1、BSI Standards PublicationPD ISO/TR 16379:2014Tissue-engineered medicalproducts Evaluation ofanisotropic structure ofarticular cartilage using DT(Diffusion Tensor)-MR ImagingPD ISO/TR 16379:2014 PUBLISHED DOCUMENTNational forewordThis Published Document is the UK implementation of ISO/TR 16379:2014.T
2、he UK participation in its preparation was entrusted to Technical Committee RGM/1, Regenerative medicine.A list of organizations represented on this committee can be obtained on request to its secretary.This publication does not purport to include all the necessary provisions of a contract. Users ar
3、e responsible for its correct application. The British Standards Institution 2014.Published by BSI Standards Limited 2014ISBN 978 0 580 82564 4ICS 11.040.40Compliance with a British Standard cannot confer immunity from legal obligations.This Published Document was published under the authority of th
4、e Standards Policy and Strategy Committee on 31 May 2014.Amendments/corrigenda issued since publicationDate T e x t a f f e c t e dPD ISO/TR 16379:2014 ISO 2014Tissue-engineered medical products Evaluation of anisotropic structure of articular cartilage using DT (Diffusion Tensor)-MR ImagingProduits
5、 mdicaux base de tissus valuation de la structure anisotrope du cartilage articulaire en utilisant limagerie en tenseur de diffusion (IRM-TD)TECHNICAL REPORTISO/TR16379First edition2014-03-01Reference numberISO/TR 16379:2014(E)PD ISO/TR 16379:2014ISO/TR 16379:2014(E)ii ISO 2014 All rights reservedCO
6、PYRIGHT PROTECTED DOCUMENT ISO 2014All rights reserved. Unless otherwise specified, no part of this publication may be reproduced or utilized otherwise in any form or by any means, electronic or mechanical, including photocopying, or posting on the internet or an intranet, without prior written perm
7、ission. Permission can be requested from either ISO at the address below or ISOs member body in the country of the requester.ISO copyright officeCase postale 56 CH-1211 Geneva 20Tel. + 41 22 749 01 11Fax + 41 22 749 09 47E-mail copyrightiso.orgWeb www.iso.orgPublished in SwitzerlandPD ISO/TR 16379:2
8、014ISO/TR 16379:2014(E) ISO 2014 All rights reserved iiiContents PageForeword ivIntroduction v1 Scope . 12 Terms and definitions . 13 Principle 34 Diffusion tensor magnetic resonance imaging (DT-MRI) data observation in articular cartilage 34.1 DT-MRI measurement process 34.2 Notes on setting of DT-
9、MRI imaging parameters for articular cartilage . 44.3 Measurement indices for structural evaluation of articular cartilage by DT-MRI 5Annex A (informative) Measurement Results 10Bibliography .23PD ISO/TR 16379:2014ISO/TR 16379:2014(E)ForewordISO (the International Organization for Standardization) i
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16、ants for Surgery, Subcommittee SC 7, Tissue-engineered Medical Products.iv ISO 2014 All rights reservedPD ISO/TR 16379:2014ISO/TR 16379:2014(E)IntroductionStructural evaluation of articular cartilage with conventional diagnostic technologies is challenging, and Nihon University has developed technol
17、ogies (see Reference 1) and collected relevant data for in vivo evaluation of articular cartilage structure by means of diffusion tensor magnetic resonance imaging (DT-MRI) using 1,5 Tesla or 3 Tesla MRI equipment employed for treatment in hospital settings. These data are released in this Technical
18、 Report prepared for reference in treatment settings.This work is part of “Development of Cartilage Observation and Evaluation Technologies for Regenerative Medicine Processes”, an activity managed by the University under “Development of Evaluation Technology for Early Introduction of Regenerative M
19、edicine”, a project contracted by the New Energy and Industrial Technology Development Organization (NEDO) to the National Institute of Advanced Industrial Science and Technology (AIST) and its Technology Research Association of Medical Welfare Apparatus. ISO 2014 All rights reserved vPD ISO/TR 1637
20、9:2014PD ISO/TR 16379:2014Tissue-engineered medical products Evaluation of anisotropic structure of articular cartilage using DT (Diffusion Tensor)-MR Imaging1 ScopeThis Technical Report has been prepared for evaluation of therapeutic courses for articular cartilage disease and summarizes results fr
