Degenerative spinal cord compression is a frequent pathological condition with increasing prevalence throughout aging. Initial non-myelopathic cervical spinal cord compression (NMDC) might progress over time into potentially irreversible degenerative cervical myelopathy (DCM). While quantitative MRI (qMRI) techniques demonstrated the ability to depict intrinsic tissue properties, longitudinal in-vivo biomarkers to identify NMDC patients who will eventually develop DCM are still missing. Thus, we aim to review the ability of qMRI techniques (such as diffusion MRI, diffusion tensor imaging (DTI), magnetization transfer (MT) imaging, and magnetic resonance spectroscopy (1H-MRS)) to serve as prognostic markers in NMDC. While DTI in NMDC patients consistently detected lower fractional anisotropy and higher mean diffusivity at compressed levels, caused by demyelination and axonal injury, MT and 1H-MRS, along with advanced and tract-specific diffusion MRI, recently revealed microstructural alterations, also rostrally pointing to Wallerian degeneration. Recent studies also disclosed a significant relationship between microstructural damage and functional deficits, as assessed by qMRI and electrophysiology, respectively. Thus, tract-specific qMRI, in combination with electrophysiology, critically extends our understanding of the underlying pathophysiology of degenerative spinal cord compression and may provide predictive markers of DCM development for accurate patient management. However, the prognostic value must be validated in longitudinal studies.

Central European Institute of Technology Masaryk University 625 00 Brno Czech Republic

Danish Research Centre for Magnetic Resonance Centre for Functional and Diagnostic Imaging and Research Copenhagen University Hospital Amager and Hvidovre 2650 Hvidovre Denmark

Department of Biomedical Engineering University Hospital Olomouc 779 00 Olomouc Czech Republic

Department of Medicine 3 Clinical Division of Endocrinology and Metabolism Medical University of Vienna 1090 Vienna Austria

Department of Neurology Faculty of Medicine and Dentistry Palacký University Olomouc 779 00 Olomouc Czech Republic

Department of Neurology University Hospital Brno 625 00 Brno Czech Republic

Department of Neurology University Hospital Olomouc 779 00 Olomouc Czech Republic

Department of Radiology and Nuclear Medicine University Hospital Brno 625 00 Brno Czech Republic

Department of Radiology Centre for Functional and Diagnostic Imaging and Research Copenhagen University Hospital Amager and Hvidovre 2650 Hvidovre Denmark

Department of Radiology Faculty of Medicine and Dentistry Palacký University Olomouc 779 00 Olomouc Czech Republic

Faculty of Medicine Masaryk University 625 00 Brno Czech Republic

Zobrazit více v PubMed

Badhiwala J.H., Ahuja C.S., Akbar M.A., Witiw C.D., Nassiri F., Furlan J.C., Curt A., Wilson J.R., Fehlings M.G. Degenerative cervical myelopathy—Update and future directions. Nat. Rev. Neurol. 2020;16:108–124. doi: 10.1038/s41582-019-0303-0. PubMed DOI

Bednarik J., Kadanka Z., Dusek L., Novotny O., Surelova D., Urbanek I., Prokes B. Presymptomatic spondylotic cervical cord compression. Spine. 2004;29:2260–2269. doi: 10.1097/01.brs.0000142434.02579.84. PubMed DOI

Bednarik J., Kadanka Z., Dusek L., Kerkovsky M., Vohanka S., Novotny O., Urbanek I., Kratochvilova D. Presymptomatic spondylotic cervical myelopathy: An updated predictive model. Eur. Spine J. 2008;17:421–431. doi: 10.1007/s00586-008-0585-1. PubMed DOI PMC

Fehlings M.G., Tetreault L.A., Riew K.D., Middleton J.W., Aarabi B., Arnold P.M., Brodke D.S., Burns A.S., Carette S., Chen R., et al. A Clinical Practice Guideline for the Management of Patients with Degenerative Cervical Myelopathy: Recommendations for Patients with Mild, Moderate, and Severe Disease and Nonmyelopathic Patients with Evidence of Cord Compression. Glob. Spine J. 2017;7:70S–83S. doi: 10.1177/2192568217701914. PubMed DOI PMC

