387

Tractography: Possible Applications in

Musculoskeletal Radiology
Anne Cotten, MD, PhD1,2 Farah Haddad1 Georges Hayek, MD1 Guillaume Lefebvre, MD1
Emilie Dodré, MD1 Jean-François Budzik, MD, PhD1,2,3

1 Service de Radiologie et Imagerie Musculosquelettique, Centre de
Consultations et d’Imagerie de l’Appareil Locomoteur (CCIAL), CHRU
de Lille, rue du Pr Emile Laine, Lille Cedex, France
2 EA4490-PMOI, Université du Littoral-Côte d’Opale, Laboratoire de
Physiopathologie des Maladies Osseuses Inflammatoires, Boulogne
sur Mer Cedex, France
3 Imagerie Médicale, GHICL, Hôpital St-Vincent-de-Paul, Lomme,
France
Address for correspondence Anne Cotten, MD, PhD, Service de
Radiologie et Imagerie Musculosquelettique, Centre de Consultations
et d’Imagerie de l’Appareil Locomoteur (CCIAL), CHRU de Lille, rue du
Pr Emile Laine, 59037 Lille Cedex, France
(e-mail: anne.cotten@chru-lille.fr).

Downloaded by: Collections and Technical Services Department. Copyrighted material.

Semin Musculoskelet Radiol 2015;19:387–395.

Abstract Tractography (or fiber tracking) consists of three-dimensional modeling of the prefer-
ential movement of water molecules in the form of fiber tracks from the tensor field
information. This technique allows a new approach for the microarchitectural analysis of
Keywords anisotropic structures such as nerves, white matter, and muscles. Many disorders have
► diffusion tensor been studied including cervical myelopathy, carpal tunnel syndrome, nerve root
imaging compression, and nerve tumors. Muscles have been less evaluated. Tractography is
► diffusivity still a research technique, and its validation and widespread routine clinical use will
► fractional anisotropy require a good deal of work toward a harmonization of the MRI protocols and data
► tractography postprocessing methods.

Diffusion Imaging and Diffusion Tensor
Imaging
Diffusion imaging demonstrates the random diffusion of
extracellular water molecules in tissue. This is usually accom-
plished through the use of spin-echo single-shot diffusion-
weighted echo-planar imaging with a bipolar diffusion-en-
coding gradient in three directions. The apparent diffusion
coefficient (ADC) quantifies water molecules displacement
and as a consequence provides indirect information about the
structures surrounding these molecules. Such diffusion can
be isotropic, with the movement of water molecules occur-
ring freely in all directions in space, or anisotropic, with the
overall diffusion of water molecules occurring in a preferred
direction. In highly ordered tissues such as the spinal cord and
nerves, the molecular motion of water preferentially occurs
along one axis, the axis of the axons, with much less motion in
a direction perpendicular to that axis. As a consequence,
measuring anisotropy of these structures provides informa-
tion about the orientation and architectural organization of
the tissue.
Diffusion tensor imaging (DTI) allows this assessment. DTI
is a further development of the previous technique that
applies gradients in at least six directions. The purpose is to
obtain more precise information not only regarding the
overall diffusion of water inside the tissue, but also regarding
its preferred direction. The higher the number of directions
along which the diffusion gradients are applied, the more
precise the determination of anisotropy. However, a large
number of directions increases the acquisition time and
therefore the motion blur.1 In fact, the choice of this number
depends on the structure to assess because six directions can
be enough for a median nerve, which has a vertical direction,
but 15 to 25 directions can be required for a brachial plexus.
The b factor expresses the power of the diffusion gradients
in seconds per millimeter squared. When b increases, the
power of the gradients increases, the diffusion weighting of
the sequence increases, but the signal-to-noise ratio, which is

