{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T15:04:34Z","timestamp":1776351874952,"version":"3.51.2"},"reference-count":40,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Introduction\/Aims: Quantitative analysis of nerve echogenicity can support the diagnosis of mono- and polyneuropathies, for instance by distinguishing inflammatory-demyelinating from axonal damage. However, echogenicity is mainly assessed qualitatively and examiner-dependently. This study aimed to establish quantitative reference data for grayscale values of peripheral nerves in the upper and lower extremities of healthy children and adolescents to provide a clinical benchmark. Methods: We retrospectively analyzed ultrasound data from 211 healthy children aged two to seventeen years who had undergone standardized examinations of 15 peripheral nerve sites. Grayscale analysis (0\u2013255 levels per pixel) was performed within manually defined regions of interest (ROIs) using ImageJ (version 1.52). Echogenicity values were correlated with age, weight, height, and body mass index (BMI). Results: Echogenicity showed no significant overall association with biometric parameters. Mean grayscale values ranged from 85.23 \u00b1 2.16 for the tibial nerve at the medial malleolus to 134.62 \u00b1 2.69 for the sural nerve. Gain settings below 60 resulted in significantly lower grayscale values, whereas measurements with gain \u2265 60 were stable and comparable. Discussion: We propose reference grayscale ranges for peripheral nerves in healthy children and adolescents as a practical benchmark for clinical use and future studies. Due to technical constraints\u2014particularly retrospective image processing and non-lossless data export\u2014each laboratory should establish its own reference dataset, or multicentric parameters should be established. As our sample consisted predominantly of Caucasian participants, ethnic differences should be considered when applying these values to other populations.<\/jats:p>","DOI":"10.3390\/jcm15083051","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T14:05:36Z","timestamp":1776348336000},"page":"3051","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Quantitative Assessment of Peripheral Nerve Echogenicity in Children and Adolescents Aged 2\u201317 Years: A Retrospective Cross-Sectional Ultrasound Study"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5155-719X","authenticated-orcid":false,"given":"Jan-Hendrik","family":"Stahl","sequence":"first","affiliation":[{"name":"Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charlotte","family":"Schubert","sequence":"additional","affiliation":[{"name":"Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna-Sophie","family":"Grimm","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, University Children\u2019s Hospital T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5182-8295","authenticated-orcid":false,"given":"Lina Maria","family":"Serna-Higuita","sequence":"additional","affiliation":[{"name":"Department of Clinical Epidemiology and Applied Biostatistics, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cornelius","family":"Kronlage","sequence":"additional","affiliation":[{"name":"Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Wittlinger","sequence":"additional","affiliation":[{"name":"Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Magdalena","family":"Sch\u00fchle","sequence":"additional","affiliation":[{"name":"Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalie","family":"Winter","sequence":"additional","affiliation":[{"name":"Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Grimm","sequence":"additional","affiliation":[{"name":"Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3556","DOI":"10.1111\/ene.14959","article-title":"European Academy of Neurology\/Peripheral Nerve Society Guideline on Diagnosis and Treatment of Chronic Inflammatory Demyelinating Polyradiculoneuropathy: Report of a Joint Task Force\u2014Second Revision","volume":"28","author":"Doorn","year":"2021","journal-title":"Eur. J. Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1002\/mus.21619","article-title":"Repeatability of Ultrasonographic Median Nerve Measures","volume":"41","author":"Impink","year":"2010","journal-title":"Muscle Nerve"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1002\/mus.23417","article-title":"Reliability of Side-to-Side Ultrasound Cross-Sectional Area Measurements of Lower Extremity Nerves in Healthy Subjects","volume":"46","author":"Tagliafico","year":"2012","journal-title":"Muscle Nerve"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1002\/mus.25980","article-title":"Nerve Ultrasound Reliability of Upper Limbs: Effects of Examiner Training","volume":"57","author":"Dietz","year":"2018","journal-title":"Muscle Nerve"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1002\/mus.26029","article-title":"Nerve Ultrasound in Polyneuropathies","volume":"57","author":"Telleman","year":"2018","journal-title":"Muscle Nerve"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Onyeukwu, C., Saggar, R., Toncich, R.M., Dvorksy, J., and Fowler, J.R. (2025). Comparative Analysis of Methods for