ISO/TR 16379:2014
(Main)Tissue-engineered medical products — Evaluation of anisotropic structure of articular cartilage using DT (Diffusion Tensor)-MR Imaging
Tissue-engineered medical products — Evaluation of anisotropic structure of articular cartilage using DT (Diffusion Tensor)-MR Imaging
ISO/TR 16379:2014 has been prepared for evaluation of therapeutic courses for articular cartilage disease and summarizes results from structural evaluation of knee joint cartilage by diffusion tensor imaging, an MRI applied technology allowing non-invasive observation of soft tissue morphology in vivo. ISO/TR 16379:2014 is intended for use in areas such as regenerative medicine for knee joint cartilage disease.
Produits médicaux à base de tissus — Évaluation de la structure anisotrope du cartilage articulaire en utilisant l'imagerie en tenseur de diffusion (IRM-TD)
General Information
Standards Content (Sample)
TECHNICAL ISO/TR
REPORT 16379
First edition
2014-03-01
Tissue-engineered medical
products — Evaluation of anisotropic
structure of articular cartilage using
DT (Diffusion Tensor)-MR Imaging
Produits médicaux à base de tissus — Évaluation de la structure
anisotrope du cartilage articulaire en utilisant l’imagerie en tenseur
de diffusion (IRM-TD)
Reference number
ISO/TR 16379:2014(E)
©
ISO 2014
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ISO/TR 16379:2014(E)
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ISO/TR 16379:2014(E)
Contents Page
Foreword .iv
Introduction .v
1 Scope . 1
2 Terms and definitions . 1
3 Principle . 3
4 Diffusion tensor magnetic resonance imaging (DT-MRI) data observation in
articular cartilage . 3
4.1 DT-MRI measurement process . 3
4.2 Notes on setting of DT-MRI imaging parameters for articular cartilage . 4
4.3 Measurement indices for structural evaluation of articular cartilage by DT-MRI . 5
Annex A (informative) Measurement Results .10
Bibliography .23
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ISO/TR 16379:2014(E)
Foreword
ISO (the International Organization for Standardization) is a worldwide federation of national standards
bodies (ISO member bodies). The work of preparing International Standards is normally carried out
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The committee responsible for this document is ISO/TC 150, Implants for Surgery, Subcommittee SC 7,
Tissue-engineered Medical Products.
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ISO/TR 16379:2014(E)
Introduction
Structural evaluation of articular cartilage with conventional diagnostic technologies is challenging,
and Nihon University has developed technologies (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 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 Medicine”, 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.
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TECHNICAL REPORT ISO/TR 16379:2014(E)
Tissue-engineered medical products — Evaluation of
anisotropic structure of articular cartilage using DT
(Diffusion Tensor)-MR Imaging
1 Scope
This Technical Report has been prepared for evaluation of therapeutic courses for articular cartilage
disease and summarizes results from 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 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
characteristics. 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 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 ask 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 restricted 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 cartilage anisotropy data for use as standardized data in
longitudinal diagnosis following transplant of articular cartilage as a regenerative treatment.
2 Terms and definitions
For the purposes of this document, the following terms and definitions apply.
2.1
diffusion tensor
DT
tensor expressing the orientation and magnitude of diffused proton signals
2.2
sequence
protocol for performance of MRI
2.3
spin-echo echo-planar imaging
SE-EPI
method 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 sequence
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ISO/TR 16379:2014(E)
2.4
field of view
FOV
width and height of an imaged region (expressed in cm or mm)
2.5
matrix
pixel resolution for acquisition of MR signals in a field of view
2.6
echo time
TE
time after RF pulse application until an echo is produced
[SOURCE: JIS K 3611]
2.7
radio frequency pulse
RF pulse
short duration, high-frequency electromagnetic wave in pulse form
[SOURCE: JIS K 3611]
2.8
repetition time
TR
time interval for repetition of the basic unit of magnetic resonance pulse sequences
[SOURCE: JIS K 3611]
2.9
slice thickness
thickness of the imaging plane
2.10
number of averages
NA
number of times an identical MR signal is repeated
2.11
b value
maximum value of the parameter indicating level of diffusion weighting
2.12
motion probing gradient
MPG
gradient field applied to detect diffusion
2.13
parallel imaging
high-speed imaging method making use of the difference in sensitivities provided by multiple coils
2.14
fractional anisotropy
FA
number indicating level of structural anisotropy
2.15
mean diffusivity
MD
mean of diffusion coefficients along the three primary axes of a diffusion tensor
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ISO/TR 16379:2014(E)
2.16
signal-to-noise ratio
SNR
value expressing the proportion of signal to noise; greater values indicate higher image quality
2.17
voxel
three-dimensional cuboid representing the minimum unit comprising a three-dimensional image
3 Principle
In the regeneration medicine for artificial cartilage, 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 cartilage 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 vertically 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 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 evaluated 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 cartilage
4.1 DT-MRI measurement process
The 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, and 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.