Issue Theme Update on Advances in Copyright © 2015 by Thieme Medical DOI http://dx.doi.org/
Musculoskeletal Magnetic Resonance Publishers, Inc., 333 Seventh Avenue, 10.1055/s-0035-1563736.
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388 Tractography Cotten et al.
critical in fiber tracking, decreases. So this choice is impor-
tant. In general, the b values used for musculoskeletal imaging
are frequently
700 to 1,000 s/mm2. A compromise thus has
to be found between a good signal-to-noise ratio, good spatial
resolution, and an acceptable acquisition time. The balance
between the diffusion-specific parameters and those com-
mon to all MRI sequences is essential for the achievement of
DTI images that allow efficient and reliable postprocessing of
data.
The diffusion gradients applied in at least six directions
provide information on the diffusion inside each voxel exam-
ined. This can be schematized by a three-dimensional (3D)
ellipsoid formed because of three main vectors, each having
its own magnitude, in the dominant direction and in the two
perpendicular directions. In simpler terms, the preferred
diffusion directions can be depicted by mappings using a
specific color code initially used in neuroradiology such as
blue for the craniocaudal direction, red for the left-to-right
direction, and green for the anteroposterior direction. These
maps can be superimposed with corresponding anatomical
images.
DTI parameters can be calculated voxel by voxel using
software applications such as MedINRIA. These are the two
main parameters:
-Overall diffusivity, which can be expressed either by
means of ADC or in terms of average diffusivity. The
more obstacles the molecules encounter, the less they
move and the weaker the diffusion. This diffusivity corre-
sponds to the following mathematical formula: λ ¼ (λ1þ
λ2þ λ3)/3.3–5 Diffusivity can be divided into axial diffusiv-
ity, designated by λ1 (the magnitude of the dominant
direction), and radial diffusivity designated by (λ2þ λ3)/
2, the average magnitude of the two other directions.
Differentiating between these two types of diffusion can
be useful, especially when evaluating nerves and white
matter.6
-Fractional anisotropy (FA), which quantifies the direction-
al dependence of water diffusion. The values range from 0
to 1. The higher the FA, the more the water molecules will
be “forced” to diffuse in a preferential direction. A high FA
usually indicates good integrity of the structure.
To obtain these parameters, cross-sectional area measure-
ments can be calculated on the FA maps.
Tractography
Tractography (or fiber tracking) is a powerful extension of the
previous technique. It consists of 3D modeling of the prefer-
ential movement of water molecules in the form of fiber
tracks from the tensor field information. The fibers’ tracking
and display criteria vary according to the software used. In
our department, we use MedINRIA, which allows tractogra-
phy of the entire volume obtained with MRI. The aim of the
software is to interconnect voxels having similar main vectors
and FA values, on the assumption that voxels whose proper-
ties are comparable belong to the same tissue (line propaga-
tion method).1 Several parameters may be taken into account
Seminars in Musculoskeletal Radiology Vol. 19 No. 4/2015
for fiber tracking. The main ones are the FA threshold value,
the b0 threshold value (allowing the elimination of noise), the
angulation threshold of the fiber, and its minimal length. As a
rule, the software uses a combination of several of these
parameters to display the fibers. Once the tractography
algorithm has been launched on the FA mapping, it is thus
possible to obtain a 3D modeling of the structure under study.
The color coding is the same as that used in FA maps, and
anatomical fusion with T1- or T2-weighted sequences allows
us to estimate the relevance of the reconstructions. The
volume under study can then be manually restricted to the
structure of interest. The structure is then analyzed with
FiberViewer software, which can provide the DTI measure-
ments along the structure on a curve.
Measuring these DTI parameters with a FiberViewer on
tractography images rather than using region of interest (ROI)
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on FA maps probably does not change much for large and
vertical structures such as the median nerve, but for the
assessment of thin or complex structures such as the lumbar
nerves or the brachial plexus, this can be particularly useful.
For example, in the presence of a compressed lumbar nerve by
a disk herniation, you need to avoid partial volume effects, but
you need sufficient information, which of course will be a
problem at the level of the nerve root compression. Tractog-
raphy allows the nerve to be followed at the level of the
compression and the microstructural parameters to be mea-
sured along the course of the nerve. This explains why
measurements of DTI parameters may be more reliable on
tractography than by using ROI, at least for some structures.7
Spinal Cord
The white matter of the spinal cord is made up of well-
arranged clusters of nerve fibers, vertically oriented, whose
anisotropy is therefore marked (far more so than that of the
gray matter).8 MRI is the imaging modality of choice for the
assessment of cervical spondylotic myelopathy. However,
abnormal signal intensity of the spinal cord, especially on
T2-weighted images, is poorly correlated with the clinical
symptoms, because it may be noticed in various lesions
whose severity varies greatly.9,10 Tensor diffusion imag-
ing11–14 and tractography15 have enabled the evidence of a
change in the microarchitectural parameters of the spinal
cord, even when no abnormal spinal cord signal is detected on
conventional sequences. The drop in FA, which appears to be
more sensitive than the increase in mean diffusivity
(MD),15,16 appears to be correlated in tractography with
the severity of the clinical impairment,15,17,18 even though
not all teams have observed this14 (►Fig. 1). We may suppose
that in case of edema, the spinal cord retains its fibrillar
architecture (the drop in FA is not marked), in contrast with
medullary necrosis and cavitation, accompanied by an FA
drop because water can diffuse much more freely. And this is
particularly important, as the predictive value of DTI regard-
ing postoperative outcome has been reported.19 The alter-
ations of the visual aspect of the tractography (normal,
indentation, partial or complete interruption) and the num-
ber or length of the fibers counted by the software have been
 Tractography Cotten et al. 389

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Fig. 1 Cervical spondylotic myelopathy in a 59-year-old woman with severe functional impairment. (a) Sagittal T2-weighted image shows
increased signal intensity of the spinal cord. (b) Interruption of fibers (suggesting the tissue became isotropic) and spinal narrowing on the
diffusion tensor imaging-fiber tractography image. (c) Blown-up image of the tractography in the area of compression with an important
fractional anisotropy (FA) drop at the compressed site on the FA histogram. (d) The segmented spinal cord. Fig. 1a–c reprinted with permission
from reference 15.

