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Diffusion Tensor Imaging of Peripheral Nerves Ali M. Naraghi, FRCR1 Haitham Awdeh, MD2 Avneesh Chhabra, MD2

Vibhor Wadhwa, MD2

1 Division of Musculoskeletal Radiology, Joint Department of Medical

Imaging, Toronto Western Hospital, Toronto, Ontario, Canada 2 Division of Musculoskeletal Radiology, UTSW Medical Center, Dallas, Texas 3 Division of MR, University of Zurich, Zurich, Switzerland

Gustav Andreisek, MD3

Address for correspondence Ali M. Naraghi, FRCR, Division of Musculoskeletal Radiology, Joint Department of Medical Imaging, University of Toronto, Toronto Western Hospital, 399 Bathurst Street, Toronto, Ontario, Canada, M5T 2S8.

Abstract

Keywords

► diffusion tensor imaging ► MRI ► peripheral nerves ► MRN

Diffusion tensor imaging (DTI) is a powerful MR imaging technique that can be used to probe the microstructural environment of highly anisotropic tissues such as peripheral nerves. DTI has been used predominantly in the central nervous system, and its application in the peripheral nervous system does pose some challenges related to imaging artifacts, the small caliber of peripheral nerves, and low water proton density. However advances in MRI hardware and software have made it possible to use the technique in the peripheral nervous system and to obtain functional data relating to the effect of pathologic processes on peripheral nerves. This article reviews the imaging principles behind DTI and examines the literature regarding its application in assessing peripheral nerves.

With advances in T2-based magnetic resonance neurography (MRN), high-resolution imaging of peripheral nerves is achievable, depicting morphological changes such as alterations in nerve caliber, fascicular pattern, and signal intensity in a variety of peripheral neuropathies of different etiologies. Diffusion tensor imaging (DTI) is an MR imaging technique providing functional information that in many ways can be viewed as a complementary technique to MRN in the assessment of peripheral nerve lesions. DTI and fiber tractography have been studied extensively in the evaluation of central nervous system (CNS) disorders including CNS tumors, psychiatric and cognitive disorders, neurodegenerative and demyelinating conditions, epilepsy, and multiple sclerosis.1 By comparison, DTI evaluation of the peripheral nervous system is still in its infancy, having been studied most extensively in the assessment of the median nerve at the wrist and peripheral nerve sheath tumors. This article reviews the technical aspects of DTI and fiber tracking, with an emphasis on peripheral nerves, and reviews the literature relating to the applications of DTI in the peripheral nervous system.

Issue Theme Advanced Imaging of Peripheral Nerves; Guest Editor, Avneesh Chhabra, MD

Background Water molecules and mobile protons undergo diffusion, or Brownian motion, whereby there is random displacement of molecules as a result of their inherent thermal energy. The magnitude of this displacement depends on the diffusion coefficient, with a higher diffusion coefficient reflecting a greater degree of displacement. In clinical practice, however, the displacement encountered not only depends on passive diffusion but also on active transport mechanisms. Furthermore, biological structures, such as cell membranes, can also alter the magnitude of displacement of mobile protons. The principle of diffusion forms the basis of diffusion-weighted (DW) MR imaging and has been extensively studied across a range of organ systems to detect and distinguish between different pathologic entities. Although such microscopic motion is imperceptible on routine pulse sequences, MRI can be used to detect diffusion by adding a pair of diffusion-sensitizing gradients before and after a 180-degree refocusing pulse.2 The diffusion-sensitizing gradients are of the same orientation and magnitude. As a

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DOI http://dx.doi.org/ 10.1055/s-0035-1546824. ISSN 1089-7860.

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Semin Musculoskelet Radiol 2015;19:191–200.

