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Hindawi Publishing CorporationRadiology Research and PracticeVolume 2013, Article ID 809568, 14 pageshttp://dx.doi.org/10.1155/2013/809568

Review ArticleMR Neurography: Advances

Avneesh Chhabra,1 Lianxin Zhao,2 John A. Carrino,1 Eo Trueblood,1 Saso Koceski,3

Filip Shteriev,4 Lionel Lenkinski,5 Christopher D. J. Sinclair,6 and Gustav Andreisek7

1 Musculoskeletal Radiology Section, Russell H Morgan Department of Radiology & Radiological Science,Johns Hopkins University Hospital, Baltimore, MD 21287, USA

2Department of MR, Shandong Medical Imaging Research Institute, Shandong University, China3Department of Intelligent Systems and Robotics, Faculty of Computer Science, University Goce Delcev Stip, 2000 Stip, Macedonia4 SyNRG Software & IT Solutions, Skopje, Macedonia5 3D Imaging Partners, Toronto, ON, Canada6MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology, University College London, Queen Square,London WC1N 3BG, UK

7Department of Radiology, University Hospital Zurich, Zurich, Switzerland

Correspondence should be addressed to Avneesh Chhabra; [email protected]

Received 18 June 2012; Accepted 3 February 2013

Academic Editor: Zehava Sadka Rosenberg

Copyright © 2013 Avneesh Chhabra et al. This is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properlycited.

High resolution and high field magnetic resonance neurography (MR neurography, MRN) is shown to have excellent anatomiccapability. There have been considerable advances in the technology in the last few years leading to various feasibility studies usingdifferent structural and functional imaging approaches in both clinical and research settings. This paper is intended to be a usefulseminar for readers who want to gain knowledge of the advancements in the MRN pulse sequences currently used in clinicalpractice as well as learn about the other techniques on the horizon aimed at better depiction of nerve anatomy, pathology, andpotential noninvasive evaluation of nerve degeneration or regeneration.

1. Introduction

High resolution and high field (3T) magnetic resonanceneurography (MR neurography, MRN) has been shown tohave excellent anatomic capability. This is in part due tothe rapid improvements in coil technology and software inthe last few years [1–3]. With improved detection of nerveanatomy and pathology, the value of quantitative functionalMR methods as potential biomarkers in neuromusculardisease is also being increasingly recognized [4]. Whilehigh resolution 2D (dimensional) and 3D demonstrationof peripheral nerve anatomy and pathology is the currentstate of the art, there have been considerable advances invarious aspects of the field leading to successful feasibilitystudies employing various structural and functional imagingtechniques in both clinical and research settings [1, 5–7].This paper is intended to be a useful seminar for readerswho want to gain knowledge of the advancements in the

MRN pulse sequences currently used in clinical practice aswell as learn about the other techniques on the horizonaimed at better depiction of nerve anatomy, pathology, andpotential noninvasive evaluation of nerve degeneration orregeneration.

2. Clinical Need for MR Neurography

It is estimated that about 5% of population has some formof neuropathy, and there is up to 5% incidence of peripheralnerve injuries in admissions to a level I trauma center [8, 9],with Sunderland grade I–IV injuries (nerve in continuity) farmore common than the grade V injury (nerve discontinuity).Clinical evaluation and electrodiagnostic studies provideincomplete information about the anatomy and degree ofinjury. In particular, these studies are not able to differentiateamong grade III–V injuries, which is important from a

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surgical point of view and patient prognosis [10, 11]. Manyof these patients undergo conservative management for 1-2years depending upon the clinical scenario. One has to oftenweigh the benefit versus risk of expectant waiting during thisperiod being cognizant of the fact that in the unfortunateevent of poor regenerative response and no recovery, theregional muscles will atrophy and tendon transfers as wellas consequent disability will be the only option left for thepatient with a poor outcome [12]. High field (3 Tesla, T)imaging employing high resolution MRN techniques is animportant noninvasive modality that can both detect as wellas help to grade nerve injuries [2, 13].

In the clinical arena, there is also an immediate need forreliable quantitative measures that can evaluate peripheralnerve regeneration/further degeneration in patients withtraumatic nerve injuries. Proximodistal axonal regenerationis the leading mechanism of recovery from nerve injuries.However, it occurs at a slow pace (∼1mm/day), and theonly available clinical tool of “advancing Tinel’s sign” isoften unreliable, subjective, and frequently inaccurate. Theelectrodiagnostic studies are also not sufficient due to theircomplete dependence on target innervation and lack ofinterobserver reliability [12]. Therefore, it is crucial for devel-opment of a technique that can detect the nerve continuityor neuroma and can be used serially in a noninvasivemanner to detect the initiation as well as follow the regen-eration in injured axons proximally and across the injurysite. Another immediate clinical and preclinical need fornoninvasive outcome measurement of nerve regeneration isin the area of therapeutics aiming to enhance nerve growth ininjuries and mono-/polyneuropathy conditions. Availabilityof reliable noninvasive techniques can facilitate clinical trialsusing nerve regeneration enhancers (neurotrophic agents),improvements in the development of nerve conduits withincorporated molecular biology agents, such as stem cells,proteins, and nanotechnology [14–16].

3. Three-Dimensional Anatomic NonselectiveMR Neurography

Three-dimensional (3D) anatomic MR imaging is not newand has been around for more than 2 decades. However,the latest 3D imaging techniques encompass high resolution(base resolution > 256 and in plane resolution ∼1mm) withsuperior T2 type contrast also available in some sequences.Additional advanced characteristics include absence of pul-sation artifacts and isotropic acquisition with multiplanarcapabilities leading to no or only little loss of tissue def-inition on secondary reformatted images. The addition ofrecently developed 3D imaging techniques to standard 2DMR imaging protocols helps to overcome difficulties such asimprecise lesion localization, tissue characterization, partialvolume artifacts, and overall image interpretation [1, 4, 13, 17].