Fig. 2 Tractography of the median nerve inside the distal carpal

tunnel in a volunteer.

diversely correlated with the severity of the clinical damage

and with the patient’s prognosis; to date, the results are still
unconvincing.16,20,21
Tractography-based DTI measurements can also quantify
the degeneration of specific tracts of white matter.22 This
specific assessment might allow depiction of more subtle
Fig. 3 Postsurgical neuroma affecting the three-dimensional visuali-
zation of the median nerve fibers. The mass effect of the disk
herniation is clearly demonstrated.

Seminars in Musculoskeletal Radiology Vol. 19 No. 4/2015

390 Tractography Cotten et al.

changes or unilateral abnormalities that can not be detected
by the assessment of the whole cord.
Tensor diffusion imaging and tractography have also been
used to evaluate other disorders of the spinal cord (traumatic
lesions, tumors, arteriovenous malformations, myelitis, com-
pression, diastematomyelia, and attached long spinal cord),
but most of them are evaluated by neuroradiologists.
Peripheral Nerves
The peripheral nerves also represent strong anisotropic struc-
tures. The median nerve is the most studied peripheral nerve
in the literature due to its large caliber, its rectilinear course
(►Fig. 2), the frequency of disorders affecting it at the wrist,
and the ease of its electroneurologic and MRI evaluation.
Carpal Tunnel Syndrome
In patients presenting a carpal tunnel syndrome, most au-
thors have reported a decrease in FA.2,23–27 However, FA
varies along the carpal tunnel; it tends to increase distally
in controls (as the fibers go through a smaller space) and to
decrease in patients (intrafascicular edema).23,28,30 An anal-
ysis of the difference between the distal and proximal meas-
urements could thus increase the sensitivity of the results.
However, an unchanged value23–25,27 or an increase in
ADC2,24,29 has also been reported in the literature.

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Fig. 4 Tractography of the right S1 root with anatomical correspondence in a patient with a right posterolateral disk herniation. The mass effect is
clearly seen on the (a) lateral and (b) frontal views. The fractional anisotropy can be measured along the compressed nerve root, the blue mark
showing the part of the nerve being measured (c). Fig. 4a, b reprinted with permission from reference 7.

Seminars in Musculoskeletal Radiology Vol. 19 No. 4/2015


The apparent heterogeneity of these results may be ex-
plained by the diversity of the protocols used, but also by the
varying severity of the carpal tunnel syndrome. Indeed, even
if a good correlation has been reported between the changes
in the DTI parameters and the electroneurography
data,24,29–31 this type of measurement seems to lack sensi-
tivity to detect moderate nerve compressions.23,29 Moreover,
a great variability of the diffusion parameters has been
reported in normal subjects,28,32,33 which explains why it
is difficult to define a threshold value enabling a distinction
between health and disease. Finally, these parameters must
be analyzed according to the age of the patient. Indeed,
changes in diffusion and anisotropy similar to those observed
in carpal tunnel syndrome may develop with age, in the
absence of any clinical symptoms.2,28,29 Conversely, the sex
of the patient does not seem to influence the values of the
diffusion parameters.
A single study has focused on the recurrence of carpal
tunnel syndrome after surgery.30 Patients showed a decrease
in diffusion, but the FA, which quantifies the structural
integrity of the nerves, was intact. In addition, those with
endoneurial fibrosis (defined by an enlarged median nerve
and endoneurial enhancement after gadolinium injection)
had lower ADC and radial diffusion values than those without
fibrosis. Endoneurial fibrosis may thus impede the free
diffusion of water but also affect the myelin rather than the
axon because axial diffusion, which informs about axon
integrity, was less affected (intrafascicular scar).34,35 The
usefulness of the 3D visualization of the median nerve by
this technique has not yet been fully assessed (►Fig. 3).
Other Nerves
Ulnar Nerve
The ulnar nerve at the cubital tunnel has been evaluated less
often. Interestingly, discontinuity of the nerve proximal to the
medial epicondyle, indicating a more proximal compression
than in the cubital tunnel, has been reported.36
Fig. 5 Tractography of the roots of the brachial plexus.
Tractography Cotten et al. 391
Spinal Nerves
A decrease in FA and an increased diffusivity in cervical or
lumbar nerve roots compressed by a disk herniation have
been reported in the literature (►Fig. 4).37–39 Similar changes
in DTI parameters were also reported in patients with nerve
root pain in the absence of compression.38 These parameters
could thus be correlated with the clinical data, regardless of
the existence of a nerve root compression.38 In a recent
study,37 the clinical data were correlated with MD and axial
and radial diffusivity values, but not with FA values, suggest-
ing that demyelination, axonal swelling, and edema or in-
flammation of the adjacent tissues are more responsible for
the symptoms observed in the case of nerve compression
than the alteration of axonal density. Tractography can also
perfectly demonstrate a mass effect, a narrowing or complete
interruption of the tracted root, but its contribution as
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compared with classical morphological sequences remains
to be specified. This imaging method could, however, perhaps
prove useful to reveal evidence of extraforaminal nerve
compression.40 The achievement of a good quality tractog-
raphy of lumbar roots at 3 T is fostered by the use of reduced
fields of view to avoid some artifacts such as distortion of the
dural sac, which are more pronounced at this magnetic
field.41
Brachial and Sacral Plexus
DTI-derived measurements and fiber tractography of brachial
plexus has been described in volunteers,42 but its usefulness
in pathology has not been studied extensively (►Fig. 5). The
sacral plexus may also be tracked up to the root of S3 and to
the pudendal nerve, with possible involvement in the evalu-
ation of spina bifida with neurogenic bladder.43 A truncated,
irregular, and disorganized appearance of roots S1 to S3 with
a decrease in FA has also been reported in women with
painful pelvic endometriosis,44 suggesting associated proxi-
mal microstructural nerve injury, and may perhaps partially
explain the possibility of persistence or recurrence of pain
after surgical removal of the pelvic endometriosis lesions.
Seminars in Musculoskeletal Radiology Vol. 19 No. 4/2015
392 Tractography Cotten et al.