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result, spins that have not undergone any spatial displacement between the two diffusion-sensitizing gradients will undergo rephrasing and demonstrate no overall signal loss, as opposed to spins that have undergone spatial displacement between the application of the diffusion-sensitizing gradients that will undergo incomplete rephrasing and demonstrate net signal loss. The degree of signal loss depends on the apparent diffusion coefficient (ADC) and the b-value of the pulse sequence acquisition. Tissues with higher ADC values have a greater net loss in signal intensity on DW imaging due to the greater diffusion. The b-value is dictated by the duration and amplitude of the diffusion-sensitizing gradients and has the units of seconds/mm2.2 DW imaging is typically performed with one data set with a b-value of 0 and at least one other data set with a higher b-value. Higher b-values are thought to maximize sensitivity for detecting changes in ADC.3 As an extension of DW, diffusion tensor imaging (DTI) evaluates the direction as well as the magnitude of diffusion. This is especially relevant in biological tissues displaying ordered and longitudinally oriented fibers, such as white matter tracts in the CNS, peripheral nerves, and skeletal muscles. In isotropic tissues, diffusion is equal in all directions because there are no barriers to diffusion, but in anisotropic tissues, such as neural tissue, diffusion is greater in one direction. These differences in the properties of tissues form the basis of DTI. DTI is achieved by applying diffusion-sensitizing gradients in multiple directions, allowing diffusion to be displayed as a matrix model reflecting the three-dimensional (3D) characteristics of diffusion and anisotropy along x, y, and z axes. The diffusion-sensitizing gradients must be applied in at least six non-colinear directions, although in practice the number of directions exceeds this. In isotropic tissues the 3D pattern of diffusion will result in a sphere because diffusion is of equal magnitude in all directions (►Fig. 1a). However, in anisotropic tissues, diffusion will be predominantly in one direction with reduced diffusion in other directions. The predominant direction of diffusion is referred to as the principal eigenvector, and diffusion along axes perpendicular to the principal eigenvector are referred to as secondary and tertiary eigenvectors. This will result in an ellipsoid configuration (►Fig. 1b). The principal or first eigenvalue is also referred to as axial or parallel diffusivity, whereas second and third eigenvalues perpendicular to the nerve are also referred to as radial or perpendicular diffusivity.

Technical Aspects of DTI of Peripheral Nerves Optimal DTI of peripheral nerves requires imaging with high signal-to-noise ratio (SNR), short acquisition time, high spatial resolution, and a lack of artifacts. However, as discussed later, improvements in some areas often result in trade-offs in other areas. In practice, DTI is typically performed by utilizing singleshot echo-planar imaging (EPI).4 The main benefits of utilizing EPI are the high SNR and the acquisition time. SNR is an important consideration in DTI because low SNR affects the accuracy of fractional anisotropy (FA) and diffusivity measurements. Acquisition time is also an important consideration Seminars in Musculoskeletal Radiology

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Fig. 1 Diffusion “ellipsoids” in an (a) isotropic and (b) anisotropic environment. In (a) the magnitude of diffusion is equal in all directions resulting in a sphere, whereas in (b) diffusion is greatest in the direction of the primary eigenvector λ 1 resulting in an ellipsoid.