21、om structural evaluation of knee joint cartilage by diffusion tensor imaging, an MRI applied technology allowing non-invasive observation of soft tissue morphology in vivo.This Technical Report is intended for use in areas such as regenerative medicine for knee joint cartilage disease.After in vivo
22、transplant of cartilage cells or tissue as a regenerative treatment, longitudinal diagnosis is needed to assess regeneration as articular cartilage, but arthroscopes used primarily for this purpose are invasive and also do not allow evaluation of structure by simple observation of surfacial characte
23、ristics. Radiography and CT do not visualize articular cartilage and also entail the problem of exposure. Collagen fibres, the primary component of articular cartilage, have a surfacial layer parallel to the articular surface to serve a lubricating function for the articular surface, a middle layer
24、with a randomized structure to distribute loads, and deep layers oriented vertically to support loads. The anisotropy of this three-layer structure is a characteristic feature of hyaline cartilage structures and a mechanism demonstrating a lubricating function for articular cartilage. We can then as
25、k whether articular cartilage can be assessed by evaluating the anisotropy of collagen.MRI techniques allow non-invasive visualization of soft tissue form and function in vivo, and DT-MRI conveys the direction of water molecule motion. In fibrous tissues, the direction of water molecule motion is re
26、stricted to the direction of fibre orientation; consequently, the direction of water molecule motion matches that of fibre orientation. The use of DT-MRI therefore does allow evaluation of collagen fibre orientation and anisotropy in articular cartilage.DT-MRI is thus used to observe articular carti
27、lage anisotropy data for use as standardized data in longitudinal diagnosis following transplant of articular cartilage as a regenerative treatment.2 Terms and definitionsFor the purposes of this document, the following terms and definitions apply.2.1diffusion tensorDTtensor expressing the orientati
28、on and magnitude of diffused proton signals2.2sequenceprotocol for performance of MRI2.3spin-echo echo-planar imagingSE-EPImethod of high-speed imaging in which gradient fields are flipped continuously at high speed to produce echoes continuously by means of a spin-echo pulse sequenceTECHNICAL REPOR
29、T ISO/TR 16379:2014(E) ISO 2014 All rights reserved 1PD ISO/TR 16379:2014ISO/TR 16379:2014(E)2.4field of viewFOVwidth and height of an imaged region (expressed in cm or mm)2.5matrixpixel resolution for acquisition of MR signals in a field of view2.6echo timeTEtime after RF pulse application until an
30、 echo is producedSOURCE: JIS K 36112.7radio frequency pulseRF pulseshort duration, high-frequency electromagnetic wave in pulse formSOURCE: JIS K 36112.8repetition timeTRtime interval for repetition of the basic unit of magnetic resonance pulse sequencesSOURCE: JIS K 36112.9slice thicknessthickness
31、of the imaging plane2.10number of averagesNAnumber of times an identical MR signal is repeated2.11b valuemaximum value of the parameter indicating level of diffusion weighting2.12motion probing gradientMPGgradient field applied to detect diffusion2.13parallel imaginghigh-speed imaging method making
32、use of the difference in sensitivities provided by multiple coils2.14fractional anisotropyFAnumber indicating level of structural anisotropy2.15mean diffusivityMDmean of diffusion coefficients along the three primary axes of a diffusion tensor2 ISO 2014 All rights reservedPD ISO/TR 16379:2014ISO/TR
33、16379:2014(E)2.16signal-to-noise ratioSNRvalue expressing the proportion of signal to noise; greater values indicate higher image quality2.17voxelthree-dimensional cuboid representing the minimum unit comprising a three-dimensional image3 PrincipleIn the regeneration medicine for artificial cartilag
34、e, it is important to evaluate whether the implanted tissues regenerate as an artificial cartilage with time. However, an arthroscope is invasive and only monitors the surface texture of articular cartilage. X-ray and CT cannot project the cartilage tissue and have an exposure problem.An articular c
35、artilage has anisotropy by differential orientation of collagen fibra to exert a lubrication property as a joint. In the superficial layer, collagen fibra is oriented to parallel on joint surface. Next, in the middle layer, collagen fibra was in random for distribution of loading and oriented vertic