Particular Indications

Axonal Degeneration and Regeneration

The studies published in the literature have mainly focused on
animal models. In case of injury to the sciatic nerve by
compression or stretching, FA decreases during the phase
of Wallerian degeneration and increases during the regener-
ative phase.45–47 Tractography may represent an attractive
means of visualizing nerve interruption and its regeneration
over time.46,48

Tumors and Pseudotumors

The 3D depiction of nerves in tractography could also
be used to study the relationship between a lesion and
a nerve structure, particularly when planning surgery
(►Figs. 6 and 7). Some authors have reported a higher

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frequency of interruption or complete disorganization of
the fibers in case of malignant tumors, whereas benign
tumors are more often associated with a normal appearance,
a deviation, or a partial interruption of the fibers.49–53
However, it is important to recall that we are dealing with
functional imaging and not with direct anatomical imaging.
Therefore, areas of axonal degeneration and/or associated
loss of myelin may result in a focal loss of fibers, whereas the
fasciculate anatomical architecture may still be preserved.

Muscle
Muscle has been less studied in DTI and tractography
Fig. 6 Tractography of a cystic schwannoma of the ulnar nerve. Note
the eccentric location of the tumor. (►Fig. 8). Certain histologic features explain the necessary

Fig. 7 (a) T2-weighted image and (b) tractography of the relationship between the proximal aspect of a schwannoma and the tibial nerve (patient with
neurofibromatosis type 2). Note the eccentric location of the tumor.

Seminars in Musculoskeletal Radiology Vol. 19 No. 4/2015


Fig. 8 Anterior view of a vastus intermedius tractography in a
volunteer.
adaptation of the sequences.4,54 Compared with white mat-
ter, the T2 of the muscle is weaker, thus causing a decrease in
the signal-to-noise ratio in diffusion imaging.4 The FA value is
low in muscles, and the average diffusion is higher. Conse-
quently, fiber tracking will require a low FA threshold, which
will increase the risk of noise-induced parasite fibers.55
Moreover, diffusion will take place in a less precise direction.
Finally, the muscle cells are surrounded by fat, which is liable
to cause a partial volume effect between the water signal and
the fat signal.
Most publications deal with the feasibility of the technique
for the study of muscle architecture4,56–59 and with the
evidence of changes in the fibers, particularly in their pen-
nation angle.3,52 Age does not appear to influence these
parameters.52,60,61 Potential usefulness in muscle trau-
ma,62,63 muscular dystrophies,64 and the effects of denerva-
tion,65–67 ischemia, and reperfusion68 has been reported but
remains to be extensively studied.
Tractography Cotten et al. 393
Conclusion
Tractography can provide beautiful 3D images and enable
precise objective measures in terms of microstructural
changes of nerves, white matter, and muscles. But this is still
a research technique, and its validation and widespread use in
clinical routine will continue to require a good deal of work
for the harmonization of MRI protocols and data postprocess-
ing methods.
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Seminars in Musculoskeletal Radiology Vol. 19 No. 4/2015