because a shorter acquisition time can lead to fewer motion artifacts. Motion artifacts can be problematic in DTI because any macroscopic motion is significantly greater than the microscopic motion that is being probed by DTI and can result in an overestimation of ADC values. The drawbacks of EPI include multiple artifacts, such as chemical shift and ghost artifacts, and T2-related blurring.5 EPI sequences are also highly susceptible to magnetic field inhomogeneities. Strategies to minimize such artifacts include the use of spectral fat suppression, shorter echo-train lengths, tighter echo spacing, higher bandwidth, shimming, and motion correction techniques. The spatial resolution of EPI pulse sequences used in DTI are also typically lower than anatomical pulse sequences, which can lead to partial volume effects. DTI imaging can be performed at 1.5 T or 3 T. The improved SNR at 3 T is advantageous, especially when higher b-values are used. Similarly, utilizing dedicated multichannel phased array coils allows for acquisition of higher SNR images. The higher SNR afforded by 3 T and multichannel coils can be partly traded for improved spatial resolution. However, the use of 3 T may magnify the effects of any magnetic field inhomogeneities. An important requirement is an MR imaging system with high strength gradients and a high slew rate. The use of parallel imaging techniques can also be efficacious in reducing imaging time, but higher acceleration factors will result in a reduction in SNR and can cause foldover artifacts. An acceleration factor of 2 is typically used. A range of b-values have been utilized in DTI of peripheral nerves ranging from 400 to > 1,000 seconds/mm2.6–9 Andreisek et al assessed multiple b-values at 1.5 T in imaging of the median nerve and determined that the optimal b-value was 1,025 seconds/mm2 in their imaging protocol.10 Guggenberger et al identified a b-value of 1,200 seconds/mm2 as optimal in imaging of the median nerve at 3 T.11 Increasing b-values has a deleterious effect on SNR (►Fig. 2).10 Although at least six non-colinear directions are required in DTI imaging in addition to one data set with a b-value of 0 seconds/mm2, the number of diffusion encoding directions used in DTI of peripheral nerves has varied greatly. The accuracy of FA and diffusivity measurements increases with the number

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Fig. 2 Graph depicting the change in signal to noise (SNR) with increasing b-values. Images from diffusion tensor imaging of the calf show a reduction in SNR with an increase in b-values. (Image courtesy of Dr. Lawrence White, University of Toronto).

of directions, but no studies have evaluated the optimal number of directions in the peripheral nervous system. In CNS studies, it has been suggested that at least 20 directions are needed for the precise measurement of anisotropy, and 30 measurements are required to measure diffusivity.12 Increasing the number of directions will increase imaging time. Chhabra et al, in a study of peripheral nerve–related tumors, found no significant difference in ADC values using imaging protocols with 12 and 20 directions.13 A variety of specialized DTI software can be used to measure parameters related to anisotropy of the tissue under investigation. Both stand-alone software and software specific to MR vendors are available. The details of the various software programs are beyond the scope of this article, but Guggenberger et al demonstrated moderate to substantial agreement between two software packages in measuring DTI indexes of the median nerve.14 Measurements at specific points along the nerve can be made by placing a region of interest (ROI) over the structure being investigated. The software generates a variety of measures related to anisotropy of the tissue. Although specific eigenvalues can be calculated, the degree of anisotropy is more commonly expressed in terms of fractional anisotropy, ADC, and mean diffusivity. Information regarding the number and length of nerve fibers can also be obtained. FA is an overall measure of the tissue’s anisotropy and is given a value of 0 to 1, with 0 reflecting a completely isotropic environment and an FA of 1 reflecting a completely anisotropic environment. This information can also be presented visually as color-coded FA maps. The color coding depicts the direction of the principal eigenvector, with blue reflecting craniocaudal direction, green representing anteroposterior direction, and red representing mediolateral direction. The ADC value does not take the direction of diffusion into account, and mean diffusivity is a mean measure of the diffusion in all directions. Intraobserver reliability of measurement of DTI indexes in peripheral nerves is substantial to almost perfect, whereas interobserver reliability has ranged from moderate to almost perfect.14–17 The histopathologic processes involving peripheral nerves that preferentially affect FA, ADC, or diffusivity values is not well established. It has been shown, however, that pathologic processes affecting nerves, particularly after prolonged compression, include one or a combination of these

