a second type of water, namely the extra-axonal water or hindered water. This is the water between the axons. Depending on the compaction of the axons, the spacing between the fibers12can closely mimic the diffusion of the intra-axonal (restricted water) but as the extra-axonal water exceeds the intra-axonal water the anisotropic diffusion rapidly drops. It is believed to be critical for an MRI system to accurately measure the axonal integrity of a tract (as in TBI induced diffuse axonal injury) to distinguish intra-axonal water from extra-axonal water effects. The phantom10for calibrated anisotropic imaging using fluid14filled fibers12according to the present invention is the first phantom technology that supports this critical measurement capability.

Filling the 20 micron, and lower, inner diameter fibers12with fluid14provides ground truth for the presence of restricted water (water within simulated axons or fibers12). In contrast, filling selected fibers12with D2O alters the Larmor resonance frequency of the water molecules, eliminating the restricted water signal from the MRI image without altering the chemical or structural properties of the fiber12. This allows, for the first time, the opportunity to scan the same simulated axonal structures formed by fibers12with the restricted water present (H2O filled) or “removed” (D2O filled).

The phantom10will provide a “ground truth” value for variables used to model diffusion in dMRI, with direct relationship between fiber12construction and anatomical structures (e.g., similer/overlapping tube diameters, tract shapes, and interstitial spaces and fluids). This phantom10allows the quantification of measurement error in the pipeline. The textiles forming fibers12are stable, such that they can be disassembled from the phantom10and re-measured to verify maintenance of the water content over years of storage and use.

It is noted that the theoretically most effective metric for detecting TBI is the quantification of loss of intra axonal water that is lost in diffuse axonal injury (DAI, the hallmark of TBI). Thus in HDFT the goal is to quantify, for a given patient's tract, the percentage of loss (10%, 20%, etc of expected intra axonal water in a tract). It is critical that such systems do not falsely interpret other factors (edema, brain size, tract shape variation, shifted crossing locations) as axonal volume loss. The phantom10for calibrated anisotropic imaging using fluid14filled fibers12allows for validation of the HDFT system and calibration of the particular MRI system.

FIG. 2shows the construction of a modular MRI phantom10for calibrated anisotropic imaging comprising hollow tubular textile fibers12filled with a fluid14, typically water. The textile fibers12are formed in fascicle16as discussed above and fasciculi16are combined into tracks18that are supported in fixed frames20within the phantom10. The particular number of fibers12in each of the threads or fasciculi16may largely depend upon manufacturing and filling criteria, but 64 fibers per fascicule16has been effectively used. The number of fasciculi16within a track18depends upon the size of the fascicule16and the desired size of the track18for the intended simulation. The phantom10for calibrated anisotropic imaging using fluid14filled fibers12ofFIG. 2is formed as a frusto-spherical shell mounting a plurality of fixed frames20. The frusto-spherical shape allows for easy mounting within an MRI. The interior of the shell can be filled with water, or heavy water, which can serves as the interstitial fluid between fibers12of fascicule16. As noted above, selective filling of fibers12with heavy water allows for differentiation between hindered and restricted fluid.

The fixed frames20will have distinct configurations depending upon the desired phantom component being constructed, providing the modular aspect to the phantom10ofFIG. 2. All of the fixed frames20are formed out of material acceptable for the MRI environment that does not create artifacts in the scanned image, except for the inclusion of desired fiducial elements on the frame20. The fixed frames20described herein will allow for an easy mechanism to obtain the desired compression of the tracks18of fascicules16of fibers12. For most configurations the fibers12need to be compressed to at least 4× the maximum compression volume, which is the volume in which substantially all of the interstitial or extra-axonal water is removed from between the fibers. Some MRI technologies may have difficulty tracking above 2× the maximum compression volume. The fixed frames20are typically formed of two main bodies that are bolted together via nylon bolts or the like. In addition to clamping the frame portions together the bolts may be constructed to form fiducial elements for the phantom10. Three dimensional printers allows for rapid production of new frames20in any desired configuration provided the printing material does not introduce undesirable MRI artifacts. Changes to specific fixed frames20are thus easily made.

