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WO2024062354A1 - Fantôme d'imagerie anthropomorphique du cerveau modélisé par dépôt fondu ayant des parois submillimétriques pour des études multicompartimentales et morpho-fonctionnelles, son procédé de fabrication et moyen associé - Google Patents

Fantôme d'imagerie anthropomorphique du cerveau modélisé par dépôt fondu ayant des parois submillimétriques pour des études multicompartimentales et morpho-fonctionnelles, son procédé de fabrication et moyen associé Download PDF

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Publication number
WO2024062354A1
WO2024062354A1 PCT/IB2023/059179 IB2023059179W WO2024062354A1 WO 2024062354 A1 WO2024062354 A1 WO 2024062354A1 IB 2023059179 W IB2023059179 W IB 2023059179W WO 2024062354 A1 WO2024062354 A1 WO 2024062354A1
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Prior art keywords
phantom
teeth
wheel
brain
circle
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PCT/IB2023/059179
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English (en)
Inventor
Bruno Alfano
Mario MAGLIULO
Maria Agnese PIROZZI
Anna Prinster
Mario QUARANTELLI
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Human Shape Technologies Srl
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Human Shape Technologies Srl
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B6/00—Apparatus or devices for radiation diagnosis; Apparatus or devices for radiation diagnosis combined with radiation therapy equipment
    • A61B6/58—Testing, adjusting or calibrating thereof
    • A61B6/582—Calibration
    • A61B6/583—Calibration using calibration phantoms
    • G—PHYSICS
    • G09—EDUCATION; CRYPTOGRAPHY; DISPLAY; ADVERTISING; SEALS
    • G09B—EDUCATIONAL OR DEMONSTRATION APPLIANCES; APPLIANCES FOR TEACHING, OR COMMUNICATING WITH, THE BLIND, DEAF OR MUTE; MODELS; PLANETARIA; GLOBES; MAPS; DIAGRAMS
    • G09B23/00—Models for scientific, medical, or mathematical purposes, e.g. full-sized devices for demonstration purposes
    • G09B23/28—Models for scientific, medical, or mathematical purposes, e.g. full-sized devices for demonstration purposes for medicine
    • G09B23/286—Models for scientific, medical, or mathematical purposes, e.g. full-sized devices for demonstration purposes for medicine for scanning or photography techniques, e.g. X-rays, ultrasonics