36、ally in deep layer. Such three-layer structure is a feature of articular cartilage, which is based on the biomechanical property of articular cartilage. Thus, it is possible to evaluate whether or not the articular cartilage by observation of the anisotropy structure.In DT-MRI, in MRI techniques, it
37、 is possible to know the direction of proton movement. In fibrotic tissues, as the direction of water molecule movement is limited along the orientation of collagen fibro, the fibro direction is consistent with the direction of proton movement. Therefore, the direction of collagen structure can be e
38、valuated with DT-MRI.In this draft, DT-MRI data obtained from healthy male by using several MR devices shows for use as reference data to evaluate the process after regenerate treatment of articular cartilage.4 Diffusion tensor magnetic resonance imaging (DT-MRI) data observation in articular cartil
39、age4.1 DT-MRI measurement processThe process shown in the flowchart in Figure 1 is used for acquisition, measurement, and observation of data to evaluate articular cartilage structure. This Technical Report envisions that different models of MRI equipment are used in different hospital facilities, a
40、nd thus observational data are shown for three types of MRI apparatus produced by different manufacturers. Table 1 presents the MRI apparatus, signal-receiving coils, and imaging parameters used in observation. ISO 2014 All rights reserved 3PD ISO/TR 16379:2014ISO/TR 16379:2014(E)Figure 1 DT-MRI dat
41、a measurement processTable 1 MRI apparatus, signal-receiving coils, and imaging parameters used in DT-MRIImaging facilityKyoto University Institute for Frontier Medical SciencesNihon University School of Dentistry at Matsudo HospitalHiroshima University HospitalApparatus (Manufacturer)SONATA 1,5T (S
42、iemens)Achieva 1,5T (Philips)Signa Excite 3T (General Electric)Signal-receiving coil 4 ch flex array 8 ch sense knee Lower extremitySequence SE-EPI SE-EPI SE-EPIFOV mm 192 192 150 150 128 128Matrix 192 192 144 142 128 128TR ms 2 200 2 200 2 200TE ms 70 68 68Slice thickness mm 3 5 5Number of averages
43、 24 20 12b-value 600 600 400No. MPG axes 6 6 6,15Parallel imaging GRAPPAaSENSEbn/aImage slice Sagittal plane Sagittal plane Sagittal planePixels 384 384 400 400 256 256aGeneralized rapid acquisition with partially parallel acquisition.bSensitivity encoding.4.2 Notes on setting of DT-MRI imaging para
44、meters for articular cartilage4.2.1 Imaging resolutionThe resolution at which MR signals are acquired corresponds to a voxel size determined by matrix and slice thickness. Larger voxel sizes correspond to higher SNR, which also increases data reliability. Conversely, smaller voxel sizes increase res
45、olution but decreased SNR of MR signals, which decreases data reliability.4 ISO 2014 All rights reservedPD ISO/TR 16379:2014ISO/TR 16379:2014(E)Because articular cartilage has a three-layer structure with differing collagen fibre orientations (see Reference 2), the matrix and slice thickness paramet
46、ers used for this Technical Report were selected to allow acquisition of three-layer data.4.2.2 Repetition timeLonger TR increases the number of slices in an image but lengthens imaging time. The parameter in this Technical Report was selected based on Reference 1.4.2.3 Number of averagesA greater n
47、umber of signal averages raises SNR and also increases data reliability but lengthens imaging time. The parameter in this Technical Report was selected based on Reference 1.4.2.4 b-valueHigher b-values lengthen TE, which might lead to under-representation of diffusivity. Conversely, lower b-values c
48、an lead to over representation of diffusivity, and this parameter shall be set with consideration for the imaging target. The parameter in this Technical Report was selected based on Reference 1.4.2.5 Motion probing gradient (MPG)MPG shall be applied in a minimum of six directions to determine diffu
49、sion tensors. As MPG is applied to more axes, more complex structures can be analysed, but imaging time lengthens. But for application of MPG to equal numbers of axes, a higher static field intensity of the MRI apparatus will shorten imaging time. In consideration of the imaging times envisioned in hospital use, this Technical Report compares measurement data for imaging performed in six directions with an apparatus having a 1,5 T static field intensity, and in six directions and 15 directions with a