Valošek J., Labounek R., Horák T., Horáková M., Bednařík P., Keřkovský M., Kočica J., Rohan T., Lenglet C., Cohen-Adad J., et al. Diffusion magnetic resonance imaging reveals tract-specific microstructural correlates of electrophysiological impairments in non-myelopathic and myelopathic spinal cord compression. Eur. J. Neurol. 2021;28:3784–3797. doi: 10.1111/ene.15027. PubMed DOI PMC

Kovalova I., Kerkovsky M., Kadanka Z., Kadanka Z., Nemec M., Jurova B., Dusek L., Jarkovsky J., Bednarik J. Prevalence and imaging characteristics of nonmyelopathic and myelopathic spondylotic cervical cord compression. Spine. 2016;41:1908–1916. doi: 10.1097/BRS.0000000000001842. PubMed DOI

David G., Mohammadi S., Martin A.R., Cohen-Adad J., Weiskopf N., Thompson A., Freund P. Traumatic and nontraumatic spinal cord injury: Pathological insights from neuroimaging. Nat. Rev. Neurol. 2019;15:718–731. doi: 10.1038/s41582-019-0270-5. PubMed DOI

Kowalczyk I., Duggal N., Bartha R. Proton magnetic resonance spectroscopy of the motor cortex in cervical myelopathy. Brain. 2012;135:461–468. doi: 10.1093/brain/awr328. PubMed DOI

Bernabéu-Sanz Á., Mollá-Torró J.V., López-Celada S., Moreno López P., Fernández-Jover E. MRI evidence of brain atrophy, white matter damage, and functional adaptive changes in patients with cervical spondylosis and prolonged spinal cord compression. Eur. Radiol. 2020;30:357–369. doi: 10.1007/s00330-019-06352-z. PubMed DOI

Smith S.S., Stewart M.E., Davies B.M., Kotter M.R.N. The Prevalence of Asymptomatic and Symptomatic Spinal Cord Compression on Magnetic Resonance Imaging: A Systematic Review and Meta-analysis. Glob. Spine, J. 2021;11:597–607. doi: 10.1177/2192568220934496. PubMed DOI PMC

Witiw C.D., Mathieu F., Nouri A., Fehlings M.G. Clinico-Radiographic Discordance: An Evidence-Based Commentary on the Management of Degenerative Cervical Spinal Cord Compression in the Absence of Symptoms or With Only Mild Symptoms of Myelopathy. Glob. Spine J. 2018;8:527–534. doi: 10.1177/2192568217745519. PubMed DOI PMC

Wilson J.R., Barry S., Fischer D.J., Skelly A.C., Arnold P.M., Riew K.D., Shaffrey C.I., Traynelis V.C., Fehlings M.G. Frequency, Timing, and Predictors of Neurological Dysfunction in the Nonmyelopathic Patient with Cervical Spinal Cord Compression, Canal Stenosis, and/or Ossification of the Posterior Longitudinal Ligament. Spine. 2013;38:S37–S54. doi: 10.1097/BRS.0b013e3182a7f2e7. PubMed DOI

WFNS Cervical Spondylotic Myelopathy. [(accessed on 15 January 2022)]. Available online: http://wfns-spine.org/recom-cervical-spondylotic-myelopathy-1.

Oh T., Lafage R., Lafage V., Protopsaltis T., Challier V., Shaffrey C., Kim H.J., Arnold P., Chapman J., Schwab F., et al. Comparing Quality of Life in Cervical Spondylotic Myelopathy with Other Chronic Debilitating Diseases Using the Short Form Survey 36-Health Survey. World Neurosurg. 2017;106:699–706. doi: 10.1016/j.wneu.2016.12.124. PubMed DOI

Baptiste D.C., Fehlings M.G. Pathophysiology of cervical myelopathy. Spine J. 2006;6:190–197. doi: 10.1016/j.spinee.2006.04.024. PubMed DOI

Akter F., Yu X., Qin X., Yao S., Nikrouz P., Syed Y.A., Kotter M. The Pathophysiology of Degenerative Cervical Myelopathy and the Physiology of Recovery Following Decompression. Front. Neurosci. 2020;14:138. doi: 10.3389/fnins.2020.00138. PubMed DOI PMC

Akter F., Kotter M. Pathobiology of Degenerative Cervical Myelopathy. Neurosurg. Clin. N. Am. 2018;29:13–19. doi: 10.1016/j.nec.2017.09.015. PubMed DOI