These new 3D anatomic MR sequences are now possibledue to increased signal-to-noise ratio (SNR) of the high fieldMR scanners, improved coil design and prudent use of paral-lel imaging techniques. Parallel imaging helps achieve fasteracquisition, increased contrast resolution and/or number of

slices, better background fat suppression, and a reductionin the echo time/echo spacing, ultimately resulting in lessimage distortion [1, 17]. On current 3T MR scanners, 3Dimaging can be quickly obtained within 5-6 minutes depend-ing upon the field of view and isotropic resolution set inthe range of 0.9–1.5mm. With curved planar reformations(CPRs) and maximum intensity projections (MIPs), there isfurther reduction of noise, and the peripheral nerves can bebeautifully displayed along their long axis to demonstratethe nerve anatomy and pathology [18]. These sequences aretermed differently by various vendors as SPACE (samplingperfection with application optimized contrasts using vary-ing flip angle evolutions, Siemens), Cube (General ElectricHealthcare, Waukesha, WI), and VISTA (Philips, Best, TheNetherlands).The authors use SPACE imaging, which can beobtained with and without fat suppression and can generatevarious contrasts depending upon the clinical situation: T1,proton density (PD), T2, SPAIR (spectral adiabatic inversionrecovery), and STIR (short tau inversion recovery). The 3DSPAIR SPACE is used in extremities due to its higher SNR,3D STIR SPACE is used for plexuses due to better and morehomogeneous fat suppression, and 3D T2 SPACE is usedfor spine evaluation (also referred to as MR myelography)and for the evaluation of preganglionic nerve segments, asthey exit from the spinal cord (Figure 1). Three-dimensionalCISS (constructive interference in steady state) is anothertechnique available for high resolution cranial nerve and pre-ganglionic segment evaluation in the background of high-intensity CSF [19]. While 3D imaging does not currentlyreplace the 2D imaging (in plane resolution 0.4-0.5mm) forsmaller nerves, it is useful for multiplanar demonstrationof pathology to the referring physicians for presurgicalplanning (Figure 2) [13]. The 3D SPAIR SPACE and 3D STIRSPACE approaches require postprocessing to remove thehyperintense vessels and fluid containing structures, whichoften contaminate the field of view andmay lead to difficultiesin nerve visualization (Figures 3(a) and 3(b)).

4. Three-Dimensional AnatomicNerve-Selective MR Neurography

Nerve-selective MR imaging is aimed at suppressingthe vascular and/or fat signal to create unique tissue-selective images. These are especially useful for radiologistsand referring physicians who are not used to looking atperipheral nerve images on a routine basis. Such techniquesshould be incorporated in the MRN protocol wheneveraccurate nerve localization and/or presurgical assessment arerequired. There are various ways to create such images, withall techniques employing some sort of diffusion weighting.The peripheral nerves have a strong longitudinal order andorientation of structural components, leading to diffusionanisotropy. Thus, addition of diffusion weighting (DW)to the anatomic sequence (hybrid technique), or withpredominant use of a directionally encoded DW sequences,the technologist can easily generate selective longitudinalimages of the peripheral nerves due to the predominant andunrestricted longitudinal diffusivity of protons. One such

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Figure 1: (a) 3D anatomic nonselective MRN-MIP reconstruction from a coronal 3D STIR SPACE sequence shows normal symmetric signalintensity and size of bilateral brachial plexuses (arrows). (b) 3D anatomic nonselective MRN-MIP reconstruction from a coronal 3D STIRSPACE sequence shows normal symmetric signal intensity and size of bilateral LS plexuses and femoral nerves (arrows). (c) 3D anatomicnonselective MRN-Axial reconstruction from 3D T2 SPACE sequence shows the dorsal and ventral roots (preganglionic segments) on bothsides (arrows).

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Figure 2: (a) 2D versus 3D anatomic nonselective MRN-Axial T2 SPAIR image through the lower abdomen shows the abnormallyhyperintense left ilioinguinal nerve (arrows) in a suspected case of left ilioinguinal neuropathy. (b) 2D versus 3D anatomic nonselectiveMRN-MIP reconstruction from a coronal 3D STIR SPACE sequence barely shows the left ilioinguinal nerve (large arrows). Notice normalright ilioinguinal nerve (medium arrow) and normal bilateral femoral nerves (small arrows).

technique optimized by the author (AC) and is routinelyused at his institution is fat suppressed 3D DW PSIF(reversed fast imaging in steady state free precession) dueto its ability to produce nerve specific images with excellentvascular suppression (inherent low diffusion moment, 𝑏value ∼80 s/mm2) and fat suppression, while retaining allthe advantages of an isotropic 3D MR imaging technique

(Figure 3(c)). It should be noted that 3D DW PSIF is asensitive sequence; it is prone to motion and ghosting arti-facts. However, MIP reconstructions can enhance apparentSNR and be used to elegantly demonstrate nerves in multipleplanes (Figure 4) [3, 6, 20]. Since it is a steady state sequencewith both T1 and T2 contrasts, it shows neuropathy and masslesions as abnormal T2 hyperintensity, with normal nerves


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Figure 3: (a) Limitation of 3D anatomic nonselective MRN-Axial T2 SPAIR image through the upper calf shows amputation neuromasof tibial nerve (large arrow) and common peroneal nerve (small arrow). (b) Limitation of 3D anatomic nonselective MRN-Sagittalreconstruction from a 3D SPAIR SPACE sequence in the same case shows the abnormal tibial nerve in its long axis (smaller arrow) withan end-bulb neuroma (large arrow). However, there is suboptimal depiction due to hyperintense vascular signal contamination (mediumarrows). (c) 3D anatomic nerve selective MRN-Sagittal reconstruction from a 3D DW PSIF sequence in the same case selectively shows theabnormal tibial nerve in its long axis (small arrows) with an end-bulb neuroma (large arrow).

Figure 4: 3D anatomic nerve selective MRN-Multiplanar reconstructions from an isotropic 3D DW PSIF sequence through the mid footshows the normal long axis appearances of the medial plantar nerve (large arrows) and lateral plantar nerve (small arrow).

appearing isointense to muscles, similar to other anatomicspin echo type sequences. Additionally, it can also be usedbefore and after intravenous contrast and has potential toreplace traditional fat suppressed postcontrast T1W imaging.

Selective DW peripheral nerve imaging requires a higherdiffusion moment (𝑏 value ∼400–1200 s/mm2). It can beperformed with a unidirectional motion probing gradient (𝑏value ∼800 s/mm2) applied in anteroposterior direction inthe axial plane using single shot STIR echo planar imaging.The perpendicular positioning of the motion probing gradi-ent to the nerves offers the highest signal as the diffusion is

relatively more restricted across the nerve (Figures 5 and 6)[21]. Another recently described technique known as SUSHI(subtraction of unidirectionally encoded images for suppres-sion of heavily isotropic objects using an intermediate 𝑏value ∼400–500 s/mm2) depicts the peripheral nerves withrelative selectivity along their long axis by subtracting DWdatasets acquired in directions parallel and perpendicular tothe peripheral nerves using a pair of diffusion sensitizinggradients [22]. As opposed to diffusion tensor imaging (DTI),these images maintain relatively higher SNR due to a limitednumber of motion probing gradients (less than 3). The


Figure 5: 3D anatomic nerve selective MRN-Coronal MIP from a3D diffusion weighted single shot EPI (𝑏 value 800 s/mm2) showsthe symmetrical normal appearance of bilateral brachial plexuses(arrows).

Figure 6: 3D anatomic nerve selective MRN-Coronal MIP from a3Ddiffusionweighted single shot EPI (𝑏 value 800 s/mm2) shows theperipheral nerve sheath tumors originating from the right C5 nerveroot and the left upper trunk (arrows).

acquired data can be reconstructed using thick slab MIPsfollowed by grey scale window setting inversion to selectivelydepict the long trajectory of the nerves with decreased noiseconspicuity.TheMIPs are best performed using a soap bubbletechnique (Philips Healthcare) that uses a curved subvolumedata set [21, 22], which helps exclude overlapping structures.Although this method is useful for selective nerve depiction,we prefer 3D anatomic and hybrid 3D DW PSIF images overDW imaging as these are better for fascicular evaluation andregional neuromuscular assessment due to the higher SNRand resolution available on these techniques. Additionally,pre-ganglionic nerve segment assessment as well as evalua-tion of the nerves running parallel to themotion probing gra-dient are difficult to perform on DW imaging. Finally, bonesand lymph nodes show up as high signal on DW imaging andvessel contaminationmay still be present, leading to difficultyin nerve visualization, especially in the distal calf.

5. Three-Dimensional (3D) Functional NerveSelective Imaging

The anatomic techniques are good for the assessment ofneuropathy and worsening axonal degeneration; however, T2signal alterations are not proven to reliably assess the nerveregeneration after traumatic injuries or nerve surgery [24–26]. The need for more objective and noninvasive functional

measures of axonal regeneration in peripheral nerves isincreasingly recognized as new therapeutic targets are beingexplored and many novel interventions are entering thepreclinical stage of drug development. Three-dimensional(3D) functional nerve selective imaging can be performedusing diffusion tensor imaging (DTI), and results from initialfeasibility studies are becoming available [27–29].

DTI interrogates the random thermal motion of watermolecules within tissues along different axes. It can thereforebe used to exploit the potential of distinct microstructuralproperties of the peripheral nerves that hinder proton diffu-sion in some directions and facilitate it in other directions.DTI thus allows interrogation of the microarchitecture ofthe nerves, which is beyond the resolution of anatomicimaging techniques.This technique has proven clinical utilityin a number of brain and spinal cord studies. However,early feasibility data from peripheral nerve are becomingavailable in the last few years with encouraging results incarpal tunnel studies in humans and sciatic nerve stud-ies in animals [5, 27–29]. Generally, 6 or more diffusionencoding directions are required for DTI and commonly12–20 directions and several 𝑏 values (commonly 0, 500,1000 s/mm2) are used to obtain improved diffusion tensormaps. However, this may result in significantly reduced SNR(Figure 7). Poor fat saturation, image distortions, as well aseddy current and ghosting artifacts may limit image quality.Additionally, acquisition times increase predisposing theimaging tomotion artifacts.Three Tesla imagingwith parallelacquisition, imaging in the axial plane, and tighter echospacing enable highly resolved tensor maps. For peripheralnerves, higher 𝑏 values in the range of 800–1000 s/mm2and for plexuses, lower b values in the range of 600–800 s/mm2 generally produce adequate SNR and good qualitydatasets (Figure 8) [30]. However, the choice of the 𝑏 valueultimately depends on the field strength, coil, and receivertechnology.

DTI not only allows selective nerve visualization, but alsoenables quantitative measurement by creation of tractogra-phymaps.Themeasurements are fitted to a 3Ddiffusion ellip-soid tensor model [31, 32] which allows calculation of severalsemiquantitative parameters including the apparent diffusioncoefficient (ADC) and fractional anisotropy (FA). ADC is ascalar value that reflects molecular diffusivity under motionrestriction, and FA characterizes the directional variabilityin the diffusion, with an FA value of 0 representing randomisotropic diffusion and 1 representing complete anisotropy.Fiber tractography can be performed with a line propagationtechnique (linear tracking algorithm) in which a tracking lineis propagated from a start point (seed) placed perpendicularto the nerve in the principal diffusion direction.This methodexcludes the other false positive trajectories that may arisefrom anisotropic structures, such as the skeletal muscles. DTIcan be used to evaluate fiber density by displaying tracts oncolor-coded 3D images [28].

Normal nerve FA values range from 0.4–0.8 dependingon the SNR and type of nerve. However, the mean values ofthe normal nerves under interrogation are generally within2 standard deviations of the adjacent nerves or contralateral


Figure 7: 3D functional nerve selective MRN-Coronal MIP(inverted grey scale contrast) from a 3DDTI using single shot EPI (𝑏value 0, 800, 1000 s/mm2 and 12 directions of interrogation) showsthe symmetrical normal appearance of bilateral brachial plexuses(arrows). However, notice the decrease in SNR as compared todiffusion weighted imaging as shown in Figure 5.

equivalent nerves, and significant reductions of FA in abnor-mal nerves have been observed [27, 31]. Increased diffusivity,measured using the ADC, generally reflects inflammation,edema, or expanded nerve space, whereas decreased FAmay be caused by damaged tissue microstructure, axonalloss and/or demyelination, or increase in isotropic watervolume. Therefore, decreasing FA values is expected withworsening neuropathy. In a study by Takagi et al., the FAvalues decreased at the site of injury immediately followingthe insult and distally along the nerve 4 days after the injury.Additionally, increased FA values were observed at 3 weeksafter injury correlating with functional motor and sensoryrecovery as well as nerve regeneration [7]. The previousauthors found that the FA alterations of the peripheralnerves weremore strongly correlatedwith axon-related (axondensity and diameter) than with myelin-related (myelindensity and thickness) parameters, supporting the theory thataxonal membranes play a major role in anisotropic waterdiffusion and that myelination can modulate the degree ofanisotropy. Tractography based on FA values also showedloss of fiber tracking distal to the crush site at earlier timepoints, and recovery of fiber tracking was noted at latertime points related to axonal regeneration. In another sciaticnerve crush model, Lehmann et al. also found that FAvalues are a more useful parameter than diffusivity in theassessment of axonal regeneration [33]. In a recent carpaltunnel syndrome (CTS) case-control study, the FA, radialdiffusivity, and ADC differed significantly between healthysubjects and CTS patients. DTI indices differed in regionsproximal to and within the carpal tunnel in a manner whichseemed to appropriately reflect pathophysiology of CTS [34].

ADC values also help differentiate among benign andmalignant tumors. Higher ADC values are seen withbenign peripheral nerve sheath tumors and other soft tissuetumors (1.1–2.0 × 10−3mm2/s), while low diffusivity values(0.7–1.0 × 10−3mm2/s) are seen in malignant lesions (Fig-ure 9) [35]. We presently use 3 cutoffs for their clinical prac-tice currently (ADC—< 1.0 × 10−3mm2/s—suspicious formalignancy, ADC—1.0–1.5 × 10−3mm2/s—indeterminate,ADC—> 1.5 × 10−3mm2/s—usually benign.) However, theADC values should complement the conventional imagingappearances of these lesions, and one should not read themin isolation. Secondly, the reader should focus on the lowest

Figure 8: 3D functional nerve selective MRN-Coronal MIP(inverted grey scale contrast) from a 3D DTI using single shot EPI(𝑏 values 0, 600 s/mm2 and 20 directions of interrogation) shows thesymmetrical enlargement of bilateral LS plexus nerve roots (arrows)in a known case of hereditary motor and sensory neuropathy withdiffusely reduced FA values in bilateral nerves.

ADC of the lesion, which correlates with the cellularity ofthe lesion, since even malignant lesions can have higherADC values in their necrotic/less cellular portions. Thelower ADC areas also correlate with the highest F18 FDGPET uptake regions and solid nodular arterial enhancingareas of the tumors, which helps in locating the mostcellular areas for biopsy (Figure 10). It should also be keptin mind that interval measurements over time are moreuseful than a one-time measurement. This helps to followthe lesions, while patient is on medical treatment, such asimatinib. Increasing ADC values generally correlates withtumor response; however, it remains to be seen if they addmore value over contrast imaging. But, as initial resultsare becoming available, MRN with DTI promises to be asingle shot modality for the evaluation of peripheral nervesheath tumors. Finally, tractography provides another insightinto the pathophysiologic mechanisms of the lesions arisingwithin or in close relationship to the directionally orderednerve fibers. The degree of nerve tract disruption potentiallycorrelates with increased aggressiveness/malignancy of thelesion and gives the surgeon an idea about potential fascicularinfiltration of the tumor cells and difficulty in resection,which can be foreseen before the operation and is currentlybeyond the capability of anatomic images [1, 28].

DTI provides a unique opportunity to evaluate thecomplex diffusion patterns that occur within the nerve andallows understanding of pathophysiologic mechanisms in a3Dmanner although some limitations need to be understood.DTI is a sensitive sequence, prone to motion and ghostingartifacts. Although peripheral nerves have a simpler archi-tecture than the central nervous system and tractographyshould be easier to perform, DTI usually suffers from therelatively short T2 of water protons in the nerves leading topoor SNR.The variations in image quality or DTI parametersmay significantly degrade serial assessment of parametric


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Figure 9: (a) Combined anatomic and functional MRN-MIP reconstruction from a 3D STIR SPACE sequence shows abnormal fusiformenlargement of the right S1 nerve root by a benign peripheral nerve sheath tumor (large arrows). Notice the normal appearance of thecontralateral S1 nerve root (small arrow). (b) Combined anatomic and functional MRN-ADC map from single shot EPI DTI (𝑏 value 0,600 s/mm2 and 20 directions) sequence shows highADCvalue (1.4×10−3mm2/s). (c) Combined anatomic and functionalMRN-Tractographymap following tensor calculation from single shot EPI DTI sequence shows nearly normal tracts (arrow) through the mass lesion in keepingwith benign nature of the lesion.

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Figure 10: (a) Anatomic MRN, functional MRN, and F-18 FDG-PET correlation-Coronal fat suppressed postcontrast 3D T1W image of abiopsy proven malignant peripheral nerve sheath tumor shows the solid heterogeneous enhancement along the superior aspect of the lesion(large arrow). Notice additional smaller benign PNSTs in this case of neurofibromatosis type I (small arrows). (b) AnatomicMRN, functionalMRN, and F-18 FDG-PET correlation-Coronal MIP reconstruction (inverted grey scale contrast) from single shot DTI (𝑏 values 0, 800,1000 s/mm2, 12 directions) image shows the lowest ADC values (0.7×10−3mm2/s) along the superior aspect of the lesion, which was targetedfor the successful biopsy (large arrow). Notice that the additional smaller benign PNSTs showhigher ADCvalues (small arrows). (c) AnatomicMRN, functional MRN, and F-18 FDG-PET correlation-Coronal F-18 FDG image shows high SUV max value (4 increased to 6 on delayedimage) in the corresponding superior aspect of the lesion.


values and tensor maps. Maintaining the same acquisitionparameters on serial scans, the application of good uniformfat suppression (water selective/Dixon/STIR), parallel imag-ing, keeping the slice thickness at or above 4mm, employinghigher strength gradients, lower echo times, and tighterecho spacing each help to generate acceptable images withadequate spatial resolution and reproducible tractography.The reader should understand that DTI is still at a feasibilityassessment stage and is limited by relative lack of stan-dardization and complexity of post-processing techniques.The preliminary ADC and FA data among different subjectsshow high (274%) variability. However, one could use healthycontralateral nerve as an internal control, since there isabsence of statistically significant intrasubject side-to-sidevariability in quantitative data [29].

Fixed points of measurements based on bony landmarksshould be used for quantitative measurements to mitigatevariability, and the applied regions of interest should besmall to avoid partial volume artifacts and large enough tocover the representative area of the nerve. Finally, the readershould understand that axonal loss injury also results inmyelin loss over time, and the exact relative contributionsof the two pathological conditions to the DTI parametersmeasured are not clearly known. With future research, DTIwill likely play an important role in the evaluation and furtherunderstanding of neuromuscular diseases and is expectedto be an important complement to current anatomic MRNprotocols.

6. Magnetization Transfer (MT) Imaging

MT imaging provides information about in vivo tissueintegrity by exploiting differences in the properties of freewater protons and restricted protons that are bound tomacromolecules, proteins, and cell membranes. The boundprotons in peripheral nerve include collagen, myelin, andmembranes contained in the nerve fibers.The bound protonshave a T2 relaxation time too short to be detected by conven-tional MR imaging techniques. However, MT imaging offersindirect characterization of the bound proton componentand might provide information about nerve damage anddemyelination in peripheral neuropathy. Selective saturationof the bound pool can be achieved with an applied offresonance radiofrequency pulse and when combined witha 3D spoiled gradient-echo image readout may be used togenerate additional contrast on conventionalMR images.Thesemiquantitative MT ratio (MTR) may also be calculated bycomparing the signal reduction of an MT-weighted imagerelative to an image without MT saturation [36].

In isotropic fluid compartments such as the cerebrospinalfluid (CSF), where a negligible concentration of macro-molecules is present, the MTR is close to zero. In studiesof multiple sclerosis, a decrease of MTR baseline valueshas been observed to correlate with demyelination, edema,and/or tissue damage in the brain [37]. In a study of opticneuropathy, MTR was reduced in affected nerves comparedto clinically unaffected nerves [23]. Retinal neuroaxonal lossalso correlated with MTR. Since axonal loss following optic

neuritis also results in myelin loss, the relative contributionsof the two pathological conditions to the MTR measurescould not be evaluated. In a recent study of healthy volunteers,Gambarota et al. observed significant differences in the MTRof foot nerves versus median nerves; however, the regionalmuscles showed no significant differences [36]. MT imagingof muscle tissue has shown promise in neuropathic diseasesincluding diabetic foot neuropathy, chronic inflammatorydemyelinating polyneuropathy (CIDP), and Charcot MarieTooth (CMT) disease (Figure 11), where decreased MTR isobserved in muscles affected by these diseases as well as inmuscle conditions including limb girdle muscular dystrophy[23, 38–41]. More research on MT imaging in peripheralneuropathy is needed, and its value for evaluation of muscledenervation compared with STIR and DW imaging needs tobe proven before it can be used in the routine clinical setting.MT imaging has limitations that include a typically highsequence specific absorption rate (SAR) and a dependence ofthe measured MTR values on the specific sequence param-eters used. Quantitative measurements in nerve present aparticular challenge because of the requirement for highspatial resolution and SNR.

7. Muscle Imaging

MR can demonstrate regional muscle denervation changesin addition to the direct signs of nerve abnormality. Thesemuscle findings evolve from edema like signal on fat sup-pressed T2WMR images in acute stages to fatty replacementand atrophywith chronicity [18, 42]. Although the prognosticfactors affecting the outcome of nerve repair vary dependingupon the degree of nerve injury and other clinical factors,such as age, patient’s expectation, and surgeon’s experience,fatty replacement and atrophy of the regional muscles is oneof the important and measurable factors negatively influenc-ing functional and anatomic outcomes [12, 43]. In addition toDTI and MT imaging mentioned earlier, a number of otherfunctional MR imaging tools are available for assessment ofregional muscle architecture and perfusion such as MR spec-troscopy (MRS), C13 hyperpolarized imaging, or multiechoimaging for fat fraction assessment, chemical shift imaging(CSI), as well as ASL (arterial spin labeling) andBOLD (bloodlevel oxygenation determination) imaging. Research is underway using these technologies at various centers looking atdifferent functional and pathophysiologic mechanisms ofthe neuromuscular disease [44–48]. Despite the advantageof MR imaging in detecting muscle morphology changes,biochemistry, and pathology combined with the potential toinfluence the way surgeons approach and treat nerve injurypatients, there is currently paucity of research or literature onthis subject on how it would affect clinical decision making.

8. Whole Body MRN

Whole body MR imaging has been around for many yearsfor the evaluation of metastatic disease, myeloma, and lym-phoma. Takahara et al. described a free breathing DW wholebody MR imaging technique with background body signal


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Figure 11: (a) MT neurography imaging of the sciatic nerve- Magnetization transfer ratio map at the mid-thigh level. Inset: enlargement ofthe sciatic nerve demonstrates measurable MTR effect in the nerve. (b) MTmuscle imaging of neuropathy. Magnetization transfer ratio mapof the mid-calf muscles of a patient with Charcot-Marie-Tooth disease type 1A (CMT1A).TheMTR is reduced in areas affected by pathology.The maps have been corrected for RF inhomogeneities with a compensation method using B1 transmit maps [23].

suppression and an STIR prepulse for robust fat suppression,which enables a longer effective imaging time than that withbreath-hold imaging and allows acquisition of a large numberof thin sections and three-dimensional analyses.This allowedsignal decrease from intravoxel incoherent motion and notfrom respiratory motion (coherent motion) during the shorttime (approximately 100ms) that motion-probing gradientsare applied [49].Whole bodyMR imaging using 3D isotropicSTIR SPACE is also being performed with success at ourinstitute [50]. Whole body MRN using simple diffusionweighted imaging was reported by Yamashita et al. in 2009[51]. However, using a combination of thin collimation(1.5mm isotropic) high contrast 3D STIR SPACE and DTI,whole body MRN can be performed in acceptable timeperiods of less than 45min to 1 hour by employing parallelimaging technique (iPat factor: 2–4) with coverage fromthe skull base to the level of the knees in our preliminaryexperience, and feasibility studies are being performed usingthis technology (Figure 12). Adding DTI of the plexuses tothe anatomic imaging represents a considerable advance inimaging and holds promise in assessment of disease burdenand treatment response in neurocutaneous syndromes,CIDP, and hereditary neuropathies, such as CMT disease.This technique allows thin section reconstruction in anydesired plane, avoids partial volume artifacts, and can easilydetect thickened nerves or related mass lesions. Additionally,DTI of plexuses may be used for functional evaluation, andsimilar techniques could be used for followups on treatmentor on finding worsening neuropathy.

9. Contrast Agents and Other Imaging Agents

The application of intravenous gadolinium-based contrastagents is currently limited in MRN studies to examinationsperformed for indications of infection, inflammation andneoplastic conditions (Figure 10) [2, 13, 20, 26]. Two differentexogeneous intravenous contrast agents have been tried

in evaluation of peripheral neuropathy. These includesuperparamagnetic iron oxide (SPIO) and gadoflouride M[52–54]. Gadoflouride M (GFM) is a nerve-selective contrastagent, which in animal studies has been shown to accumulatein nerve fibers undergoing Wallerian degeneration anddisappear with remyelination. However, GFM has toundergo various research trials and human safety testingbefore it can receive FDA approval or can be used in clinicalsetting. Additionally, difficulty in visualizing axons makesthese methods impractical for evaluating peripheral nerveinjury in the present clinical scenario. Finally, molecularagents, such as stem cells, proteins, and nanoparticlesunder development can be potentially infused to selectivelyenhance/image nerve regeneration and hold considerablepromise in the advancement of the field [14–16, 55].

10. Testing the Significance of NerveAbnormality Causing Symptoms

There are various ways to test whether the nerve itselfor an associated imaging abnormality such as neuroma isthe potential cause of patient symptoms. This could bedone by ultrasound guided (USG) injections for super-ficial nerves and MR guided injection for the deeplylocated/nonidentifiable nerves on other imaging techniques(Figure 13). Although image guided injections have high facevalidity and are good for therapeutic effect, any diagnosticinjection should ideally follow a protocol of comparative,graded, or placebo controlled injections to be accurate andvalid [56, 57]. Another tool that may become available infuture is high intensity focused ultrasound, which is shown toreliably induce sensations in human test subjects in a mannerthat correlates with their mechanoreceptor density [58].

11. Teaching and Web Tools

With excellent imaging of peripheral nerve anatomy andpathology available with current techniques and functional


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(b)

(c) (d)

Figure 12: (a), (b) Whole body MRN: Coronal MIP reconstructions from 3D STIR SPACE sequence ((a) conventional window setting; (b)inverted window setting) show the normal appearance of bilateral brachial plexus (large arrows), LS plexus (medium arrows), and sciaticnerves (small arrows). (c), (d) Whole bodyMRN: Coronal MIP reconstructions (inverted grey scale contrast) from single shot DTI sequence(𝑏 values 0, 600 s/mm2, 20 directions) of the brachial plexus (c) and LS plexus (d).

evaluation becoming possible, it is important for the radi-ologist to gain knowledge of the complex peripheral ner-vous system anatomy and its normal as well as abnormalimaging appearances. Also, with widespread use of high-resolution MRN imaging, various small and large nervebranches can be visualized. An experienced observer caneasily find them; however, the complex anatomy can bedifficult to navigate through for those not used to lookingat these tiny peripheral branches. Existing illustrations arelimited in their effectiveness due to previous technology,illustration technique, and limitations of education media.Increasingly, text books and journals are being replaced bydigital interactive media. For this reason, it is important tosuperimpose anatomic illustrations over the MRN imagesand develop a digital platform for their demonstration to keep

in stride with the advancements of science and education.With tandem depiction of sequential axial 2D MRN and 3DMRN images and original custom illustrated images withnerve labeling, the entirety of the peripheral nerve can beillustrated. Once integrated with the web tools, a readercan use them for their learning, correct nerve identificationand MRN interpretation (Figure 14). Such an idea has beenenvisioned by the authors, and it is conceivable that it willlikely become a useful web tool in few years to come.

12. Nerve Segmentation

Although appropriate performance of MRN using 3D imag-ing and the correct interpretation of the nerve findings is


(a) (b)

(c) (d)

Figure 13: (a)–(d) MRN guided intervention-Axial T2 SPAIR (a), PDW (b), STIR (c), and T2 SPACE (d) images obtained during injectionof local anesthetic and steroid combination around the right ilioinguinal nerve (arrow in a), beneath the external oblique aponeurosis. Thepatient experienced no significant pain relief following the injection in keeping with a negative block.

Figure 14: Anatomic illustration usingMRN-Axial T2 SPAIR imagethrough the upper pelvis with color drawing overlay nicely depictingthe pelvic neuromuscular anatomy.

essential, it is also important to display the nerve anatomyand pathology to surgeons in a longitudinal manner, as theyare used to seeing them during surgical dissection. Nervesegmentation allows longitudinal depiction of the peripheralnerves in multiple planes but also avoids contamination fromthe adjacent bright vessels and displays nerve architecturalvariations (bifid, trifid, or split). Most readers use axialimages for primary detailed assessment of the nerves. Atool which can reconstruct the nerves in longitudinal planesby placing the regions of interest on the axial images,where these are best and reliably identified, would also

help solve the issues encountered in the nerve identifica-tion, and depiction along its long axis and help diagnosisof displacement/entrapment/impingement by demonstratingalterations in the course as well as caliber of the nerves. Cus-tom made software such as “Nerve Vision” will be availablein future, which allows DICOM image import as well asnavigation by implementing a semi-automatic segmentationalgorithm consisting of two main steps. First, the user startsthe segmentation of the object by interactively placing fewcontrol points at the nerve’s border (not necessarily locatedon local maximal or most significant gradients). Second,these points are connected to an initial polygonal contourconsisting of an order set of vertices. The algorithm thenevolves a 3D polygonal contour that is as similar as possibleto the landmarks in its behavior. In addition to the image-based attributes, the algorithm maintains the smoothness ofthe contour throughout the course of the nerve to ensurerobust segmentation results. Additionally, in order to help theuser best understand the volume data and to uncover impor-tant details in the volume data, the software implements areal-time visualization method based on GPU ray casting,which is capable of using multiple planes for convex volumeclipping. This approach allows the user to select arbitrarynumber of clipping planes. This novel approach to 3D nervesegmentation of the peripheral nerves in the axial planesusing semiautomated interactive algorithmsprovides realistic


Figure 15: Nerve segmentation-Median nerve segmentation using custom made software. The tool allows semiautomated nervesegmentation, while a user draws region of interest on the nerve on sequential axial images.

3D visualization of the long axis of the nerve. This can beuseful for identification, visualization of position, and forfinding displacement/impingement and caliber variations ofthe nerve, as well as to track the nerve propagation throughthe confined spaces (tunnels) (Figure 15).

To conclude, there have been considerable advances inthe field of MR neurography making it a fruitful area forresearchers to exploit the potential of a range of techniquescurrently available for imaging nerve and regionalmuscle andto assess their function in both research and clinical settings.

Disclosure

A. Chhabra acknowledges the support of GE-AUR, SiemensMedical Solutions, Gatewood fellowship award, and IntegraLife Sciences. A. Chhabra also serves as consultant forSiemens MSK CAD system development. J. A. Carrinoprovides consulting services for Quality Medical Metrics,serves on boards for General Electric and Vital Images,has received grants from Siemens, Toshiba, and Carestream,and lectures for Siemens. G. Andreisek was co-worker of astudy for which a US patent was applied (USPTO Number12/947,256); received grants from Swiss National ScienceFoundation (SNCF), Holcim, and Siemens; is Co-PI or Sub-PI in several third party funded clinical trials at theUniversityof Zurich (Sponsors include: Millennium Pharmaceuticals,Eli Lilly, GlaxoSmithKline, Cytheris SA, Roche, BioChemics,Novartis, Bristol-Meyers Squibb, TopoTarget, and MerckSharp & Dohme). The department Gustav Andreisek worksfor receives grants from Bayer, GE, Phillips, Cordis, andGuerbet. Gustav Andreisek has given talks at a congresswhich was sponsored byMepha Pharma AG, Switzerland. Healso gave talks at Lunch symposia and CME courses whichwere organized and sponsored by Guerbet.

Acknowledgments

C. D. J. Sinclair is grateful to Dr. Jasper Morrow, Dr. JohnThornton, and theMRCCentre forNeuromuscularDiseases.

References

[1] M. Viallon, M. I. Vargas, H. Jlassi, K. O. Lovblad, and J.Delavelle, “High-resolution and functional magnetic resonanceimaging of the brachial plexus using an isotropic 3D T2STIR (Short Term Inversion Recovery) SPACE sequence anddiffusion tensor imaging,” European Radiology, vol. 18, no. 5, pp.1018–1023, 2008.

[2] A. Chhabra, E. H. Williams, K. C. Wang, A. L. Dellon, and J. A.Carrino, “MR neurography of neuromas related to nerve injuryand entrapment with surgical correlation,” American Journal ofNeuroradiology, vol. 31, no. 8, pp. 1363–1368, 2010.

[3] Z. Zhang, L. Song, Q. Meng et al., “Morphological analysisin patients with sciatica: a magnetic resonance imaging studyusing three-dimensional high-resolution diffusion-weightedmagnetic resonance neurography techniques,” Spine, vol. 34, no.7, pp. E245–E250, 2009.

[4] A. Chhabra, G. Andreisek, T. Soldatos et al., “MR neurography:past, present, and future,” American Journal of Roentgenology,vol. 197, pp. 583–591, 2011.

[5] R. Guggenberger, P. Eppenberger, D. Markovic et al., “MRneurography of the median nerve at 3. 0T: optimization ofdiffusion tensor imaging and fiber tractography,” EuropeanJournal of Radiology, vol. 81, no. 7, pp. e775–e782, 2012.

[6] A.Chhabra, T. Soldatos, T.K. Subhawong et al., “The applicationof three-dimensional diffusion-weighted PSIF technique inperipheral nerve imaging of the distal extremities,” Journal ofMagnetic Resonance Imaging, vol. 34, no. 4, pp. 962–967, 2011.

[7] T. Takagi, M. Nakamura, M. Yamada et al., “Visualization ofperipheral nerve degeneration and regeneration: monitoringwith diffusion tensor tractography,” NeuroImage, vol. 44, no. 3,pp. 884–892, 2009.


[8] J. D. England and A. K. Asbury, “Peripheral neuropathy,” TheLancet, vol. 363, no. 9427, pp. 2151–2161, 2004.

[9] C. N.Martyn and R. A. C. Hughes, “Epidemiology of peripheralneuropathy,” Journal of Neurology Neurosurgery and Psychiatry,vol. 62, no. 4, pp. 310–318, 1997.

[10] H. J. Seddon, P. B.Medawar, andH. Smith, “Rate of regenerationof peripheral nerves in man,”The Journal of Physiology, vol. 102,pp. 191–215, 1943.

[11] S. Sunderland, “A classification of peripheral nerve injuriesproducing loss of function,” Brain, vol. 74, no. 4, pp. 491–516,1951.

[12] K. A. Sheikh, “Non-invasive imaging of nerve regeneration,”Experimental Neurology, vol. 223, no. 1, pp. 72–76, 2010.

[13] A. Chhabra and G. Andreisek, Magnetic Resonance Neurogra-phy, chapter 3, Jaypee, Delhi, India, 1st edition, 2011.

[14] Z. Ren, Y. Wang, J. Peng, Q. Zhao, and S. Lu, “Role of stemcells in the regeneration and repair of peripheral nerves,”NatureReviews Neuroscience, vol. 23, no. 2, pp. 135–143, 2012.

[15] S. Nichterwitz, N. Hoffmann, R. Hajosch, S. Oberhoffner,and B. Schlosshauer, “Bioengineered glial strands for nerveregeneration,” Neuroscience Letters, vol. 484, no. 2, pp. 118–122,2010.

[16] U. Mittnacht, H. Hartmann, S. Hein et al., “Chitosan/siRNAnanoparticles biofunctionalize nerve implants and enable neu-rite outgrowth,”NanoLetters, vol. 10, no. 10, pp. 3933–3939, 2010.

[17] M. I. Vargas, M. Viallon, D. Nguyen, J. Y. Beaulieu, J. Delavelle,and M. Becker, “New approaches in imaging of the brachialplexus,” European Journal of Radiology, vol. 74, no. 2, pp. 403–410, 2010.

[18] A. Chhabra, P. P. Lee, C. Bizzell, and T. Soldatos, “3 Tesla MRneurography—technique, interpretation, and pitfalls,” SkeletalRadiology, vol. 40, pp. 1249–1260, 2011.

[19] R. Gasparotti, S. Ferraresi, L. Pinelli et al., “Three-dimensionalMR myelography of traumatic injuries of the brachial plexus,”American Journal of Neuroradiology, vol. 18, no. 9, pp. 1733–1742,1997.

[20] A. Chhabra, T. K. Subhawong, C. Bizzell, A. Flammang, andT. Soldatos, “3T MR neurography using three-dimensionaldiffusion-weighted PSIF: technical issues and advantages,”Skeletal Radiology, vol. 40, no. 10, pp. 1355–1360, 2011.

[21] T. Takahara, J. Hendrikse, T. Yamashita et al., “Diffusion-weighted MR neurography of the brachial plexus: FeasibilityStudy,” Radiology, vol. 249, no. 2, pp. 653–660, 2008.

[22] T. Takahara, T. C. Kwee, J. Hendrikse et al., “Subtraction ofunidirectionally encoded images for suppression of heavilyisotropic objects (SUSHI) for selective visualization of periph-eral nerves,” Neuroradiology, vol. 53, no. 2, pp. 109–116, 2011.

[23] S. A. Trip, P. G. Schlottmann, S. J. Jones et al., “Optic nervemagnetization transfer imaging andmeasures of axonal loss anddemyelination in optic neuritis,”Multiple Sclerosis, vol. 13, no. 7,pp. 875–879, 2007.

[24] A. T. Dailey, J. S. Tsuruda, A. G. Filler, K. R. Maravilla, R.Goodkin, and M. Kliot, “Magnetic resonance neurography ofperipheral nerve degeneration and regeneration,” The Lancet,vol. 350, no. 9086, pp. 1221–1222, 1997.

[25] G. A. Grant, G. W. Britz, R. Goodkin, J. G. Jarvik, K. Maravilla,and M. Kliot, “The utility of magnetic resonance imaging inevaluating peripheral nerve disorders,” Muscle and Nerve, vol.25, no. 3, pp. 314–331, 2002.

[26] A. G. Filler, F. A. Howe, C. E. Hayes et al., “Magnetic resonanceneurography,”The Lancet, vol. 341, no. 8846, pp. 659–661, 1993.

[27] A. Tagliafico, M. Calabrese, M. Puntoni et al., “Brachial plexusMR imaging: accuracy and reproducibility of DTI-derivedmeasurements and fibre tractography at 3. 0-T2011,” EuropeanRadiology, vol. 21, no. 8, pp. 1764–1771, 2011.

[28] A. Mallouhi, W. Marik, D. Prayer, F. Kainberger, G. Bodner,and G. Kasprian, “3 T MR tomography of the brachial plexus:structural and microstructural evaluation,” European Journal ofRadiology, vol. 81, no. 9, pp. 2231–2245, 2012.

[29] G. Andreisek, L. M. White, A. Kassner, and M. S. Sussman,“Evaluation of diffusion tensor imaging and fiber tractographyof the median nerve: preliminary results on intrasubject vari-ability and precision of measurements,” American Journal ofRoentgenology, vol. 194, no. 1, pp. W65–W72, 2010.

[30] A. Kido,M. Kataoka, A. Yamamoto et al., “Diffusion tensorMRIof the kidney at 3.0 and 1.5 Tesla,” Acta Radiologica, vol. 51, no.9, pp. 1059–1063, 2010.

[31] G. Andreisek, L. M. White, A. Kassner, G. Tomlinson, and M.S. Sussman, “Diffusion tensor imaging and fiber tractographyof the median nerve at 1.5T: optimization of b value,” SkeletalRadiology, vol. 38, no. 1, pp. 51–59, 2009.

[32] C. Khalil, J. F. Budzik, E. Kermarrec, V. Balbi, V. Le Thuc,and A. Cotten, “Tractography of peripheral nerves and skeletalmuscles,” European Journal of Radiology, vol. 76, no. 3, pp. 391–397, 2010.

[33] H. C. Lehmann, J. Zhang, S. Mori, and K. A. Sheikh, “Diffusiontensor imaging to assess axonal regeneration in peripheralnerves,” Experimental Neurology, vol. 223, no. 1, pp. 238–244,2010.

[34] D. Stein, A. Neufeld, O. Pasternak et al., “Diffusion tensorimaging of the median nerve in healthy and carpal tunnelsyndrome subjects,” Journal ofMagnetic Resonance Imaging, vol.29, no. 3, pp. 657–662, 2009.

[35] A. Chhabra, R. S. Thakkar, A. Gustav et al., “Anatomic MRimaging and functional diffusion tensor imaging of peripheralnerve tumor and tumor like conditions,” American Journal ofNeuroradiology. In press.

[36] G. Gambarota, G. Krueger, N. Theumann, and R. Mekle,“Magnetic resonance imaging of peripheral nerves: differencesin magnetization transfer,” Muscle & Nerve, vol. 45, no. 1, pp.13–17, 2012.

[37] T. Button, D. Altmann, D. Tozer et al., “Magnetization transferimaging in multiple sclerosis treated with alemtuzumab,” Mul-tiple Sclerosis, vol. 19, no. 2, pp. 241–244, 2013.

[38] P. D. Brash, J. Foster, W. Vennart, P. Anthony, and J. E.Tooke, “Magnetic resonance imaging techniques demonstratesoft tissue damage in the diabetic foot,” Diabetic Medicine, vol.16, no. 1, pp. 55–61, 1999.

[39] C. D. J. Sinclair, J. M. Morrow, M. G. Hanna et al., “Correctingradiofrequency inhomogeneity effects in skeletal muscle mag-netisation transfer maps,” NMR in Biomedicine, vol. 25, no. 2,pp. 262–270, 2012.

[40] J. D. McDaniel, J. L. Ulmer, R. W. Prost et al., “Magnetizationtransfer imaging of skeletal muscle in autosomal recessivelimb girdle muscular dystrophy,” Journal of Computer AssistedTomography, vol. 23, no. 4, pp. 609–614, 1999.

[41] C. D. Sinclair, J.M.Morrow,M. A.Miranda et al., “Skeletal mus-cle MRI magnetisation transfer ratio reflects clinical severity inperipheral neuropathies,” Journal of Neurology, Neurosurgery &Psychiatry, vol. 83, no. 1, pp. 29–32, 2012.

[42] K. R. Maravilla, B. D. L. Aagaard, and M. Kliot, “MR Neurog-raphy: MR imaging of peripheral nerves,” Magnetic ResonanceImaging Clinics of North America, vol. 6, no. 1, pp. 179–194, 1998.


[43] K. Rowshan, S. Hadley, K. Pham, V. Caiozzo, T. Q. Lee,and R. Gupta, “Development of fatty atrophy after neurologicand rotator cuff injuries in an animal model of rotator cuffpathology,” Journal of Bone and Joint Surgery A, vol. 92, no. 13,pp. 2270–2278, 2010.

[44] T. A. Bley, O. Wieben, C. J. Francois, J. H. Brittain, and S. B.Reeder, “Fat and water magnetic resonance imaging,” Journal ofMagnetic Resonance Imaging, vol. 31, no. 1, pp. 4–18, 2010.

[45] C. Boesch, J. Machann, P. Vermathen, and F. Schick, “Role ofproton MR for the study of muscle lipid metabolism,” NMR inBiomedicine, vol. 19, no. 7, pp. 968–988, 2006.

[46] C. Boesch, “Musculoskelatal spectroscopy,” Journal of MagneticResonance Imaging, vol. 25, no. 2, pp. 321–338, 2007.

[47] M. D. Noseworthy, A. D. Davis, and A. H. Elzibak, “AdvancedMR imaging techniques for skeletal muscle evaluation,” Semi-nars in Musculoskeletal Radiology, vol. 14, no. 2, pp. 257–268,2010.

[48] N. Saupe, L. M. White, M. S. Sussman, A. Kassner, G. Tom-linson, and M. D. Noseworthy, “Diffusion tensor magneticresonance imaging of the human calf: comparison between 1.5t and 3.0 t-preliminary results,” Investigative Radiology, vol. 43,no. 9, pp. 612–618, 2008.

[49] T. Takahara, Y. Imai, T. Yamashita, S. Yasuda, S. Nasu, andM. Van Cauteren, “Diffusion weighted whole body imagingwith background body signal suppression (DWIBS): technicalimprovement using free breathing, STIR andhigh resolution 3Ddisplay,” Radiation Medicine—Medical Imaging and RadiationOncology, vol. 22, no. 4, pp. 275–282, 2004.

[50] A. Chhabra and J. Blakely, “Whole-body imaging in schwanno-matosis,” Neurology, vol. 76, no. 23, article 2035, 2011.

[51] T. Yamashita, T. C. Kwee, and T. Takahara, “Whole-bodymagnetic resonance neurography,”The New England Journal ofMedicine, vol. 361, no. 5, pp. 538–539, 2009.

[52] C. Wessig, M. Bendszus, and G. Stoll, “In vivo visualization offocal demyelination in peripheral nerves by gadofluorine M-enhanced magnetic resonance imaging,” Experimental Neurol-ogy, vol. 204, no. 1, pp. 14–19, 2007.

[53] M. Bendszus, C. Wessig, A. Schutz et al., “Assessment ofnerve degeneration by Gadofluorine M-enhanced magneticresonance imaging,”Annals of Neurology, vol. 57, no. 3, pp. 388–395, 2005.

[54] M. Bendszus andG. Stoll, “Caught in the act: in vivomapping ofmacrophage infiltration in nerve injury by magnetic resonanceimaging,” Journal of Neuroscience, vol. 23, no. 34, pp. 10892–10896, 2003.

[55] C. Witzel, C. Rohde, and T. M. Brushart, “Pathway samplingby regenerating peripheral axons,” Journal of ComparativeNeurology, vol. 485, no. 3, pp. 183–190, 2005.

[56] A. J. R.Macfarlane, B. D. Sites, V. R. Sites et al., “Musculoskeletalsonopathology and ultrasound-guided regional anesthesia,”HSS Journal, vol. 7, no. 1, pp. 64–71, 2011.

[57] J. A. Carrino and R. Blanco, “Magnetic resonance-guidedmusculoskeletal interventional radiology,” Seminars in Muscu-loskeletal Radiology, vol. 10, no. 2, pp. 159–173, 2006.

[58] T. C. Dickey, R. Tych, M. Kliot, J. D. Loeser, K. Pederson, andP. D. Mourad, “Intense focused ultrasound can reliably inducesensations in human test subjects in a manner correlated withthe density of their mechanoreceptors,” Ultrasound in Medicine& Biology, vol. 38, no. 1, pp. 85–90, 2012.

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