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mechanisms, that is, a breakdown of the blood–nerve barrier and vascular congestion, intraneural edema, demyelination, and Wallerian degeneration. It has been suggested that FA and axial diffusivity values reflect axonal damage rather than demyelination and, as such, may be seen in conditions causing a change in axonal density,18–22 whereas an increase in radial diffusivity is more suggestive of myelin degradation.23 Specific FA, ADC, and diffusivity values cannot be translated across platforms with different imaging acquisition parameters because they depend on many variables including magnetic field strength, SNR, number of directions of diffusion-sensitizing gradients, voxel size, age, and the nerve being studied.24,25 DTI data sets can also be used to generate tractography images. Such images are a 3D representation of anisotropic structures, and although the specifics of the DTI software and the algorithms they use differ, they essentially connect adjacent voxels with a similar direction of the principal eigenvector and anisotropy values. The quality of the tractography images partly depend on the quality of the acquired data sets and partly on the thresholds that are applied for variables such as FA values and the turning angle of the eigenvectors between adjacent voxels (►Fig. 3). The thresholds are set using the postprocessing software and help to maintain optimal tracking of the anisotropic structure from voxel to the adjacent voxels. Thresholds that are set either too low or too high can result in either the adjacent structure being erroneously included in the tractography image or parts of the structure of interest being mistaken for an adjacent structure. The tractography images can also be used to measure DTI indexes, such as FA, ADC, and diffusivity. This approach is advantageous when there is poor contrast between the nerve and adjacent structures on FA maps and can help reduce partial volume effects from inclusion of adjacent structures.

Applications of DTI in Imaging of Peripheral Nerves DTI has been utilized in imaging acute nerve injuries, compression neuropathies, inflammatory neuropathies, and peripheral nerve tumors. One of the first reports of the use of DTI in the peripheral nervous system was by Skorpil et al, who demonstrated the technique’s feasibility in evaluating the sciatic nerve of three healthy volunteers.26 Subsequently, Hiltunen et al demonstrated the feasibility of performing DTI of the peripheral nerves at the wrist, knee, and ankle.27 Since then, the main focus of DTI in assessing the peripheral nervous system has been in evaluation of the median nerve at the wrist, with limited reports regarding the performance of DTI at other peripheral sites.

Nerve Entrapment Syndromes Carpal Tunnel Syndrome Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy affecting up to 3% of the population. Clinical evaluation, aided in some cases by electrodiagnostic studies, is highly accurate in diagnosing CTS. Despite the high Seminars in Musculoskeletal Radiology

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Fig. 3 Fiber tractography of the ulnar nerve at the elbow: effect of noise and thresholds on fiber tracking. (a) Fiber tracts generated with a minimum functional anisotropy (FA) threshold of 0.4 shows coherent fibers. (b) Fiber tracts generated by reducing the minimum FA threshold to 0.15 show deviation of fiber tracking (arrow). (c) Fiber tractography obtained from poor signal-to-noise images shows inhomogeneous and discontinuous fibers.

accuracy of clinical assessment and nerve conduction studies, CTS has been the main focus of DTI. This is because, in comparison with other peripheral neuropathies, it is common, and validated diagnostic criteria have been established, making it well suited for assessing new diagnostic techniques. Additionally, use of a dedicated wrist coil leads to easier and more reproducible interrogation of relatively larger sized and superficially located median nerves.

Healthy Volunteers In 2007, Kabakci et al evaluated the DTI characteristics of the median nerve in 20 healthy volunteers using a 3-T platform and a b-value of 1,000 seconds/mm2 in 32 directions.6 They demonstrated FA values between 0.69 and 0.80 in the study subjects, with a mean of 0.71. The ADC values ranged from 0.74 to 1.27  10 3 mm2/second with a mean of 1.02  10 3 mm2/second. Multiple studies of healthy volunteers have evaluated changes in DTI indexes along the median nerve at the wrist. Kabakci et al found a significant decrease in FA of the median nerve at the level of the flexor retinaculum when compared with the distal forearm or the distal radioulnar joint (DRUJ).6 They showed no significant change in ADC values along the nerve. Guggenberger et al, using a b-value of 1,200 seconds/mm2 in 15 directions at 3 T, confirmed a significant decrease in FA distally, compared with the FA at the level of the DRUJ, in the median nerves of healthy volunteers.28 They also found a decrease in ADC from proximal to distal. By contrast, Barcelo et al16 and Stein Seminars in Musculoskeletal Radiology