Definitions

  • the present invention relates to an anthropomorphic imaging phantom of the brain modeled with molten deposition having sub-millimeter walls for multi-compartmental and morpho- functional studies , the process for making it , and the related means .
  • the invention relates to the definition, optimi zation and automation of a production process of an anthropomorphic phantom forming a faithful replica of three brain compartments , those of gray matter (GM) , white matter (WM) and striatum or basal-ganglia, made in a single procedure , and with sub-millimeter wall thickness features , which make it suitable for morpho- functional imaging studies .
  • Said anthropomorphic phantom is made of thermoplastic material by means of advanced modeling and additive production techniques with molten filament deposition and is made completely impermeable with an innovative technique , neces sary to ensure the perfect seal of the phantom when it is f illed with liquids .
  • Thewaterproof ing is based on a solution, capable of penetrating the micro-holes of the 3D printed matter, and solidi fying, with which the various compartments of the phantom are filled separately, thus obtaining the impregnation of the walls .
  • the phantom is then placed on an innovative rotation system which, making the phantom itsel f take a continuum of orientations , allows the polymer solution which has not penetrated the 3D printed matter to flow on all the inner walls , until the complete drying of the solution .
  • Phantoms can be geometric or anthropomorphic . Geometric phantoms are simpler and are used to measure speci fic features such as spatial resolution and image homogeneity .
  • Anthropomorphic phantom otherwise referred to as " anatomical , " means an obj ect capable of faithfully simulating the anatomical features of a particular organ of the human body .
  • Anthropomorphic phantoms are advanced obj ects of characteri zation and testing for clinical imaging equipment , used to evaluate the performance thereof in diagnosis and therapy contexts . Moreover, phantoms are used to develop techniques for performing diagnostic exams in total safety, providing results very similar to those obtained on real patients . These phantoms are generally used to quanti fy the error made in the evaluation, through diagnostic studies , of the measurements of chemical-physical parameters on a patient (such as the concentration of radioisotopes or volumetric measurements ) , or to correct defects in images (such as partial volume ef fect ) .
  • an anthropomorphic phantom is designed to be used only with a certain category of imaging instrumentation, for example , or for Emission Tomography, or for both Positron Emission Tomography ( PET ) and Single Photon Emission Tomography (SPECT ) ; or for Magnetic Resonance Imaging (MRI) or Computerized Tomography (CT) .
  • a certain category of imaging instrumentation for example , or for Emission Tomography, or for both Positron Emission Tomography ( PET ) and Single Photon Emission Tomography (SPECT ) ; or for Magnetic Resonance Imaging (MRI) or Computerized Tomography (CT) .
  • the brain phantoms which emulate the external anatomy of the brain have a reduced depth of the grooves, or recreate only the surface shape, obtaining it by means of molds.
  • such phantoms fail to faithfully represent the anatomy thereof and the variety of brain tissues. Still others are made in several parts which must be then assembled, or in layers a few millimeters thick, to the detriment of the anatomical fidelity and level of detail of the structures made.
  • CT/MRI radiology
  • geometric phantoms are generally used for quality control.
  • CT/MRI radiology
  • anthropomorphic commercial phantoms which approximate only the anatomy of an entire brain (e.g., Hoffman's phantom) , in the gray matter (GM) and white matter (WM) compartments; or only the basal-ganglia, more specifically the striatum, inside a container casing of geometry similar to the brain (e.g., Alderson's phantom) .
  • Hoffman's phantom consists of a cylindrical container filled with a series of circular plates in which trans-axial sections are cut out following the shape of the GM and alternatively of the WM + GM. Therefore, the volume corresponding to the GM is completely empty, while that corresponding to the WM is only partially empty, as it also contains the plates in which the GM+WM profile is cut.
  • the full empty ratio at the WM is made proportionally to the concentration ratio of [ 18 F]FDG (the radiopharmaceutical used in PET studies of brain metabolism) between WM and GM in a normal subject, in which this ratio is assumed to be equal to M.
  • the workflow developed and optimi zed for the creation of an anthropomorphic phantom in thermoplastic material with multiple compartments , made in a single procedure and with submillimeter wall thickness features includes the following steps :
  • fig . 1 shows the core of the rotation system on which the phantom according to the invention is placed, in the waterproofing step and which, by making the phantom take a continuum of orientations , solves the problem of flowing the non-penetrated waterproofing solution on all the inner walls thereof , unti l the complete drying of the solution;
  • fig . 2 is a perspective view of the rotation system in fig . 1 also comprising three other elements : a fixed toothed wheel , a movable toothed wheel and a counterweight ; fig .
  • fig. 3 shows the complete rotation system, with the housing for the phantom integral with the inner circle ;
  • fig . 4 shows the complete traj ectory, seen from above , of a unit vector positioned on the center of the inner circle where the traj ectory part in the lower part of the ball traveled by the traj ectory is highlighted in light grey;
  • fig. 5 shows the trajectory corresponding to the first 5 revolutions of the outer circle, showing that, apart from the intersections, the spatially close points in the trajectory are temporally spaced, which ensures a homogeneous distribution of the polymer inside the phantom;
  • fig. 6 is a side elevation picture of the anthropomorphic phantom at the end of the above procedure .
  • the invention serves to simulate the biophysical and pathophysiological conditions of human brain tissues in clinical imaging. This aims to improve the interpretation of patient brain studies by means of nuclear medicine methods such as PET and SPECT. Moreover, given the high resolution thereof, obtained by virtue of a sophisticated 3D printing technique, it is the only one suitable for characterizing hybrid diagnostic scanners with MRI and CT, i.e., PET-MRI, PET-CT, and SPECT-CT hybrid scanners.
  • the suggested technological solution represents a significant advancement as compared to the prior art.
  • the invention brings a significant advantage with respect to the currently available phantoms, because it overcomes a number of limitations.
  • the suggested technological solution allows obtaining a series of independent compartments, despite the same being anatomically interconnected, which can be filled with different (and not necessarily fixed) concentrations of radio-composites for Nuclear Medicine exams ( PET or SPECT ) , contrast media for CT exams , or solutions mimicking the behavior of brain tissues during an MRI .
  • the reproduced compartments which concern both gray matter (GM) , white matter (WM) , and the striatum of a normal subj ect , are defined by a thin separation wall characteri zed by a sub-millimeter thickness , which can be made in additive manufacturing by means of molten filament deposition techniques .
  • the additive manufacturing, optimi zed according to the process carried out by virtue of the layer-by-layer production, allows making a faithful replica o f the anatomical shapes , albeit as complex as those of the brain compartments , in a single and closed obj ect , but with hollow compartments which can then be filled with di f ferent ( and not necessarily fixed) concentrations depending on the simulation to be carried out .
  • Segmentation obtained by means of brain tissue volume recognition software developed in-house allows the accurate selection in MRI images of voxels ( a voxel is the three-dimensional counterpart of the two- dimensional pixel ) of di f ferent brain tissues , including GM, WM and subcortical gray matter structures (also referred to as basal-ganglia ) .
  • the software for recognizing the volumes of interest which is already the result of previous research work, is presented in the works (Alfano B. et al. , Magn Reson Med. 1997; 37(l) :84-93. doi : 10.1002/mrm.1910370113 ; Alfano B. et al. , Med Image Anal.
  • the definition of voxel surfaces at the interface between the different compartments of the phantom is instead part of the present inventive activity and is the subject of the present invention.
  • the individual voxel surfaces at the interface of the compartments of interest are obtained from the volumes edited in point 1 by selecting the voxels (from the outside to the inside) which share vertices, edges and faces.
  • the automated procedure developed allows obtaining a correct vector modeling file (in Standard Tessellation Language (STL) format) from the voxels, on which only a few subsequent finishes must be made (see point 3) .
  • STL Standard Tessellation Language
  • the voxel surface was designed according to this criterion because it is the only one which ensures the extraction of a "non-perf orated" STL surface connected in all the points thereof and with a predefined thickness. Moreover, as a last check, the extraction routine verifies that the final thickened surface of the phantom is unique and closed.
  • the invention allows making a single interface surface between multiple compartments, which is much more advantageous and simpler than the procedures known in the prior art which instead include the definition of multiple surfaces (one per compartment) from the volumes which must be then thickened, as necessary. After complicated Boolean joints, the surfaces between adjacent compartments would thus result in a thickness which is twice that of the single surface.
  • the invention instead allows making, in a single automatic step, a single surface with a constant thickness, and not different surfaces per compartment which merge.
  • the segmented volumes of GM, WM and Striatum have not undergone further smoothing, but only an interpolation to the nearest neighbor to create an isotropic voxel (depending on the case, it can be made in the range from 0.50 mm to 0.75 mm) suitable for the subsequent extraction of sub-millimeter surfaces in voxels (see point 2) .
  • the suitable thickness has been defined to be able to be materialized by means of molten filament deposition with optimized pathways (see point 3) .
  • a polygonal mesh in STL format is extracted using the Marching Cubes algorithm (https : //dl . a cm. org/ doi/10.1145/37401 .37422 ) , a high-resolution 3D surface construction algorithm.
  • Such an algorithm includes setting a smoothing by means of a windowed sync function approximated by means of a polynomial of a chosen degree equal to 10 for an optimal smoothing of the 3D model ( elimination of the groove introduced by the slice thickness of the processed images ) .
  • a polygonal mesh decimation parameter is optimi zed to lighten the 3D model from a computational point of view, appropriately reducing the number of faces forming the mesh surface .
  • the decimation works respecting the features of the model .
  • the mesh faces on a fairly uni form plane are reduced more sensitively s compared to those def ining irregular and more complex shapes (such as GM convolutions and WM fibers ) . Therefore , a scrupulous decimation factor, chosen for optimi zation equal to 0 . 1 to ensure a 10% reduction in the number of triangles in the mesh with respect to the maximum resolution, still preserves the geometry and shapes , saving a great deal in the weight of the model file in STL format .
  • the present invention makes a fair compromise to eliminate the unsightly ef fect of voxeli zation on the surface (which could at the same time complicate the additive manufacturing) , while maintaining a faithful representation o f the anatomy of brain tissues .
  • a di f ferent setting of the 3D modeling such a complex phantom model could not be elaborated for the definition of the deposition pathways of molten material ( see point 3 ) of the next production step ) .
  • the STL file is further finished with the addition of threaded j oints suitably designed for screwing caps to close the phantom .
  • the resulting mesh is lastly corrected for any errors which may be generated on the tube area during handling .
  • Optimi zation of the slicing and additive printing pathways to obtain a dense and thus waterproof texture are particularly useful.
  • the thickness of the layer for additive production (below referred to as printing) and advanced deposition parameters of the molten filament were optimi zed to obtain a dense and waterproof printing texture .
  • a layer thickness is fixed which ensures that at least two j uxtaposed lines of material are deposited for the vertical walls and more than one layer for the hori zontal and oblique walls , so as to optimally seal the printing texture .
  • advanced production parameters were selected to be appropriately set to obtain the desired features in the printing texture , such as strengthening of the vertical walls , thickening ( as much as possible ) of the textures deposited in the filling of the hori zontal walls , to ensure the continuity of the printed walls and minimi ze the presence of small holes and cavities in the walls themselves .
  • the waterproofing technique normally used for 3D prints with molten filament deposition consists of exposing the print made to the vapors of a solvent suitable for the material used, for calibrated time intervals ; for example , for ABS prints acetone vapors are used .
  • the interaction time is determined so that only the most superficial part of the printed matter dissolves , filling the micro-holes which are produced during the printing, but without deforming or even perforating the printed matter .
  • Such a technique is absolutely not usable for a phantom with the features of that suggested herein .
  • the solvent vapors should interact for the same time with all the inner and outer walls of the phantom, which is impossible due to the complexity of the shape of the phantom itsel f .
  • a technique of waterproofing the phantom has been developed . It is based on a substance (which in the preferred embodiment is a polymeric solution, capable of penetrating the micro-holes of the 3D printed matter, with which the various compartments of the phantom are filled separately, thus obtaining the impregnation of the walls .
  • the phantom is then placed on a particular rotation system, described hereinafter, which makes the phantom take a continuum of orientations , causing the non-penetrated solution to flow on all the inner walls thereof until the complete drying of the solution . ( The treatment can be repeated several times ) .
  • the rotation system designed ad hoc, is shown in Figure 1 .
  • the outermost circle can rotate about the hori zontal axis Ao and is connected to the output of a gear motor M.
  • the innermost circle can rotate about the axis Ar which is integral with the outermost circle ; the inner circle can thus take any orientation in space .
  • Figure 2 also shows three other elements of the rotation system : the fixed toothed wheel Rf; the movable toothed wheel Rm and the counterweight Cp .
  • the first toothed wheel Rf is integral with the fixed structure of the system
  • the second toothed wheel Rm and the counterweight Cp are pivoted, preferably by means of ball bearings, in the outer circle and are integral with the inner circle.
  • the toothed wheels have teeth 45° inwards so as to form a gear. Since the movable wheel is always at the same distance from the rotation axis of the outer circle, the teeth thereof are always meshed with those of the fixed wheel and therefore, when the outer circle rotates, it produces a corresponding rotation of the inner circle.
  • the rotation angle of the inner circle about Ar is equal to the rotation angle of the outer circle about Ao multiplied by the ratio of the number of teeth of the fixed wheel to the number of teeth of the movable wheel.
  • Ae - x*2n Ai - y*2n, x and y being integers.
  • Fig. 3 shows the complete rotation system with the housing for the phantom integral with the inner circle .
  • the traj ectory described by the inner circle wil l return to the starting point after the outer circle has made a number of revolutions equal to the number of teeth of the movable wheel and the inner circle a number of revolutions equal to the number of teeth of the fixed wheel .
  • Rf has 79 teeth and Rm 67 teeth, whereby the rotation system will return to the starting position when the outer circle has made 67 turns and the inner one 79 .
  • Figure 4 shows the complete traj ectory, seen from above , of a unit vector positioned on the center of the inner circle (the traj ectory part in the lower part of the ball travelled by the traj ectory is highlighted in light grey) .
  • Figure 5 shows the traj ectory corresponding to the first 5 revolutions of the outer circle , showing that apart from the intersections , the spatially close points in the traj ectory are temporally spaced, which ensures a homogeneous distribution of the polymer inside the phantom .

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Abstract

Selon la présente invention, un fantôme anthropomorphique formant une réplique fidèle de trois compartiments cérébraux, ceux de la matière grise (MG), de la matière blanche (MB) et du striatum ou des ganglions de la base, est constitué d'un matériau thermoplastique en une seule procédure au moyen de techniques de modélisation avancées et d'une production additive avec un dépôt de filament fondu ayant des caractéristiques d'épaisseur de paroi submillimétrique, ce qui le rend approprié pour des études d'imagerie morpho-fonctionnelle. Ledit fantôme est étanche à l'eau pour assurer son étanchéité parfaite lorsqu'il est rempli de liquides, ce qui permet de remplir séparément les divers compartiments du fantôme avec une solution qui est apte à pénétrer dans les micro-trous de la matière imprimée en 3D et à se solidifier. Il est prévu un système de rotation innovant qui, permettant au fantôme lui-même de prendre un continuum d'orientations, permet à la solution polymère qui n'a pas pénétré dans la matière imprimée en 3D de s'écouler contre toutes les parois internes, jusqu'au séchage complet de la solution.
PCT/IB2023/059179 2022-09-21 2023-09-15 Fantôme d'imagerie anthropomorphique du cerveau modélisé par dépôt fondu ayant des parois submillimétriques pour des études multicompartimentales et morpho-fonctionnelles, son procédé de fabrication et moyen associé Ceased WO2024062354A1 (fr)

Applications Claiming Priority (2)

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IT102022000019383A IT202200019383A1 (it) 2022-09-21 2022-09-21 Fantoccio antropomorfo di imaging del cervello modellato a deposizione fusa con pareti submillimetriche per studi multicompartimentali e morfo-funzionali, processo per la sua realizzazione e mezzi relativi.
IT102022000019383 2022-09-21

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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20180267127A1 (en) * 2015-02-23 2018-09-20 Siemens Healthcare Gmbh Three-dimensional printing of phantoms for medical imaging

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ITRM20020477A1 (it) 2002-09-25 2004-03-26 Consiglio Nazionale Ricerche Procedimento per la realizzazione di un fantoccio stereolitografato biomorfo, multicompartimentale e per esami multianalitici, e relativo dispositivo.

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20180267127A1 (en) * 2015-02-23 2018-09-20 Siemens Healthcare Gmbh Three-dimensional printing of phantoms for medical imaging

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
JONASSON L S ET AL: "Simulating effects of brain atrophy in longitudinal PET imaging with an anthropomorphic brain phantom", PHYSICS IN MEDICINE AND BIOLOGY, INSTITUTE OF PHYSICS PUBLISHING, BRISTOL GB, vol. 62, no. 13, 31 May 2017 (2017-05-31), pages 5213 - 5227, XP020317586, ISSN: 0031-9155, [retrieved on 20170531], DOI: 10.1088/1361-6560/AA6E1B *
WILSON TYLER ET AL: "SPECT simulation of a digital anthropomorphic brain phantom", PROGRESS IN BIOMEDICAL OPTICS AND IMAGING, SPIE - INTERNATIONAL SOCIETY FOR OPTICAL ENGINEERING, BELLINGHAM, WA, US, vol. 12031, 4 April 2022 (2022-04-04), pages 120313U - 120313U, XP060155775, ISSN: 1605-7422, ISBN: 978-1-5106-0027-0, DOI: 10.1117/12.2613282 *

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