Obtaining Median Nerve Cross-Sectional Area Using Ultrasound. Hand, 15589447251366672.","DOI":"10.1177\/15589447251366672"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.clinph.2017.10.028","article-title":"Ultrasound and MRI of Nerves for Monitoring Disease Activity and Treatment Effects in Chronic Dysimmune Neuropathies\u2014Current Concepts and Future Directions","volume":"129","author":"Pham","year":"2018","journal-title":"Clin. Neurophysiol. Off. J. Int. Fed. Clin. Neurophysiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1002\/mus.24227","article-title":"Nerve Size in Chronic Inflammatory Demyelinating Neuropathy Varies with Disease Activity and Therapy Response over Time: A Retrospective Ultrasound Study","volume":"50","author":"Zaidman","year":"2014","journal-title":"Muscle Nerve"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1002\/mus.70091","article-title":"Nerve Ultrasound in Patients With Friedreich Ataxia","volume":"73","author":"Kneer","year":"2025","journal-title":"Muscle Nerve"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"fcad006","DOI":"10.1093\/braincomms\/fcad006","article-title":"Vagal Cross-Sectional Area Correlates with Parasympathetic Dysfunction in Parkinson\u2019s Disease","volume":"5","author":"Huckemann","year":"2023","journal-title":"Brain Commun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1002\/mus.24238","article-title":"Ultrasound Differentiation of Axonal and Demyelinating Neuropathies","volume":"50","author":"Grimm","year":"2014","journal-title":"Muscle Nerve"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e87","DOI":"10.1055\/a-2716-2279","article-title":"Traumatic Upper Extremity Nerve Lesions in Children: High-Resolution Nerve Ultrasound Can Improve Surgical Outcome","volume":"20","author":"Winter","year":"2025","journal-title":"J. Brachial Plex. Peripher. Nerve Inj."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1016\/j.clinph.2018.03.036","article-title":"Nerve Ultrasound Normal Values\u2014Readjustment of the Ultrasound Pattern Sum Score UPSS","volume":"129","author":"Grimm","year":"2018","journal-title":"Clin. Neurophysiol. Off. J. Int. Fed. Clin. Neurophysiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1016\/j.clinph.2013.03.007","article-title":"Cross Sectional Area Reference Values for Sonography of Peripheral Nerves and Brachial Plexus","volume":"124","author":"Kerasnoudis","year":"2013","journal-title":"Clin. Neurophysiol. Off. J. Int. Fed. Clin. Neurophysiol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Hsieh, P.-C., Chang, K.-H., Wu, Y.-R., Ro, L.-S., Chu, C.-C., Lyu, R.-K., Liao, M.-F., and Kuo, H.-C. (2021). Cross-Sectional Area Reference Values for Sonography of Peripheral Nerves in Taiwanese Adults. Front. Neurol., 12.","DOI":"10.3389\/fneur.2021.722403"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1590\/0100-3984.2022.0020","article-title":"Ultrasound Reference Values for Peripheral Nerve Cross-Sectional Areas and Indices in a Sample of Healthy Individuals in Brazil","volume":"55","author":"Voltan","year":"2022","journal-title":"Radiol. Bras."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1002\/mus.25617","article-title":"Ultrahigh-frequency Ultrasound of Fascicles in the Median Nerve at the Wrist","volume":"56","author":"Cartwright","year":"2017","journal-title":"Muscle Nerve"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3663","DOI":"10.1007\/s00415-022-10988-1","article-title":"Histopathology and High-Resolution Ultrasound Imaging for Peripheral Nerve (Injuries)","volume":"269","author":"Ricci","year":"2022","journal-title":"J. Neurol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"273","DOI":"10.21037\/qims.2019.02.05","article-title":"Shear Wave Elastography Evaluation of the Median and Tibial Nerve in Diabetic Peripheral Neuropathy","volume":"9","author":"He","year":"2019","journal-title":"Quant. Imaging Med. Surg."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Staber, D., Oppold, J., Grimm, A., Schuhmann, M.U., Romano, A., Marquetand, J., and Kleiser, B. (2022). Shear-Wave-Elastography in Neurofibromatosis Type I. Diagnostics, 12.","DOI":"10.3390\/diagnostics12020360"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1007\/s00415-018-9158-3","article-title":"Nerve Echogenicity and Intranerve CSA Variability in High-Resolution Nerve Ultrasound (HRUS) in Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)","volume":"266","author":"Fisse","year":"2019","journal-title":"J. Neurol."},{"key":"ref_22","first-page":"439","article-title":"Nerve Ultrasound Predicts Treatment Response in Chronic Inflammatory Demyelinating Polyradiculoneuropathy-a Prospective Follow-Up","volume":"15","author":"Ross","year":"2018","journal-title":"Neurother. J. Am. Soc. Exp. Neurother."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.clinph.2013.07.023","article-title":"Heterogeneity of Root and Nerve Ultrasound Pattern in CIDP Patients","volume":"125","author":"Padua","year":"2014","journal-title":"Clin. Neurophysiol. Off. J. Int. Fed. Clin. Neurophysiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1055\/a-0919-4768","article-title":"Nerve Ultrasonography as an Additive Tool to Clinical Examination and Electrodiagnostics in Sporadic Mononeuritis\u2014Imaging Is the Key","volume":"40","author":"Winter","year":"2019","journal-title":"Ultraschall Med.