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et al8 showed an increase in FA values along the median nerve of healthy individuals. Barcelo et al postulated that as the nerve passes through a more constricted space, the fiber density increases, producing reduced diffusion perpendicular to the nerve.16 This is supported by Stein et al, who showed a decrease in radial or perpendicular diffusivity as the nerve passes through the carpal tunnel, with no change in parallel diffusivity.8 Similar to the findings of Guggenberger et al,28 both studies demonstrated a decrease in ADC along the nerve. Yao and Gai did not demonstrate a significant change in FA values along the nerve in healthy controls.9 They used a b-value of 600 seconds/mm2 in six directions at 3 T. In normal individuals, several studies demonstrated a significant increase in ADC and a decrease in FA values with advancing age.6,28 Yao and Gai did not identify a change in FA or ADC values with age.9 Most studies have demonstrated no significant difference between FA and ADC of the median nerve in males and females.6,9,28 These studies also demonstrated a significant intersubject variability in DTI indexes of the median nerve. Andreisak et al, in a study of 15 healthy volunteers, found no significant sideto-side variability in FA and ADC values of the median nerve at the wrist using a 1.5-T system with a b-value of 1025 seconds/ mm2 in 25 directions.29 This suggests that the contralateral side can be used as a control. However, a significant proportion of patients with CTS have bilateral symptoms at the time of presentation, which may limit the utility of using the contralateral side as a control in pathologic cases.

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Patients with Carpal Tunnel Syndrome Khalil et al evaluated the median nerve in 13 healthy volunteers and 13 participants with CTS on a 1.5-T system with a b-value of 400 seconds/mm2 and 32 diffusion gradient directions.7 The study showed a significant decrease in FA values in patients with CTS and no significant change in ADC values between the control group and the participants with CTS. However, an overlap in FA values was observed between participants with CTS and volunteers. Other studies have confirmed a decrease in FA in participants with CTS, but most also showed a significant overlap between the control group and the CTS group.8,16,28,30 Although there are conflicting results regarding changes in FA along the median nerve in healthy volunteers, most studies showed a decrease in FA along the median nerve in participants with CTS.8,16,28 There is greater variability with regard to ADC values in CTS. Khalil et al7 and Barcelo et al16 showed no significant difference in ADC values in those with CTS compared with healthy volunteers. By contrast, several studies found a significant increase in ADC values in those with CTS.8,28,30 Bulut et al evaluated FA and ADC values in healthy volunteers as well as people with mild, moderate, and severe CTS.30 The researchers demonstrated significant differences in FA and ADC values not only between people with CTS and healthy volunteers, but also between people whose CTS differed in severity (based on electrophysiologic findings). By contrast, Barcelo et al did not find a significant correlation between electrophysiologic grading of CTS and DTI indexes.16 Koh et al compared the diagnostic performance of morphological changes of the median nerve, such as crosssectional area to DTI indexes in those with CTS and healthy volunteers.17 The analysis included the measurement of differences in the nerve at the level of the DRUJ and the flexor retinaculum. The researchers found no statistically significant differences in sensitivity and specificity between the two techniques in diagnosing CTS. However diagnostic performance was improved by using a combination of morphological features and DTI indexes. In a study of 15 subjects with CTS and 45 healthy volunteers, Guggenberger et al proposed a FA cutoff value of 0.47 10 3 mm2/second for diagnosis of CTS, with a sensitivity of 83% and a specificity of 67%.28 The proposed cutoff for ADC was 1.054  10 3 mm2/second with a sensitivity of 83% and a specificity of 54%. The researchers also proposed agespecific threshold values with their imaging technique. Bulut et al proposed a mean FA cutoff value of 0.532, with a sensitivity of 94.4% and a specificity of 70.8% for the diagnosis of CTS.30 The proposed cutoff value for ADC was 1.047  10 3 mm2/second with a sensitivity and a specificity of 81.9% and 77.1%, respectively. Taking a slightly different approach, Barcelo et al suggested measuring the difference in FA values between the level of the hamate and the DRUJ as a diagnostic criterion for CTS.16 The researchers suggested that a decrease in FA of at least 0.058 had the best sensitivity for the diagnosis of CTS. This is similar to the concept used in comparing the cross-sectional area of the proximal nerve with the crosssectional area of the nerve at the level of the pisiform for the morphological diagnosis of CTS.31