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ISO/TR 16379:2014(E)
Figure 1 — DT-MRI data measurement process
Table 1 — MRI apparatus, signal-receiving coils, and imaging parameters used in DT-MRI
Kyoto University Nihon University School
Hiroshima University
Imaging facility Institute for Frontier of Dentistry at Matsudo
Hospital
Medical Sciences Hospital
Apparatus SONATA 1,5T Achieva 1,5T Signa Excite 3T
(Manufacturer) (Siemens) (Philips) (General Electric)
Signal-receiving coil 4 ch flex array 8 ch sense knee Lower extremity
Sequence SE-EPI SE-EPI SE-EPI
FOV [mm] 192 × 192 150 × 150 128 × 128
Matrix 192 × 192 144 × 142 128 × 128
TR [ms] 2 200 2 200 2 200
TE [ms] 70 68 68
Slice thickness [mm] 3 5 5
Number of averages 24 20 12
b-value 600 600 400
No. MPG axes 6 6 6,15
a b
Parallel imaging GRAPPA SENSE n/a
Image slice Sagittal plane Sagittal plane Sagittal plane
Pixels 384 × 384 400 × 400 256 × 256
a
Generalized rapid acquisition with partially parallel acquisition.
b
Sensitivity encoding.
4.2 Notes on setting of DT-MRI imaging parameters for articular cartilage
4.2.1 Imaging resolution
The 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 resolution but decreased SNR of MR signals, which decreases
data reliability.
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ISO/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 parameters used for this Technical Report were selected
to allow acquisition of three-layer data.
4.2.2 Repetition time
Longer 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 averages
A greater number 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-value
Higher b-values lengthen TE, which might lead to under-representation of diffusivity. Conversely, lower
b-values can 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 diffusion 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 an apparatus having a 3 T static field intensity.
4.2.6 Parallel imaging
Imaging time can be shortened by application of parallel imaging. Signal-receiving coil is required for
application of parallel imaging.
4.3 Measurement indices for structural evaluation of articular cartilage by DT-MRI
4.3.1 DT-MRI imaging slices and data measurement sites
A measurement slice is selected for acquisition of DT-MRI imaging data on articular cartilage. In a
coronal slice of the knee joint as shown in Figure 2, DT-MRI imaging is performed in the sagittal plane
at the location most inferior to the lateral condyle of the femur, and the image data acquired are used
to an create anisotropy distribution image and a mean diffusivity distribution graph, and fractional
anisotropy and mean diffusivity are measured. The measured data are graphed, with the horizontal
axis representing depth from the cartilage surface.
But as shown in Figure 3, depth from the cartilage surface is a relative measure relating the pixel centre
where data are measured to the thickness of the cartilage concerned. [See the following Formula (1)]
D
ND=×100% (1)
T
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ISO/TR 16379:2014(E)
where
ND is the depth from surface (%);
D is the distance to pixel centre of data measurement (mm);
T is the cartilage thickness (mm).
Figure 2 — DT-MRI imaging slice and data measurement site
Figure 3 — Pixel intensity measurement site and depth from cartilage surface
NOTE Enlargement of measurement site at right in Figure 2.
4.3.2 Measurement of fractional anisotropy
4.3.2.1 Purpose of measurement
Fractional anisotropy is measured to evaluate the strength of structural anisotropy corresponding to
collagen fibre orientation in articular car
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