-Eur. J. Ultrasound"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Jain, S., Visser, L.H., Praveen, T.L.N., Rao, P.N., Surekha, T., Ellanti, R., Abhishek, T.L.N., and Nath, I. (2009). High-Resolution Sonography: A New Technique to Detect Nerve Damage in Leprosy. PLoS Neglected Trop. Dis., 3.","DOI":"10.1371\/journal.pntd.0000498"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1002\/mus.24981","article-title":"Facing the Diagnostic Challenge: Nerve Ultrasound in Diabetic Patients with Neuropathic Symptoms","volume":"54","author":"Pitarokoili","year":"2016","journal-title":"Muscle Nerve"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"199","DOI":"10.11152\/mu-1240","article-title":"Echogenicity and Ultrasound Visibility of Peripheral Nerves of the Upper Extremity","volume":"20","author":"Stolz","year":"2018","journal-title":"Med. Ultrason."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"797","DOI":"10.7863\/ultra.34.5.797","article-title":"Age-Related Differences in the Quantitative Echo Texture of the Median Nerve","volume":"34","author":"Li","year":"2015","journal-title":"J. Ultrasound Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1111\/jon.12717","article-title":"High-Resolution Nerve Ultrasound to Assess Nerve Echogenicity, Fascicular Count, and Cross-Sectional Area Using Semiautomated Analysis","volume":"30","author":"Gamber","year":"2020","journal-title":"J. Neuroimaging Off. J. Am. Soc. Neuroimaging"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1016\/j.clinph.2019.12.404","article-title":"Nerve Ultrasound Reference Data in Children from Two to Seven Years","volume":"131","author":"Schubert","year":"2020","journal-title":"Clin. Neurophysiol. Off. J. Int. Fed. Clin. Neurophysiol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Grimm, A.-S., Schubert, C., Grimm, A., Stahl, J.-H., K\u00fcpper, H., Horber, V., Kegele, J., Willikens, S., Wittlinger, J., and Serna-Higuita, L. (2020). Normative Observational Nerve Ultrasound Values in School-Age Children and Adolescents and Their Application to Hereditary Neuropathies. Front. Neurol., 11.","DOI":"10.3389\/fneur.2020.00303"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1097\/PHM.0000000000001134","article-title":"Artifacts and Artistic Facts: A Visual Simulation for Ultrasound Training","volume":"98","author":"Ricci","year":"2019","journal-title":"Am. J. Phys. Med. Rehabil."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1002\/mus.26151","article-title":"Muscle-ultrasound Evaluation in Healthy Pediatric Subjects: Age-related Normative Data","volume":"58","author":"Lori","year":"2018","journal-title":"Muscle Nerve"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1002\/mus.21866","article-title":"New Normal Values for Quantitative Muscle Ultrasound: Obesity Increases Muscle Echo Intensity","volume":"43","author":"Pillen","year":"2011","journal-title":"Muscle Nerve"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"VanHorn, T.A., and Cartwright, M.S. (2020). Neuromuscular Ultrasound in the Pediatric Population. Diagnostics, 10.","DOI":"10.3390\/diagnostics10121012"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1002\/mus.26499","article-title":"Nerve Conduction Normal Values for Electrodiagnosis in Pediatric Patients","volume":"60","author":"Ryan","year":"2019","journal-title":"Muscle Nerve"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1038\/s41598-024-84396-y","article-title":"Fascicle Differentiation of Upper Extremity Nerves on High-Resolution Ultrasound with Multimodal Microscopic Verification","volume":"15","author":"Saudek","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1016\/j.ultrasmedbio.2012.04.020","article-title":"Quantitative Ultrasound of Skeletal Muscle: Reliable Measurements of Calibrated Muscle Backscatter from Different Ultrasound Systems","volume":"38","author":"Zaidman","year":"2012","journal-title":"Ultrasound Med. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.ultrasmedbio.2022.08.007","article-title":"Repeatability, Reproducibility and Sources of Variability in the Assessment of Backscatter Coefficient and Texture Parameters from High-Frequency Ultrasound Acquisitions in Human Median Nerve","volume":"49","author":"Wu","year":"2023","journal-title":"Ultrasound Med. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1002\/mus.24124","article-title":"Difference in Normal Values of Median Nerve Cross-Sectional Area between Dutch and Indian Subjects","volume":"50","author":"Burg","year":"2014","journal-title":"Muscle Nerve"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/8\/3051\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T14:19:22Z","timestamp":1776349162000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/8\/3051"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,16]]},"references-count":40,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["jcm15083051"],"URL":"https:\/\/doi.org\/10.3390\/jcm15083051","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,16]]}}}