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Two studies involving a small number of participants with CTS evaluated changes in DTI indexes of the median nerve following carpal tunnel release. Hiltunen et al demonstrated a decrease in mean diffusivity, parallel diffusivity, and perpendicular diffusivity following carpal tunnel release but did not show significant change in FA following surgery.32 Naraghi et al demonstrated an increase in FA of the median nerve at 6 weeks and 6 months following carpal tunnel release. The differences between the two studies can be related to measurement techniques, as well as severity of CTS symptoms in the study subjects.33 Study results conflict, likely because of study design, sample size, and imaging factors, such as b-value and SNR. Another important factor in pathologic cases could be the heterogeneity of patient populations across different studies because the pathologic processes, and hence the DTI correlates, are likely to vary with severity of the disease.

Other Entrapment Neuropathies Recently, Bäumer et al demonstrated the utility of DTI in diagnosing ulnar nerve entrapment at the cubital tunnel.34 Demonstrating a decrease in FA values of the ulnar nerve in subjects with reduced nerve conduction velocities on electrodiagnostic tests, the researchers also showed a correlation between the FA value and the nerve conduction velocity. Qualitative assessment of FA maps demonstrated a sensitivity of 83% and a specificity of 80% for reduced nerve conduction velocity. Similar to changes in the median nerve at the wrist, they further demonstrated a decrease in FA with age. The study also evaluated T2 relaxometry of the ulnar nerve, and although there was a correlation between T2 relaxation times and reduced nerve conduction velocities, the correlation was not as strong as that for FA values. Assessment of other nerve entrapment neuropathies with DTI has been lacking, although Zhou et al demonstrated the feasibility of imaging the ulnar and median nerves, in addition to the superficial radial nerve throughout the forearm.35,36

Acute Nerve Injuries In a rabbit model of sciatic nerve crush injury, Yamasaki et al compared DTI at 7 T with histology.37 DTI was performed before injury and at various time points up to 8 weeks after injury. The researchers demonstrated a decrease in FA and an increase in radial diffusivity during the degenerative phase of the injury, and an increase in FA and a decrease in radial diffusivity during nerve regeneration, approaching normal values between 6 and 8 weeks postinjury. Histologically, the axons demonstrated loss of myelin, as well as Wallerian and axonal degeneration, with recovery seen between 4 and 8 weeks. The number of axons and ratio of myelinated axons postinjury correlated with changes in FA, yet there was also a correlation between FA and recovery of motor function. In a rat model of sciatic nerve crush injury, Morisaki et al demonstrated similar findings at 4.7 T with a decrease in FA and an increase in radial diffusivity during nerve degeneration followed by an increase in FA and a decrease in radial diffusivity during nerve regeneration in a group with a Seminars in Musculoskeletal Radiology

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Fig. 4 Traction injury. A 28-year-old man with recent right shoulder dislocation with weak right arm. (a) Sagittal and (b) coronal three-dimensional (3D) T2-weighted images show normal spine and intrathecal nerve roots. (c) Axial T1-weighted image shows right rotator cuff and pectoral muscle atrophy (arrows). (d) Coronal 3D inversion recovery turbo spin-echo image and (e) coronal 3D diffusion-weighted (DW) reverse fast imaging with steady-state free precession (PSIF) images show diffuse increased signal of the median, ulnar, and radial nerves (arrows). Notice selective peripheral nerve depiction on DW PSIF and maximum-intensity projection diffusion tensor images with inverted contrast (f, g) and diffuse increased signal. All nerves showed reduced functional anisotropy (0.2–0.3) and increased apparent diffusion coefficient (1.2–1.3 10–3 mm 2 / second) values. No neuroma or discontinuity was seen.

temporary injury.21 There was no recovery of FA or radial diffusivity in a group with a permanent injury. In this study, the FA and radial diffusivity values did not return to preinjury levels in the temporary group, but the duration of follow-up (4 weeks) was shorter than the study by Yamasaki et al. In vivo traction injuries to the sciatic nerve of rabbits showed similar changes with a reduction in FA.38 At the site of injury, the reduction in FA was seen within 1 day, and recovery began within 1 week, with a return to preinjury levels by 8 weeks. Recovery of FA values predated functional recovery. Radial diffusivity showed an increase within 1 day, recovery beginning at 1 week and returning to normal within Seminars in Musculoskeletal Radiology

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4 weeks. The magnitude of changes varied along the nerve, with the most severe at the traction site, followed by the distal and the proximal segments. There was no change in ADC and parallel diffusivity. Clinical imaging in patients with traction and laceration injuries to the nerves shows increased signal intensity on two-dimensional and 3D T2-weighted images as well as increased signal on DTI. Selective nerve depiction is seen on DWI and DTI images. Correspondingly, lowering of FA and increased ADC values are seen compared with contralateral or unaffected regional similar size nerves (►Fig. 4). Lehmann et al, examining crush injuries in rat sciatic nerves at 11.7 T, demonstrated no correlation between radial

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diffusivity and axon counts. However, the researchers showed a correlation between parallel diffusivity and FA and the number of regenerating axons.20 Meek et al reported DTI findings in a case following median nerve repair for nerve laceration at the wrist,39 utilizing fiber tractography to demonstrate progressive distal extension of the nerve over time.

Chen et al were able consistently to identify the C5–C8 nerve roots by tractography.40 DTI indexes were measured in the postganglion segment or distal to the site of compression to minimize cerebrospinal fluid and blood pulsation artifacts. There was no significant side-to-side or between-level differences from C5 to C8 in FA or any diffusivity measures in healthy volunteers. However, in symptomatic individuals, the FA was lower than the contralateral side and the FA in healthy volunteers. All diffusivity values on the symptomatic side were higher than the contralateral side. Several studies have demonstrated the feasibility of performing tractography of lumbar nerve roots in people with unilateral sciatica and healthy volunteers. 41–43 These studies showed a lower FA and a higher mean diffusivity and ADC in the compressed nerve roots in comparison with the contralateral side and healthy volunteers. Similar to cervical roots, there was no side-to-side difference in healthy volunteers. Tractography images can also show distortion and even disruption of the nerve root tracts at the site of compression. In general, FA values of lumbar and cervical nerve roots appear to be lower than those reported for peripheral nerves, such as the median nerve. This could be related to histologic differences in the endoneurium, perineurium, and epineurium of nerve roots in comparison with peripheral nerves or, more likely, less SNR with deeply located nerves and lack of dedicated use of neck coils.41

Fig. 5 Diffusion tensor imaging of lumbosacral (LS) plexus. Coronal tractography image of the LS plexus in a healthy volunteer shows symmetrical normal thickness tracts bilaterally in the LS plexus and femoral nerves (arrows).

Budzik et al utilized reduced field-of-view imaging to assess lumbar nerve roots.44 This technique in its various forms45–47 can be used to obtain signal from a ROI. It allows for imaging with reduced echo train and shorter TE, and has the additional benefit of diminishing blurring and chemical shift artifacts. Use of a relatively lower b-value of 600 to 800 brings back the needed SNR in the lumbosacral plexus (►Fig. 5). A potential drawback of the technique is longer acquisition time. In comparison with full field-of-view imaging of lumbar spine nerve roots, Budzik et al demonstrated reduced artifacts and improved image quality with better delineation of neural structures using reduced field-of-view DTI.44

DTI of Soft Tissue Tumor and Peripheral Nerves Chhabra et al evaluated a variety of peripheral nerve tumors using DW imaging and DTI.13 The researchers demonstrated a

Fig. 6 Residual recurrent schwannoma. Three-dimensional inversion recovery turbo spin-echo maximum-intensity projection image in an elderly woman with a past history of operated schwannoma in the right supraclavicular region, with incomplete resection due to interfascicular involvement of the lesion in the right C5 and C6 nerve roots as well as the upper trunk. She complained of increasing pain in the C5–C6 distribution for many months. There is enlargement of the right C5–C6 roots and upper trunk (arrow). Corresponding diffusion tensor imaging shows partial disruption of otherwise tracts (arrow). The apparent diffusion coefficient value of the lesion is 1.4  10–3 mm 2 /second, and the functional anisotropy of the right C5 and C6 nerves was reduced to 0.2 to 0.3. Seminars in Musculoskeletal Radiology

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significantly lower ADC in malignant lesions compared with benign lesions using DTI but not DWI. The difference between the techniques was thought to be due to the higher b-value used with DTI (1,000 seconds/mm2 versus 800 seconds/mm2). FA values were lower in lesions than the contralateral normal nerves (►Fig. 6). By comparison, Vargas et al evaluated neoplastic lesions related to the brachial plexus in a limited number of patients.48 No significant difference was found in FA and ADC values between healthy individuals and those with tumors, or between benign and malignant tumors. However, malignant lesions were more likely to demonstrate fiber disruption on tractography images. Kasprian et al assessed the utility of DTI in identifying peripheral nerve infiltration in cases of soft tissue tumors in close proximity to peripheral nerves.49 In cases of malignant infiltration of peripheral nerves by adjacent soft tissue tumors, the researchers demonstrated either a change in caliber or a complete disruption of the nerve on tractography images. Moreover, they were able to localize the nerve on DTI images in cases of encasement by tumor or, in cases of peripheral nerve sheath tumors, even when the nerve was not well delineated on T2-weighted imaging.

References 1 Lerner A, Mogensen MA, Kim PE, Shiroishi MS, Hwang DH, Law M.

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DTI of Polyneuropathies In subjects with chronic inflammatory demyelinating polyneuropathy (CIDP), Kakuda et al showed a significant decrease in FA values of the tibial nerve compared with healthy controls.18 The FA values correlated with action potential amplitude but not nerve velocities. Mathys et al examined the sciatic nerve in subjects with CIDP and Guillain-Barré syndrome, as well as in healthy subjects.50 The researchers saw a significant reduction in FA in those with peripheral neuropathy but no significant change in other indexes. FA measurements correlated with functional scores, as well as compound muscle action potentials, but not other electrophysiologic variables.

Conclusion

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DTI is a promising technique for the evaluation of the microstructural properties of peripheral nerve and assessment of peripheral nerve pathology. However, the technique can be challenging, and it can be affected by poor SNR and artifacts. Although multiple studies have illustrated significant changes between healthy populations and subjects with peripheral neuropathies, there is significant overlap in DTI indexes between volunteers with disease and those who are healthy. A further drawback of the technique is that specific values for the various DTI indexes depend on the imaging technique and cannot be applied across populations and different imaging protocols. This could mean that normative values need to be established for each nerve based on local imaging protocols. In cases of localized mononeuropathy, it might be possible to compare DTI values along a nerve or between nerves in the same extremity as a diagnostic criterion, but further study is needed. These considerations limit

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its utility as a routine diagnostic tool in clinical practices, and, as such, it currently remains primarily a research tool.

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Seminars in Musculoskeletal Radiology

Vol. 19

No. 2/2015

199

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Diffusion Tensor Imaging of Peripheral Nerves

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Diffusion tensor imaging of peripheral nerves.

Diffusion tensor imaging (DTI) is a powerful MR imaging technique that can be used to probe the microstructural environment of highly anisotropic tiss...
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