Tu J., Vargas Castillo J., Das A., Diwan A.D. Degenerative Cervical Myelopathy: Insights into Its Pathobiology and Molecular Mechanisms. J. Clin. Med. 2021;10:1214. doi: 10.3390/jcm10061214. PubMed DOI PMC

Guan X., Fan G., Wu X., Gu G., Gu X., Zhang H., He S. Diffusion Tensor Imaging Studies of Cervical Spondylotic Myelopathy: A Systemic Review and Meta-Analysis. PLoS ONE. 2015;10:e0117707. doi: 10.1371/journal.pone.0117707. PubMed DOI PMC

Ellingson B.M., Salamon N., Holly L.T. Advances in MR imaging for cervical spondylotic myelopathy. Eur. Spine J. 2015;24:197–208. doi: 10.1007/s00586-013-2915-1. PubMed DOI PMC

Kerkovský M., Bednarík J., Dušek L., Šprláková-Puková A., Urbánek I., Mechl M., Válek V., Kadanka Z. Magnetic Resonance Diffusion Tensor Imaging in Patients with Cervical Spondylotic Spinal Cord Compression. Spine. 2012;37:48–56. doi: 10.1097/BRS.0b013e31820e6c35. PubMed DOI

Adamova B., Bednarik J., Andrasinova T., Kovalova I., Kopacik R., Jabornik M., Kerkovsky M., Jakubcova B., Jarkovsky J. Does lumbar spinal stenosis increase the risk of spondylotic cervical spinal cord compression? Eur. Spine J. 2015;24:2946–2953. doi: 10.1007/s00586-015-4049-0. PubMed DOI

Keřkovský M., Bednařík J., Jurová B., Dušek L., Kadaňka Z., Kadaňka Z., Němec M., Kovaľová I., Šprláková-Puková A., Mechl M. Spinal Cord MR Diffusion Properties in Patients with Degenerative Cervical Cord Compression. J. Neuroimaging. 2017;27:149–157. doi: 10.1111/jon.12372. PubMed DOI

Ellingson B.M., Salamon N., Woodworth D.C., Yokota H., Holly L.T. Reproducibility, temporal stability, and functional correlation of diffusion MR measurements within the spinal cord in patients with asymptomatic cervical stenosis or cervical myelopathy. J. Neurosurg. Spine. 2018;28:472–480. doi: 10.3171/2017.7.SPINE176. PubMed DOI PMC

Martin A.R., De Leener B., Cohen-Adad J., Cadotte D.W., Nouri A., Wilson J.R., Tetreault L., Crawley A.P., Mikulis D.J., Ginsberg H., et al. Can microstructural MRI detect subclinical tissue injury in subjects with asymptomatic cervical spinal cord compression? A prospective cohort study. BMJ Open. 2018;8:e019809. doi: 10.1136/bmjopen-2017-019809. PubMed DOI PMC

Kadanka Z., Adamova B., Kerkovsky M., Kadanka Z., Dusek L., Jurova B., Vlckova E., Bednarik J. Predictors of symptomatic myelopathy in degenerative cervical spinal cord compression. Brain Behav. 2017;7:e00797. doi: 10.1002/brb3.797. PubMed DOI PMC

Labounek R., Valošek J., Horák T., Svátková A., Bednařík P., Vojtíšek L., Horáková M., Nestrašil I., Lenglet C., Cohen-Adad J., et al. HARDI-ZOOMit protocol improves specificity to microstructural changes in presymptomatic myelopathy. Sci. Rep. 2020;10:17529. doi: 10.1038/s41598-020-70297-3. PubMed DOI PMC

Kadanka Z., Kadanka Z., Skutil T., Vlckova E., Bednarik J. Walk and Run Test in Patients with Degenerative Compression of the Cervical Spinal Cord. J. Clin. Med. 2021;10:927. doi: 10.3390/jcm10050927. PubMed DOI PMC

Horak T., Horakova M., Svatkova A., Kadanka Z., Kudlicka P., Valosek J., Rohan T., Kerkovsky M., Vlckova E., Kadanka Z., et al. In vivo Molecular Signatures of Cervical Spinal Cord Pathology in Degenerative Compression. J. Neurotrauma. 2021;38:2999–3010. doi: 10.1089/neu.2021.0151. PubMed DOI PMC

Horáková M., Horák T., Valošek J., Rohan T., Koriťáková E., Dostál M., Kočica J., Skutil T., Keřkovský M., Kadaňka Z., Jr., et al. Semi-automated detection of cervical spinal cord compression with the Spinal Cord Toolbox. Quant. Imaging Med. Surg. 2022;12:2261–2279. doi: 10.21037/qims-21-782. PubMed DOI PMC

Nouri A., Martin A.R., Kato S., Reihani-Kermani H., Riehm L.E., Fehlings M.G. The Relationship between MRI Signal Intensity Changes, Clinical Presentation, and Surgical Outcome in Degenerative Cervical Myelopathy. Spine. 2017;42:1851–1858. doi: 10.1097/BRS.0000000000002234. PubMed DOI

Martin A.R., Tetreault L., Nouri A., Curt A., Freund P., Rahimi-Movaghar V., Wilson J.R., Fehlings M.G., Kwon B.K., Harrop J.S., et al. Imaging and Electrophysiology for Degenerative Cervical Myelopathy [AO Spine RECODE-DCM Research Priority Number 9] Glob. Spine J. 2022;12:130S–146S. doi: 10.1177/21925682211057484. PubMed DOI PMC

Nouri A., Martin A.R., Mikulis D., Fehlings M.G. Magnetic resonance imaging assessment of degenerative cervical myelopathy: A review of structural changes and measurement techniques. Neurosurg. Focus. 2016;40:E5. doi: 10.3171/2016.3.FOCUS1667. PubMed DOI

Kato F., Yukawa Y., Suda K., Yamagata M., Ueta T. Normal morphology, age-related changes and abnormal findings of the cervical spine. Part II: Magnetic resonance imaging of over 1200 asymptomatic subjects. Eur. Spine J. 2012;21:1499–1507. doi: 10.1007/s00586-012-2176-4. PubMed DOI PMC

Martin A.R., De Leener B., Cohen-Adad J., Kalsi-Ryan S., Cadotte D.W., Wilson J.R., Tetreault L., Nouri A., Crawley A., Mikulis D.J., et al. Monitoring for myelopathic progression with multiparametric quantitative MRI. PLoS ONE. 2018;13:e0195733. doi: 10.1371/journal.pone.0195733. PubMed DOI PMC

Grabher P., Mohammadi S., David G., Freund P. Neurodegeneration in the Spinal Ventral Horn Prior to Motor Impairment in Cervical Spondylotic Myelopathy. J. Neurotrauma. 2017;34:2329–2334. doi: 10.1089/neu.2017.4980. PubMed DOI

Grabher P., Mohammadi S., Trachsler A., Friedl S., David G., Sutter R., Weiskopf N., Thompson A.J., Curt A., Freund P. Voxel-based analysis of grey and white matter degeneration in cervical spondylotic myelopathy. Sci. Rep. 2016;6:24636. doi: 10.1038/srep24636. PubMed DOI PMC

Valošek J., Bednařík P., Horák T., Horáková M., Svátková A., Labounek R., Hluštík P., Bednařík J. Cervical Spinal Cord Atrophy Above Level of Asymptomatic Degenerative Cervical Cord Compression; Proceedings of the 26th Annual Meeting of the Organization for Human Brain Mapping; Virtual. 23 June–3 July 2020; p. 3136.

Vallotton K., David G., Hupp M., Pfender N., Cohen-Adad J., Fehlings M.G., Samson R.S., Wheeler-Kingshott C.A.M.G., Curt A., Freund P., et al. Tracking White and Gray Matter Degeneration along the Spinal Cord Axis in Degenerative Cervical Myelopathy. J. Neurotrauma. 2021;38:2978–2987. doi: 10.1089/neu.2021.0148. PubMed DOI

David G., Vallotton K., Hupp M., Curt A., Freund P., Seif M. Extent of Cord Pathology in the Lumbosacral Enlargement in Non-Traumatic versus Traumatic Spinal Cord Injury. J. Neurotrauma. 2022 doi: 10.1089/neu.2021.0389. PubMed DOI

Lévy S., Benhamou M., Naaman C., Rainville P., Callot V., Cohen-Adad J. White matter atlas of the human spinal cord with estimation of partial volume effect. Neuroimage. 2015;119:262–271. doi: 10.1016/j.neuroimage.2015.06.040. PubMed DOI

Johansen-Berg H., Behrens T.E.J. Diffusion MRI: From Quantitative Measurement to In Vivo Neuroanatomy. 2nd ed. Elsevier Science; Amsterdam, The Netherlands: 2013.

Martin A.R., Aleksanderek I., Cohen-Adad J., Tarmohamed Z., Tetreault L., Smith N., Cadotte D.W., Crawley A., Ginsberg H., Mikulis D.J., et al. Translating state-of-the-art spinal cord MRI techniques to clinical use: A systematic review of clinical studies utilizing DTI, MT, MWF, MRS, and fMRI. NeuroImage Clin. 2016;10:192–238. doi: 10.1016/j.nicl.2015.11.019. PubMed DOI PMC

Mori S., Tournier J.-D. Introduction to Diffusion Tensor Imaging: And Higher Order Models. 2nd ed. Academic Press; Amsterdam, The Netherlands: 2014.

Cohen-Adad J. Microstructural imaging in the spinal cord and validation strategies. Neuroimage. 2018;182:169–183. doi: 10.1016/j.neuroimage.2018.04.009. PubMed DOI

Hori M., Hagiwara A., Fukunaga I., Ueda R., Kamiya K., Suzuki Y., Liu W., Murata K., Takamura T., Hamasaki N., et al. Application of Quantitative Microstructural MR Imaging with Atlas-based Analysis for the Spinal Cord in Cervical Spondylotic Myelopathy. Sci. Rep. 2018;8:5213. doi: 10.1038/s41598-018-23527-8. PubMed DOI PMC

Iwama T., Ohba T., Okita G., Ebata S., Ueda R., Motosugi U., Onishi H., Haro H., Hori M. Utility and validity of neurite orientation dispersion and density imaging with diffusion tensor imaging to quantify the severity of cervical spondylotic myelopathy and assess postoperative neurological recovery. Spine J. 2020;20:417–425. doi: 10.1016/j.spinee.2019.10.019. PubMed DOI

Grussu F., Schneider T., Zhang H., Alexander D.C., Wheeler-Kingshott C.A.M. Single-shell diffusion MRI NODDI with in vivo cervical cord data; Proceedings of the ISMRM; Milan, Italy. 10–16 May 2014;

Grussu F., Schneider T., Zhang H., Alexander D.C., Wheeler-Kingshott C.A.M. Neurite orientation dispersion and density imaging of the healthy cervical spinal cord in vivo. Neuroimage. 2015;111:590–601. doi: 10.1016/j.neuroimage.2015.01.045. PubMed DOI

Grussu F., Schneider T., Tur C., Yates R.L., Tachrount M., Ianus ß A., Yiannakas M.C., Newcombe J., Zhang H., Alexander D.C., et al. Neurite dispersion: A new marker of multiple sclerosis spinal cord pathology? Ann. Clin. Transl. Neurol. 2017;4:663–679. doi: 10.1002/acn3.445. PubMed DOI PMC

Okita G., Ohba T., Takamura T., Ebata S., Ueda R., Onishi H., Haro H., Hori M. Application of neurite orientation dispersion and density imaging or diffusion tensor imaging to quantify the severity of cervical spondylotic myelopathy and to assess postoperative neurologic recovery. Spine J. 2018;18:268–275. doi: 10.1016/j.spinee.2017.07.007. PubMed DOI

Hori M., Tsutsumi S., Yasumoto Y., Ito M., Suzuki M., Tanaka F.S., Kyogoku S., Nakamura M., Tabuchi T., Fukunaga I., et al. Cervical spondylosis: Evaluation of microstructural changes in spinal cord white matter and gray matter by diffusional kurtosis imaging. Magn. Reson. Imaging. 2014;32:428–432. doi: 10.1016/j.mri.2014.01.018. PubMed DOI

Hori M., Fukunaga I., Masutani Y., Nakanishi A., Shimoji K., Kamagata K., Asahi K., Hamasaki N., Suzuki Y., Aoki S. New diffusion metrics for spondylotic myelopathy at an early clinical stage. Eur. Radiol. 2012;22:1797–1802. doi: 10.1007/s00330-012-2410-9. PubMed DOI PMC

Lee J.W., Kim J.H., Park J.B., Park K.W., Yeom J.S., Lee G.Y., Kang H.S. Diffusion tensor imaging and fiber tractography in cervical compressive myelopathy: Preliminary results. Skeletal Radiol. 2011;40:1543–1551. doi: 10.1007/s00256-011-1161-z. PubMed DOI

Ellingson B.M., Salamon N., Grinstead J.W., Holly L.T. Diffusion tensor imaging predicts functional impairment in mild-to-moderate cervical spondylotic myelopathy. Spine J. 2014;14:2589–2597. doi: 10.1016/j.spinee.2014.02.027. PubMed DOI PMC

Wen C.Y., Cui J.L., Liu H.S., Mak K.C., Cheung W.Y., Luk K.D.K., Hu Y. Is diffusion anisotropy a biomarker for disease severity and surgical prognosis of cervical spondylotic myelopathy. Radiology. 2014;270:197–204. doi: 10.1148/radiol.13121885. PubMed DOI

Jones J.G.A., Cen S.Y., Lebel R.M., Hsieh P.C., Law M. Diffusion tensor imaging correlates with the clinical assessment of disease severity in cervical spondylotic myelopathy and predicts outcome following surgery. Am. J. Neuroradiol. 2013;34:471–478. doi: 10.3174/ajnr.A3199. PubMed DOI PMC

Uda T., Takami T., Tsuyuguchi N., Sakamoto S., Yamagata T., Ikeda H., Nagata T., Ohata K. Assessment of cervical spondylotic myelopathy using diffusion tensor magnetic resonance imaging parameter at 3.0 tesla. Spine. 2013;38:407–414. doi: 10.1097/BRS.0b013e31826f25a3. PubMed DOI

Banaszek A., Bladowska J., Szewczyk P., Podgórski P., Sąsiadek M. Usefulness of diffusion tensor MR imaging in the assessment of intramedullary changes of the cervical spinal cord in different stages of degenerative spine disease. Eur. Spine J. 2014;23:1523–1530. doi: 10.1007/s00586-014-3323-x. PubMed DOI

Wen C.Y., Cui J.L., Mak K.C., Luk K.D.K., Hu Y. Diffusion tensor imaging of somatosensory tract in cervical spondylotic myelopathy and its link with electrophysiological evaluation. Spine J. 2014;14:1493–1500. doi: 10.1016/j.spinee.2013.08.052. PubMed DOI

Maki S., Koda M., Ota M., Oikawa Y., Kamiya K., Inada T., Furuya T., Takahashi K., Masuda Y., Matsumoto K., et al. Reduced Field-of-View Diffusion Tensor Imaging of the Spinal Cord Shows Motor Dysfunction of the Lower Extremities in Patients with Cervical Compression Myelopathy. Spine. 2018;43:89–96. doi: 10.1097/BRS.0000000000001123. PubMed DOI

Maki S., Koda M., Saito J., Takahashi S., Inada T., Kamiya K., Ota M., Iijima Y., Masuda Y., Matsumoto K., et al. Tract-Specific Diffusion Tensor Imaging Reveals Laterality of Neurological Symptoms in Patients with Cervical Compression Myelopathy. World Neurosurg. 2016;96:184–190. doi: 10.1016/j.wneu.2016.08.129. PubMed DOI

Cui J.L., Li X., Chan T.Y., Mak K.C., Luk K.D.K., Hu Y. Quantitative assessment of column-specific degeneration in cervical spondylotic myelopathy based on diffusion tensor tractography. Eur. Spine J. 2015;24:41–47. doi: 10.1007/s00586-014-3522-5. PubMed DOI

Budzik J.F., Balbi V., Le Thuc V., Duhamel A., Assaker R., Cotten A. Diffusion tensor imaging and fibre tracking in cervical spondylotic myelopathy. Eur. Radiol. 2011;21:426–433. doi: 10.1007/s00330-010-1927-z. PubMed DOI

Seif M., David G., Huber E., Vallotton K., Curt A., Freund P. Cervical Cord Neurodegeneration in Traumatic and Non-Traumatic Spinal Cord Injury. J. Neurotrauma. 2020;37:860–867. doi: 10.1089/neu.2019.6694. PubMed DOI PMC

Wang K.Y., Idowu O., Thompson C.B., Orman G., Myers C., Riley L.H., Carrino J.A., Flammang A., Gilson W., Sadowsky C.L., et al. Tract-Specific Diffusion Tensor Imaging in Cervical Spondylotic Myelopathy Before and After Decompressive Spinal Surgery: Preliminary Results. Clin. Neuroradiol. 2017;27:61–69. doi: 10.1007/s00062-015-0418-7. PubMed DOI

Rajasekaran S., Yerramshetty J.S., Chittode V.S., Kanna R.M., Balamurali G., Shetty A.P. The Assessment of Neuronal Status in Normal and Cervical Spondylotic Myelopathy Using Diffusion Tensor Imaging. Spine. 2014;39:1183–1189. doi: 10.1097/BRS.0000000000000369. PubMed DOI

Zhang M., Ou-Yang H., Liu J., Jin D., Wang C., Zhang X., Zhao Q., Liu X., Liu Z., Lang N., et al. Utility of Advanced DWI in the Detection of Spinal Cord Microstructural Alterations and Assessment of Neurologic Function in Cervical Spondylotic Myelopathy Patients. J. Magn. Reson. Imaging. 2022;55:930–940. doi: 10.1002/jmri.27894. PubMed DOI

Mamata H., Jolesz F.A., Maier S.E. Apparent diffusion coefficient and fractional anisotropy in spinal cord: Age and cervical spondylosis-related changes. J. Magn. Reson. Imaging. 2005;22:38–43. doi: 10.1002/jmri.20357. PubMed DOI

Rao A., Soliman H., Kaushal M., Motovylyak O., Vedantam A., Budde M.D., Schmit B., Wang M., Kurpad S.N. Diffusion Tensor Imaging in a Large Longitudinal Series of Patients with Cervical Spondylotic Myelopathy Correlated with Long-Term Functional Outcome. Neurosurgery. 2018;83:753–760. doi: 10.1093/neuros/nyx558. PubMed DOI

Mair W.G.P., Druckman R. The pathology of spinal cord lesions and their relation to the clinical features in protrusion of cervical intervertebral discs (a report of four cases) Brain. 1953;76:70–91. doi: 10.1093/brain/76.1.70. PubMed DOI

Lindberg P.G., Sanchez K., Ozcan F., Rannou F., Poiraudeau S., Feydy A., Maier M.A. Correlation of force control with regional spinal DTI in patients with cervical spondylosis without signs of spinal cord injury on conventional MRI. Eur. Radiol. 2016;26:733–742. doi: 10.1007/s00330-015-3876-z. PubMed DOI

Behrens T.E.J., Woolrich M.W., Jenkinson M., Johansen-Berg H., Nunes R.G., Clare S., Matthews P.M., Brady J.M., Smith S.M. Characterization and Propagation of Uncertainty in Diffusion-Weighted MR Imaging. Magn. Reson. Med. 2003;50:1077–1088. doi: 10.1002/mrm.10609. PubMed DOI

Panagiotaki E., Schneider T., Siow B., Hall M.G., Lythgoe M.F., Alexander D.C. Compartment models of the diffusion MR signal in brain white matter: A taxonomy and comparison. Neuroimage. 2012;59:2241–2254. doi: 10.1016/j.neuroimage.2011.09.081. PubMed DOI

Zhang H., Schneider T., Wheeler-Kingshott C.A., Alexander D.C. NODDI: Practical in vivo neurite orientation dispersion and density imaging of the human brain. Neuroimage. 2012;61:1000–1016. doi: 10.1016/j.neuroimage.2012.03.072. PubMed DOI

Le Bihan D. What can we see with IVIM MRI? Neuroimage. 2019;187:56–67. doi: 10.1016/j.neuroimage.2017.12.062. PubMed DOI

Lévy S., Rapacchi S., Massire A., Troalen T., Feiweier T., Guye M., Callot V. Intravoxel Incoherent Motion at 7 Tesla to quantify human spinal cord perfusion: Limitations and promises. Magn. Reson. Med. 2020;84:1198–1217. doi: 10.1002/mrm.28195. PubMed DOI

Lévy S., Freund P., Callot V., Seif M. Spinal cord perfusion mapping using Intra-Voxel Incoherent Motion at 3T in healthy individuals and Degenerative Cervical Myelopathy patients; Proceedings of the 29th Annual Meeting ISMRM; Virtual. 15–20 May 2021; p. 3462.

Cohen-Adad J., Wheeler-Kingshott C. Quantitative MRI of the Spinal Cord. Elsevier; Amsterdam, The Netherlands: 2014.

Schmierer K., Scaravilli F., Altmann D.R., Barker G.J., Miller D.H. Magnetization transfer ratio and myelin in postmortem multiple sclerosis brain. Ann. Neurol. 2004;56:407–415. doi: 10.1002/ana.20202. PubMed DOI

Paliwal M., Weber K.A., Hopkins B.S., Cantrell D.R., Hoggarth M.A., Elliott J.M., Dahdaleh N.S., Mackey S., Parrish T.D., Dhaher Y., et al. Magnetization Transfer Ratio and Morphometrics of the Spinal Cord Associates with Surgical Recovery in Patients with Degenerative Cervical Myelopathy. World Neurosurg. 2020;144:e939–e947. doi: 10.1016/j.wneu.2020.09.148. PubMed DOI PMC

Öz G., Alger J.R., Barker P.B., Bartha R., Bizzi A., Boesch C., Bolan P.J., Brindle K.M., Cudalbu C., Dinçer A., et al. Clinical Proton MR Spectroscopy in Central Nervous System Disorders. Radiology. 2014;270:658–679. doi: 10.1148/radiol.13130531. PubMed DOI PMC

Öz G. Contemporary Clinical Neuroscience. Springer; Cham, Switzerland: 2016. Imaging Neurodegeneration: What Can Magnetic Resonance Spectroscopy Contribute? pp. 1–11.

Aleksanderek I., McGregor S.M.K., Stevens T.K., Goncalves S., Bartha R., Duggal N. Cervical spondylotic myelopathy: Metabolite changes in the primary motor cortex after surgery. Radiology. 2017;282:817–825. doi: 10.1148/radiol.2016152083. PubMed DOI

Holly L.T., Ellingson B.M., Salamon N. Metabolic imaging using proton magnetic spectroscopy as a predictor of outcome after surgery for cervical spondylotic myelopathy. Clin. Spine Surg. 2017;30:E615–E619. doi: 10.1097/BSD.0000000000000248. PubMed DOI PMC

Ellingson B.M., Salamon N., Hardy A.J., Holly L.T. Prediction of neurological impairment in cervical spondylotic myelopathy using a combination of diffusion mri and proton mr spectroscopy. PLoS ONE. 2015;10:e0139451. doi: 10.1371/journal.pone.0139451. PubMed DOI PMC

Aleksanderek I., Stevens T.K., Goncalves S., Bartha R., Duggal N. Metabolite and functional profile of patients with cervical spondylotic myelopathy. J. Neurosurg. Spine. 2017;26:547–553. doi: 10.3171/2016.9.SPINE151507. PubMed DOI

Salamon N., Ellingson B.M., Nagarajan R., Gebara N., Thomas A., Holly L.T. Proton magnetic resonance spectroscopy of human cervical spondylosis at 3T. Spinal Cord. 2013;51:558–563. doi: 10.1038/sc.2013.31. PubMed DOI PMC

Wilson M., Andronesi O., Barker P.B., Bartha R., Bizzi A., Bolan P.J., Brindle K.M., Choi I., Cudalbu C., Dydak U., et al. Methodological consensus on clinical proton MRS of the brain: Review and recommendations. Magn. Reson. Med. 2019;82:527–550. doi: 10.1002/mrm.27742. PubMed DOI PMC

Wyss P.O., Huber E., Curt A., Kollias S., Freund P., Henning A. MR spectroscopy of the cervical spinal cord in chronic spinal cord injury. Radiology. 2019;291:131–138. doi: 10.1148/radiol.2018181037. PubMed DOI

Maier I.L., Hofer S., Eggert E., Schregel K., Psychogios M.-N., Frahm J., Bähr M., Liman J. T1 Mapping Quantifies Spinal Cord Compression in Patients with Various Degrees of Cervical Spinal Canal Stenosis. Front. Neurol. 2020;11:1427. doi: 10.3389/fneur.2020.574604. PubMed DOI PMC

Baucher G., Rasoanandrianina H., Levy S., Pini L., Troude L., Roche P.-H., Callot V. T1 Mapping for Microstructural Assessment of the Cervical Spinal Cord in the Evaluation of Patients with Degenerative Cervical Myelopathy. Am. J. