Abstract
Purpose
To determine normative morphological and functional magnetic resonance (MR) neurography values in children and adolescents in correlation to demographic determinants.
Methods
In this study 29 healthy underage subjects (mean age 13.9 years, range 10–17 years) were examined using a standardized MR neurography protocol of the lumbosacral plexus and the right lower extremity at 3 T. Volumes of the dorsal root ganglia L3–S2, cross-sectional area of the sciatic and tibial nerves, as well as T2-weighted contrast nerve-muscle ratio and quantitative diffusion tensor imaging (DTI) values of the sciatic nerve were obtained and correlated with the demographic parameters sex, age, height and weight.
Results
While all obtained morphological and functional MR neurography values did not differ between male and female sex, dorsal root ganglia volume, sciatic and tibial nerve cross-sectional area correlated positively with age, height, and weight. The T2-weighted signal of the sciatic nerve was independent of demographic determinants. Negative correlation was found for fractional anisotropy (FA) with age, height, and weight, whereas radial diffusivity (RD) showed a positive correlation only with age. Mean diffusivity (MD) and axial diffusivity (AD) revealed no correlation with demographic determinants.
Conclusion
The results of this study suggest that selection of sex-matched controls for further studies assessing peripheral nerve pathologies in underage patients may not be necessary; however, control subjects should be adapted to age, height, and weight of the patient population, especially if assessing dorsal root ganglia volume, nerve cross-sectional area and DTI.



References
Godel T, Bäumer P, Farschtschi S, Gugel I, Kronlage M, Hofstadler B, Heiland S, Gelderblom M, Bendszus M, Mautner VF. Peripheral nervous system alterations in infant and adult neurofibromatosis type 2. Neurology. 2019;93:e590–8.
Godel T, Bäumer P, Pham M, Köhn A, Muschol N, Kronlage M, Kollmer J, Heiland S, Bendszus M, Mautner VF. Human dorsal root ganglion in vivo morphometry and perfusion in Fabry painful neuropathy. Neurology. 2017;89:1274–82.
Godel T, Bäumer P, Stumpfe K, Muschol N, Kronlage M, Brunnée M, Kollmer J, Heiland S, Bendszus M, Mautner VF. Dorsal root ganglia volume is increased in patients with the Fabry-related GLA variant p.D313Y. J Neurol. 2019;266:1332-9.
Godel T, Köhn A, Muschol N, Kronlage M, Schwarz D, Kollmer J, Heiland S, Bendszus M, Mautner VF, Bäumer P. Dorsal root ganglia in vivo morphometry and perfusion in female patients with Fabry disease. J Neurol. 2018;265:2723-9.
Godel T, Mautner VF, Farschtschi S, Pham M, Schwarz D, Kronlage M, Gugel I, Heiland S, Bendszus M, Bäumer P. Dorsal root ganglia volume differentiates schwannomatosis and neurofibromatosis 2. Ann Neurol. 2018;83:854–7.
Kronlage M, Pitarokoili K, Schwarz D, Godel T, Heiland S, Yoon MS, Bendszus M, Bäumer P. Diffusion tensor imaging in chronic inflammatory demyelinating polyneuropathy: diagnostic accuracy and correlation with electrophysiology. Invest Radiol. 2017;52:701–7.
Pham M, Oikonomou D, Hornung B, Weiler M, Heiland S, Bäumer P, Kollmer J, Nawroth PP, Bendszus M. Magnetic resonance neurography detects diabetic neuropathy early and with proximal predominance. Ann Neurol. 2015;78:939–48.
Kollmer J, Hund E, Hornung B, Hegenbart U, Schönland SO, Kimmich C, Kristen AV, Purrucker J, Röcken C, Heiland S, Bendszus M, Pham M. In vivo detection of nerve injury in familial amyloid polyneuropathy by magnetic resonance neurography. Brain. 2015;138(Pt 3):549–62.
Bäumer P, Mautner VF, Bäumer T, Schuhmann MU, Tatagiba M, Heiland S, Kaestel T, Bendszus M, Pham M. Accumulation of non-compressive fascicular lesions underlies NF2 polyneuropathy. J Neurol. 2013;260:38–46.
Godel T, Pham M, Kele H, Kronlage M, Schwarz D, Brunée M, Heiland S, Bendszus M, Bäumer P. Diffusion tensor imaging in anterior interosseous nerve syndrome—functional MR Neurography on a fascicular level. Neuroimage Clin. 2019;21:101659.
Kronlage M, Schwehr V, Schwarz D, Godel T, Uhlmann L, Heiland S, Bendszus M, Bäumer P. Peripheral nerve diffusion tensor imaging (DTI): normal values and demographic determinants in a cohort of 60 healthy individuals. Eur Radiol. 2018;28:1801–8.
Naraghi AM, Awdeh H, Wadhwa V, Andreisek G, Chhabra A. Diffusion tensor imaging of peripheral nerves. Semin Musculoskelet Radiol. 2015;19:191–200.
Kallinikou D, Soldatou A, Tsentidis C, Louraki M, Kanaka-Gantenbein C, Kanavakis E, Karavanaki K. Diabetic neuropathy in children and adolescents with type 1 diabetes mellitus: diagnosis, pathogenesis, and associated genetic markers. Diabetes Metab Res Rev. 2019;13:e3178.
Kronlage M, Schwehr V, Schwarz D, Godel T, Heiland S, Bendszus M, Bäumer P. Magnetic resonance neurography : normal values and demographic determinants of nerve caliber and T2 relaxometry in 60 healthy individuals. Clin Neuroradiol. 2019;29:19–26.
Apostolidis L, Schwarz D, Xia A, Weiler M, Heckel A, Godel T, Heiland S, Schlemmer HP, Jäger D, Bendszus M, Bäumer P. Dorsal root ganglia hypertrophy as in vivo correlate of oxaliplatin-induced polyneuropathy. PLoS One. 2017;12:e183845.
Gadoth N, Sandbank U. Involvement of dorsal root ganglia in Fabry’s disease. J Med Genet. 1983;20:309–12.
Godel T, Pham M, Heiland S, Bendszus M, Bäumer P. Human dorsal-root-ganglion perfusion measured in-vivo by MRI. Neuroimage. 2016;141:81–7.
Kahn P. Anderson-Fabry disease: a histopathological study of three cases with observations on the mechanism of production of pain. J Neurol Neurosurg Psychiatry. 1973;36:1053–62.
Kaye EM, Kolodny EH, Logigian EL, Ullman MD. Nervous system involvement in Fabry’s disease: clinicopathological and biochemical correlation. Ann Neurol. 1988;23:505–9.
Gehlhausen JR, Park SJ, Hickox AE, Shew M, Staser K, Rhodes SD, Menon K, Lajiness JD, Mwanthi M, Yang X, Yuan J, Territo P, Hutchins G, Nalepa G, Yang FC, Conway SJ, Heinz MG, Stemmer-Rachamimov A, Yates CW, Wade Clapp D. A murine model of neurofibromatosis type 2 that accurately phenocopies human schwannoma formation. Hum Mol Genet. 2015;24:1–8.
Hasegawa T, Mikawa Y, Watanabe R, An HS. Morphometric analysis of the lumbosacral nerve roots and dorsal root ganglia by magnetic resonance imaging. Spine (Phila Pa 1976). 1996;21:1005-9.
West CA, McKay Hart A, Terenghi G, Wiberg M. Sensory neurons of the human brachial plexus: a quantitative study employing optical fractionation and in vivo volumetric magnetic resonance imaging. Neurosurgery. 2012;70:1183–94.
Cartwright MS, Passmore LV, Yoon JS, Brown ME, Caress JB, Walker FO. Cross-sectional area reference values for nerve ultrasonography. Muscle Nerve. 2008;37:566–71.
Cartwright MS, Shin HW, Passmore LV, Walker FO. Ultrasonographic findings of the normal ulnar nerve in adults. Arch Phys Med Rehabil. 2007;88:394–6.
Cartwright MS, Shin HW, Passmore LV, Walker FO. Ultrasonographic reference values for assessing the normal median nerve in adults. J Neuroimaging. 2009;19:47–51.
Kerasnoudis A, Pitarokoili K, Behrendt V, Gold R, Yoon MS. Cross sectional area reference values for sonography of peripheral nerves and brachial plexus. Clin Neurophysiol. 2013;124:1881–8.
Seok HY, Jang JH, Won SJ, Yoon JS, Park KS, Kim BJ. Cross-sectional area reference values of nerves in the lower extremities using ultrasonography. Muscle Nerve. 2014;50:564–70.
Won SJ, Kim BJ, Park KS, Yoon JS, Choi H. Reference values for nerve ultrasonography in the upper extremity. Muscle Nerve. 2013;47:864–71.
Cartwright MS, Mayans DR, Gillson NA, Griffin LP, Walker FO. Nerve cross-sectional area in extremes of age. Muscle Nerve. 2013;47:890–3.
Basser PJ, Mattiello J, LeBihan D. MR diffusion tensor spectroscopy and imaging. Biophys J. 1994;66:259–67.
Hagmann P, Jonasson L, Maeder P, Thiran JP, Wedeen VJ, Meuli R. Understanding diffusion MR imaging techniques: from scalar diffusion-weighted imaging to diffusion tensor imaging and beyond. Radiographics. 2006;26(Suppl 1):S205–23.
Guggenberger R, Markovic D, Eppenberger P, Chhabra A, Schiller A, Nanz D, Prüssmann K, Andreisek G.Assessment of median nerve with MR neurography by using diffusion-tensor imaging: normative and pathologic diffusion values. Radiology. 2012;265:194–203.
Breckwoldt MO, Stock C, Xia A, Heckel A, Bendszus M, Pham M, Heiland S, Bäumer P. Diffusion tensor imaging adds diagnostic accuracy in magnetic resonance neurography. Invest Radiol. 2015;50:498–504.
Hiltunen J, Suortti T, Arvela S, Seppä M, Joensuu R, Hari R. Diffusion tensor imaging and tractography of distal peripheral nerves at 3 T. Clin Neurophysiol. 2005;116:2315–23.
Hiltunen J, Kirveskari E, Numminen J, Lindfors N, Göransson H, Hari R. Pre- and post-operative diffusion tensor imaging of the median nerve in carpal tunnel syndrome. Eur Radiol. 2012;22:1310–9.
Bäumer P, Pham M, Ruetters M, Heiland S, Heckel A, Radbruch A, Bendszus M, Weiler M. Peripheral neuropathy: detection with diffusion-tensor imaging. Radiology. 2014;273:185–93.
Heckel A, Weiler M, Xia A, Ruetters M, Pham M, Bendszus M, Heiland S, Baeumer P. Peripheral nerve diffusion tensor imaging: assessment of axon and myelin sheath integrity. PLoS One. 2015;10:e0130833.
Budde MD, Kim JH, Liang HF, Schmidt RE, Russell JH, Cross AH, Song SK. Toward accurate diagnosis of white matter pathology using diffusion tensor imaging. Magn Reson Med. 2007;57:688–95.
DeBoy CA, Zhang J, Dike S, Shats I, Jones M, Reich DS, Mori S, Nguyen T, Rothstein B, Miller RH, Griffin JT, Kerr DA, Calabresi PA. High resolution diffusion tensor imaging of axonal damage in focal inflammatory and demyelinating lesions in rat spinal cord. Brain. 2007;130(Pt 8):2199–210.
Della Nave R, Ginestroni A, Diciotti S, Salvatore E, Soricelli A, Mascalchi M. Axial diffusivity is increased in the degenerating superior cerebellar peduncles of Friedreich’s ataxia. Neuroradiology. 2011;53:367–72.
Ugrenović S, Jovanović I, Vasović L, Kundalić B, Čukuranović R, Stefanović V. Morphometric analysis of the diameter and g‑ratio of the myelinated nerve fibers of the human sciatic nerve during the aging process. Anat Sci Int. 2016;91:238–45.
Acknowledgements
We thank all subjects for their valuable cooperation in this study. T.G. is supported by a postdoctoral fellowship from the Medical Faculty of the University of Heidelberg and received a research grant from Amicus Therapeutics. M.B. received grants from the German Research Council (SFB 1158). S.H. was supported by a grant from the German Research Council (SFB 1118).
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This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
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B. Hofstadler, P. Bäumer, D. Schwarz, M. Kronlage, S. Heiland, M. Bendszus and T. Godel declare that they have no competing interests.
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Hofstadler, B., Bäumer, P., Schwarz, D. et al. MR Neurography: Normative Values in Correlation to Demographic Determinants in Children and Adolescents. Clin Neuroradiol 30, 671–677 (2020). https://doi.org/10.1007/s00062-019-00834-9
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DOI: https://doi.org/10.1007/s00062-019-00834-9