Fiber Crossing Frame

FIGS. 3A-3Dillustrate a fixed frame20formed as a fiber crossing frame which includes at least three distinct angle fiber crossings across the fiber crossing frame20. The fixed frame20ofFIGS. 3A-Dis formed of two halves that are bolted together to provide the desired compression on the tracks18extending there-through, which tracks18are best shown inFIG. 3D. The fiber crossing frame20includes a lower tract pathway22supporting a lower track18within the fixed frame20, an upper tract pathway22supporting an upper track18within the fixed frame20which is substantially parallel with the lower track18across the fixed frame20and an intermediate tract pathway22between the upper tract pathway22and the lower tract pathway22supporting an intermediate track18between the upper track18and the lower track18, and wherein the intermediate track18crosses the upper and lower tracks18at least at three distinct angles. Specifically, as shown the three distinct angles of the fiber crossings of the fiber crossing frame ofFIGS. 3A-3Dinclude 90 degrees, 45 degrees and 30 degrees (or 60 degrees), as shown. The fiber crossing frame construction shown is an easily produced construction as it only requires three tracks18, rather than laying out individual crossing fasciculi16or interwoven fibers12. The distinct test points for the crossing are, of course, where the intermediate track18crosses the parallel upper and lower tracks18.

The fiber crossing frame shown inFIGS. 3A-3Dhas each of the tracks18formed of substantially the same fiber density (number of fibers per unit area). The fiber crossing frame shown inFIGS. 3A-3Dmay further vary the containment volume of fibers12at distinct test points via compression steps24to provide fiber density variations along the fiber crossing frame of fixed frame20.

One test parameter that represents a quick evaluation of the analysis of the fiber crossing frame of fixed frame20ofFIGS. 3A-Dis an evaluation of the calculated measured directional simulated axonal volume taken along the path of the upper and lower tracks18(as this direction is consistent along the frame20for each crossing test point). The calculated measured directional simulated axonal volume taken along the path of the upper and lower tracks18should equate the known “axonal volume” of the upper and lower tracks18of the phantom10and this calculated amount should remain constant across the fixed frame20ofFIGS. 3A-D. Thus the calculated axonal volume can be used to calibrate a system and validate crossing differentiation of the system.

Fiber Density Frame

FIG. 4is a schematic representation of a phantom10incorporating a number of distinct fixed frames20wherein the upper horizontally extending fixed frame20is formed as a fiber density frame which includes fiber density variations across the fixed frame20, whereby the fibers12/unit area in the fixed frame20are provided at distinct known varied amounts at least at a number of distinct test points across the fixed frame20.

The fixed frame20formed as a fiber density frame includes a series of ten adjacent columns, although other starting numbers are possible, defining a tract22pathway there-through for a track18, with the pathway22interconnecting the adjacent columns. Between adjacent columns a select number of fasciculi16, forming 10% of the original track18fiber number, are diverted/separated from the track18before the track18reaches the next adjacent column. This construction provides an easy way for the fiber density frame to vary the number of fibers12at each column to provide fiber density variations across the fixed frame20. The fixed frame20here is configured to vary the number of fibers12by a fixed fiber amount (e.g., 10%) in adjacent columns Additionally the depth of the fixed frame20at each column includes steps24to vary the containment volume of fibers12along the column to provide for a distinct process of providing fiber density variations. The confinement volume ranges are shown as 1, 1.5, 2 and 3, and these are given as relative volumes relative to the size of the track18with no interstitial water (i.e. only fibers12), with this relative size being1at the most constrained location. The remaining steps are 1.5, 2 and 3 times this volume respectively. Alternative compression steps are possible, e.g., 1.0, 1.24, 1.50, 2.0.

The fixed frame20formed as a fiber density frame provides40distinct test points, with one test point being associated with each confinement volume at each column. The MRI system can be expected to control the simulated axonal volume by fiber amount and confinement amount as well as control and provide reference measurement of the hindered volume by fiber amount and confinement amount. Graphically these test results should appear as linear points across each confinement size of each column. The fiber density frame20provides a calibration for a system and verification of accuracy across a range of fiber densities representing more accurate representation of the range of fiber densities that will be seen in human physiology. It may be advantageous to provide this fiber density frame20in various orientations to validate the system in distinct directions.

As noted above some conventional MRI fiber tracking has difficulty imaging axons much beyond two times the maximum compression volume, which is defined as the volume without interstitial or hindered water.

Hindered and Restricted Water Fixed Frames

FIG. 4is a schematic representation of a phantom10incorporating a number of distinct fixed frames20wherein immediately below the fiber density frame20is a fixed frame20including tracks18in which the hollow tubular fluid14within the fibers12and the interstitial fluid between the fibers12is formed of both water and deuterium oxide, which operates as discussed above.FIG. 4shows a similer set of fixed frames20for calculation of hindered and restricted water extending vertically (behind the fiber density frame20) and end to end (labeled “through plane”). This orthogonal arrangement allows the system to measure hindered and restricted water along three axis. Additionally the hindered and restricted water fixed frames may be duplicated for distinct fiber densities, with only one frame being shown for clarity.

An alternative fixed frame20for analysis of hindered and restricted water is to form two distinct tracks18with similer fiber12paths, and densities except one track18has unfilled (air filled) hollow fibers12with sealed ends, while the other has the fibers12filled with fluid14. In this arrangement the MRI results of the air filled fibers12will only show the interstitial water (or heavy water) signals.

Fiber Crossing Frame

FIG. 4is a schematic representation of a phantom10incorporating a number of distinct fixed frames20wherein immediately below the horizontal hindered and restricted water fixed frame20is a crossing angle fixed frame20substantially as described above, expect this fixed frame20illustrates five crossings at 0 degrees, 15 degrees, 30 degrees 45 degrees and 90 degrees. The construction and operation is substantially similer to that described above and is shown to illustrate the variability of fixed frames20. It may be advantageous to provide this fiber crossing frame20in various orientations to validate the system in distinct directions.

Crossing Density Frame

FIG. 4is a schematic representation of a phantom10incorporating a number of distinct fixed frames20wherein immediately below the crossing angle fixed frame20is a crossing density fixed frame20.

The crossing density frame includes four angle fiber crossings across the fixed frame20, wherein the angle fiber crossings include a plurality of distinct fiber densities. Specifically the crossing density frame can be formed analogous to the crossing angle frame (except the crossing angle is maintained the same at 45 degrees), wherein the crossing density frame includes a lower tract pathway supporting a lower track18within the fixed frame20, an upper tract pathway supporting an upper track18within the fixed frame which is substantially parallel with the lower track18extending horizontally across the fixed frame20as shown and a plurality of intermediate tract pathways between the upper tract pathway and the lower tract pathway each supporting an intermediate track18between the upper track18and the lower track18. Each intermediate track crosses the upper and lower tracks18at the same crossing angles, respectively; however the intermediate tracks have a variety of fiber densities. In addition to the three layers tracks18as shown the crossing frame20may be formed with inter-digitizing or weaving smaller subsets of the fibers12for a more realistic crossing frame, however the three layer structure of the figures is sufficient for illustration of the concept. The densities shown are 5.0, 2.0, 0.5 and 0.2 and are measured relative to the upper and lower tracks18. As with the fixed frame ofFIGS. 3A-D, the calculated measured directional simulated axonal volume taken along the path of the upper and lower tracks18should equate the known “axonal volume” of the upper and lower tracks of the phantom10and this should remain constant across the fixed frame. Again the variance of crossing fiber densities represents a more realistic representation of expected physiology and the phantom10needs to accommodate and validate this aspect of fiber tracking. It may be advantageous to provide this crossing density frame in various orientations to validate the system in distinct directions.

Routing Frame

FIG. 5schematically illustrates a fixed frame20for the phantom10which is formed as a routing frame which includes a plurality of distinct track starting locations at one end thereof shown across the top and labeled1-20. The routing frame20includes a plurality of aligned track ending locations at an opposed end thereof also labeled1-20in a different order from the top location. The routing frame includes tracks18extending from the starting locations to the ending locations of the same number, wherein substantially all of the tracks18end in an ending location that is not aligned with the respective track's starting location so that the tracks18cross each other.

The routing frame provides a validation for tracking the correct fiber path. It may be advantageous to provide this routing frame in various orientations to validate the system in distinct directions. As shown the routing phantom includes tracks of varying fiber densities, specifically a pattern of five track18fiber densities (i.e. the number of fibers per area) repeated four times.

The routing phantom includes extraneous tracks27extending directionally across the routing frame. The tracks27are effectively added noise, although the system could track the noise like any other fiber bundle set. As shown the routing frame further includes distinct areas of crossing fibers or tracts27. The first area has no tracts27, the second area (labeled4) incorporates4noise tracks27(not shown), the third area has10noise tracks27(not shown) while the final area also has10noise tracks27and adds varying fiber densities to the noise tracks27as shown.

Mapping routing accuracy possibly broken down by tract density, for the routing fixed frame will be useful for validating and calibrating the system.

Physiologic Simulation Frame

FIGS. 6Aand B schematically illustrate a fixed frame20for the phantom10which is formed as a physiologic simulation frame and includes a shell simulating a human cranium, simulated eyes32and tracks18simulating known physiologic optical neural tracts from the simulated eyes32. The fixed frame ofFIG. 6illustrates the aspects of the fibers12filled with fluid14, namely that a, simplified, realistic representation of the physiologic fiber tracts can be formed and tested. The physiologic simulation frame may be made as complex as time and money allows, however including conventional and critical fiber crossings of distinct fiber densities should be sufficient for testing. The one addition to the physiologic simulation frame ofFIG. 6which includes tracks18within pathways22for simulating known physiologic optical neural tracts from the simulated eyes32is the inclusion of a pair of segments34in which the frame spreads individual fascicule16to serve as an unmistakable starting point for fiber tracking.

Concurrent Phantom

It should be apparent that each fixed frame20described, is itself an MRI Phantom. However as noted above a plurality of fixed frames20could be used together to calibrate and validate distinct aspects of a system or technology and they may be placed at distinct orientations to simultaneously validate in different orientations.

The phantom10of the present invention provides a tool for validating new algorithms for fiber tracking. Separately the phantom10provides the basis for a periodic checking of an MRI system as part of regimented quality control for validation and calibration of the device. Further, a phantom10according to the present invention may be worn by a patient, referenced herein as a concurrent phantom10, to provide a patient by patient, scan by scan, continuous validation of a machine.FIG. 7illustrates one version of a concurrent phantom10according to the invention, and it includes a strap36to secure the phantom10to the user. The phantom10may be automatically checked by the system and alert the technician to out of alignment results, thus saving a significant number of wasted scans (typically the wasted scans would be those occurring throughout the rest of the day at over $1000/hour of running time). This phantom10is a small version of the full phantom, about the size of a deck of cards (13 cm×6 cm×2 cm), which could be placed over the left ear of the patient during scanning in order to measure fiber12content, providing a baseline for each scan session. Alternatively, it may be built into a cap worn by the patient during the scan, and would contain a fiber track18with controlled confinement, crossing of tracks18, and loss of fibers12(via bundles16), providing a reference to calibrate data across scans.

The concurrent phantom10will give value to the patient. As a hypothetical, in 2016, a patient consult could include a comment such as: “In the eight HDFT MRI scans you have had in your career, each time you wore a blue box on the left side of your head. Inside were millions of hollow textile tubes, smaller than hairs, which have the same shape and density of the axons that make up the cables in your brain. The fact that these tubes are consistent across time gives us confidence that the change we see is in your head and not due the different equipment you were scanned on. The drop to 50% on the arcuate cable after your twelfth IED explosion shows real anatomical loss of the brain cable that supports working memory. After rehabilitation therapy, your scan shows 25 percent recovery of this cable.”

For the war veteran, knowing where the wound is and its extent enables seeking rehabilitation in that they appreciate that there is an anatomical brain loss. Seeing a broken bone in an X-ray helps the patient and physical rehabilitation team to design and complete targeted rehabilitation of the orthopedic injury. Similarly seeing the reduced brain tract provides the patient with resolve to exercise the brain tissue to induce growth and alternative connectivity and recover function. Seeing improvement during rehabilitation results in even greater resolve to continue working on recovery. A stable quantitative referent may be helpful to understand the trauma-induced change in the years following an injury. The ability to quantify reduction and recovery in extent of axonal diffusion will improve the understanding of the nature of brain trauma and recovery.

Kissing, Branching and Funneling Phantoms

The discussion of the fibers12and the construction of fixed frames20above will indicate that the construction of fixed frames20in the form of routing frames that exhibits kissing fiber tracks18(those that have fibers12or fascicules16that approach each other and are concurrent for a segment then diverge without crossing); branching fiber tracks18(fibers12or fascicules16that begin in one bundle or track18and separate in to different tracks18); funneling fiber tracks18(Fibers12or fascicules16that begin as separated and merge to form a single track18); and combinations of these will also be of interest for validation and calibration phantoms10.

The present invention has developed a phantom10for calibrated anisotropic imaging using fluid14filled fibers12that will allow for phantom-calibrated quantification of axonal integrity and axonal loss for detection of diffuse axonal injury (DAI) from TBI. It is critical to be able to quantify and calibrate measurement accuracy in research and medicine. Calibrating a measurement is fundamental to longitudinal cross-instrument combination of those measurements. As of July 2015 there is no such calibration for measures of diffusion anisotropy in brain fiber tracts which exists at any DoD/VA or civilian hospital. The present phantom10, for the first time, provide such technology for white matter tracts, which are the leading organ of Diffuse Axonal Injury (DAI) damage in both animals and man. MRI phantoms have been valued for decades for their ability to evaluate, analyze, and improve the accuracy, precision, and stability of various MRI measures. There is a critical need for phantoms specifically dedicated to diffusion imaging. Although glass and plastic capillaries and a variety of plant and synthetic fibers (e.g., hemp, linen, viscose, rayon, polyamide twine and Dyneema) have been used with varying success to approximate diffusion properties of the human brain, none have been adequately developed for large-scale use in laboratory and clinical research applications. The present phantom10overcomes these deficiencies.

FIGS. 10A-Cillustrates representative scans of an MRI phantom10for calibrated anisotropic imaging according to the invention.FIG. 10Aillustrates a phantom10with a pair of adjacent crossing frames as discussed above in connection withFIGS. 3A-D. Here one of the frames is formed with fibers that were left unfilled while the other is filled with water for illustration purposes.FIG. 10B is an illustration of an MRI T1 structural image of the phantom10ofFIG. 10A, and the lack of fiber tracking/fiber illustration is noticed.FIG. 10B is an illustration of an MRI Diffusion image of the phantom10ofFIG. 10A. The ability of this particular system and algorithm to correctly map crossing fibers can now be quantified and calibrated. Additionally of note is the ability to track fibers at distinct densities. The distinction of the MRI diffusion image of fibers at 1, 2 and 3× maximum constriction volumes is observable.FIGS. 10A-Cdemonstrates some of the applications of the phantoms10of the present invention.

This phantom10is designed to replicate the complex pattern of crossing white matter fibers in the human brain, and will provide ground truth for measurements of compartmentalized water in axons. The phantom10described herein provides precise and repeatedly manufactured axonal diffusion structures to separate and quantify intra-axonal water (termed restricted in the MRI literature) and extra-axonal water (the water between the axons termed hindered water), and free water or isotropic diffusion. The phantom10is composed of hollow fiber, micron-scale textiles manufactured and arranged at controlled crossing and packing densities in two and three dimensions. The phantom10provides ground truth quantification of axonal tract structures, as well as to quantify accuracy and interpretability of diffusion measurements across vendors, instruments, acquisition, and analysis procedures.

The fibers12can be precisely manufactured with controlled packing densities, crossing angles, and curved trajectories, replicating axonal tracts with sub-millimeter precision and micron-level control of axonal diameters. An axon is a tube, 0.5-20 microns in diameter, which may be of long length (a 10 cm axon may have a length-to-diameter ratio of 10,000 to 1). This length-to-diameter ratio is the defining property of the directional axonal imaging that is the basis of diffusion tensor imaging and subsequent technologies. The phantom provides a “ground truth” value for variables used to model diffusion in dMRI, with direct relationship to physiologic anatomy (e.g., tube diameter, tract shape, and interstitial space and fluids). The phantom10allows for quantification measurement error in the pipeline. The textiles are stable, such that they can be disassembled from the phantom10and re-measured to verify maintenance of the water content over years of storage and use.

The phantom10provides a calibration standard across sites, as well as a ground truth structure to advance tract diffusion analysis. The phantom10, in operation, will determine the ability of specific MRI diffusion acquisition parameters (angles and b-values) to quantify known fiber12loss of fibers. The development of the phantom10provides the field with the first ever axon-scale, hindered-water, fiber-crossing phantom10, which will deliver ground truth measurement of compartmentalized diffusion. Although there have been several glass and fiber-oriented diffusion phantoms, none have been able to emulate the hindered water (water in axonal scale tubes) and crossing angles of real brain fibers.

The ground truth simulation reference of phantom10will for the first time provide the field, and DoD imaging centers, with a calibration tool for the measurement of axonal loss, which can be used to improve the quality of fiber tracking data in the research community and hospitals. It will provide the key technology for career-long measurement of military personnel of tract integrity across sites, instruments, and time, which is pivotal to providing standardization and quality control. This aim will enable future DoD/VA requirements specifications for MRI scanner acquisition to include objective specifications that an instrument be able to detect a given percentage of diffuse axonal injury. It will help provide a meaningful, calibrated measurement of TBI-induced brain damage to both the TBI wounded and the clinician teams that treat their wounds.

Universal, Modular Temperature Controlled MRI Phantom for Calibrated Anisotropic and Isotropic Imaging

Following the above descriptions of the MRI phantom10for calibration and validation for anisotropic imaging discussed in connection withFIGS. 2-7 and 10A, the universal, modular, temperature controlled MRI phantom10for calibration and validation for anisotropic and isotropic imaging is shown inFIGS. 11A-Eand comprises an outer insulating shell200configured to be received within an MRI chamber (shown inFIG. 11B); an inner shell210is received within the outer insulating shell200; Fluid conduits220formed in a base222adjacent the inner shell210for receiving temperature controlling fluid or gas cycling there-through; and a series of stacked layers230of frames20containing test points for the MRI phantom, including at least some anisotropic imaging test points in at least one frame20and at least one isotropic imaging test point in at least one frame20.

The outer insulating shell200is preferably a foam insulating layer such as Styrofoam or expanded low density Polyethylene (eLDPE) or similar insulating foams which are MRI compatible. The insulating shell200serves two functions. The first is insulation to assist in maintaining the temperature of the MRI phantom10substantially constant (i.e. +/−8 degrees, although preferably +/−4 degrees, and most preferably +/−2 degrees) throughout a typical calibration testing. The insulation200together with the temperature control elements allow the phantom10ofFIGS. 11A-Eto be operated at other than ambient temperatures (freezing, human body, or other desired temperature) and to be operated at consistent temperatures (+/−8 degrees, and preferably +/−4 degrees and most preferably +/−2 degrees) to prevent a thermal drift in the resulting signals. The phantom10can be operated at any desired temperature, however a fixed temperature around 60-70 degrees F. may be most efficient as this temperature can utilize forced air cooling available in the MRI environment to maintain the desired temperature in use. Maintaining the phantom10at human temperature (98.6 degrees F.) or at freezing (32 degrees F.) is possible and has been proposed for other MRI operations. The Phantom10is designed to provide this utility. The preferred implementation is at body temperature.

Aside from its insulating properties the outer insulating shell200serves the function of fitting the phantom200to the specific MRI coil environment. The outer shell200can be formed specific to a given make and model of MRI, with the remaining elements of the MRI phantom10being consistent across all models. With this specific shell200the operators can easily place the phantom10in a precise location within the coil as will be fixed by the specific outer shell200, as generally shown inFIG. 11B. Assisting in this fitting function the outer shell200includes leveling screws212fixed to inner support frame214upon which the foam of shell200is mounted. This structure will also assist in operation as the placement step becomes simple and easily and consistently accomplished by technicians with minimal effort. The shell200will precisely fit the MRI phantom10in the associated head coil. The phantom10remains universal as the outer shell200is easily formed for each specific head coil shape. The head coil shown inFIG. 11Bis a Siemens 32CH™ brand head coil and represents the smallest head coil space on the market assuring that the phantom10will be easily accommodated in all commercial MRI systems.

The phantom10includes a simulated fat layer206surrounding the inner shell210to simulate the layer of fat or dermal layer surrounding the human head. The fat layer206can be formed as a channel or space filled with oil, such as tree nut oil, to effectively simulate the desired layer. Other materials such as a plastic mesh layer, or other material layer, can be used if it provides the correct MRI signal. The layer206provides added reality to the measured MRI results.

The inner shell210houses the individual testing points of the phantom12within a series of stacked layers230of frames20. The inner shell210may preferably be filled with fluid, generally water or possibly heavy water. The frames20can be of any known phantom or frame design including those as detailed above for anisotropic imaging test points. The frames20may be chambers, or include chambers, such as the isotropic test points of the frames inFIG. 13or possibly where the frame20has fibers18with intersticial fluid differing from the fluid within inner shell210. The universal phantom10preferably includes at least some anisotropic imaging test points (shown inFIG. 11Cin the upper layer230) in at least one frame20and at least one isotropic imaging test point in at least one frame20(shown in the lower layer230inFIG. 11C, as detailed below). Only two layers230are shown inFIG. 11Cfor clarity but as schematically illustrated inFIG. 11Aseveral more layers can be accommodated within the phantom10as desired.

Temperature Control

As noted above the temperature control elements together with the insulation200allow the phantom10ofFIGS. 11A-Eto be operated at other than ambient temperatures (freezing, human body, or other desired temperature) and to be operated at consistent temperatures (+/−8 degrees, and preferably +/−4 degrees and most preferably +/−2 degrees) to prevent a thermal drift in the resulting signals. The temperature control elements comprise fluid conduits220formed in a base222adjacent the inner shell210for receiving temperature controlling fluid or gas cycling there-through. Ports224in base222allow the fluid conduits220to be coupled to a source of heating or cooling fluid or gas. When the phantom10is not in operation it can be coupled to a separate source of temperature controlling fluid or gas (i.e., a heater and pump—not shown) which is part of a temperature maintaining docking or storage station. In operation the insulation200can maintain the phantom substantially at a constant temperature throughout the calibration step in the MRI. It is possible that within the MRI environment the ports224can be coupled to the forced air source commonly found in such environments if the air from the source is closer to the desired constant temperature of the phantom than ambient temperatures. Further, active heating of the fluid during scanning is an alternative where the heating unit/pump exists in the MR scanning room, fluid transferred through tubes that run through an MR Scanner room waveguide, and connect directly to the phantom10in the scanner through couplers in the base222. This heating apparatus can also exist in the MR Scanner room itself so long as the mechanics are kept out of the high gauss fields are contained within a Faraday cage (similar in concept to the tech used in our MRI video patent).

Additionally the temperature control may further include channels extending up into the inner shell210(or around the shell210) of the phantom10. Temperature controlling water or air (or other liquid or gas) channels could be extended into sub-channels introduced into the shell itself and/or other structures such as through layer230elements such as through the supporting posts232of the layers230in order to aid in heat transfer and stability of temperature. The use of effective insulation in outer shell200minimizes the need for additional channels in the inner shell210

FIG. 12schematically illustrates an anisotropic imaging layer230formed as a series of crossing frames20the details of which are generally discussed above. The layer230includes stacking elements or posts232to facilitate the stacking and mounting of layers230. Layer230includes fiducials234to convey at least the location and orientation of the layer230to the MRI. Fiducial elements234are any marker that is visible to the MRI that can be used to register the layer230. It is noted that the outer layer200with leveling screws212minimize the need for registration fiducials234as the layers230will be consistently placed with each testing. The fiducials234may be a geometric shape as shown on the top, or a readable label as shown at the bottom which can convey both information regarding where the layer230is (i.e. registration information) and specifically of what the layer230consists (information for the MRI analysis). Fiducials234on the two sides of the layer230represent a coded fiducial to convey information (more than registration information) wherein each square (or cube) of this fiducial234is covered with a material of a known MRI signal such that the collection of these forms an MRI compatible coded information package, like an MRI compatible bar code. In this manner the fiducials234can signal both position and substance to the MRI system. The fiducials234for the layer230can also be formed as the sides or edges of other structures such as posts232and frames20.

FIG. 12Bschematically illustrates an anisotropic imaging layer230formed as a series of density frames20the details of which are generally discussed above. The layer230includes posts232to facilitate the stacking and mounting as well as fiducials234to convey at least the registration information for the layer230to the MRI as discussed above.

FIG. 12Cis a top plan view of an anisotropic imaging layer230formed as a series of crossing and density frames20the details of which are generally discussed above. The layer230includes posts232to facilitate the stacking and mounting as well as fiducials234to convey at least the location of the layer230to the MRI as discussed above.FIG. 12Dis a perspective view of an anisotropic imaging layer230ofFIG. 12C.

FIG. 13is a sectional perspective view of a frame layer230for isotropic test points for the universal, modular, temperature controlled MRI phantom10ofFIG. 11B. The layer230is formed as an array of frames20in the form of rectangular chambers that are configured to receive liquids, gels or the like of known and different MRI signatures. The use of an array of distinct MRI signal materials is a known isotropic test phantom. The layer230ofFIG. 13further includes a conical top240with sealing member242. The conical top240to the rectangular test point chamber allows the chamber to be filled with minimal air spaces that could interfere with the testing and any residual minimal air bubble is hopefully located out of the test area. The sealing member242can also serve as a fiducial and can be encoded to further convey what is in the associated chamber or frame20.FIG. 13also illustrates another common feature of the phantom10which is that the test areas are preferably rectangular as opposed to spherical as used extensively in the prior art. The rectangular test area is believed to better associate with the voxel.

It is apparent that many variations to the present invention may be made without departing from the spirit and scope of the invention. The present invention is defined by the appended claims and equivalents thereto.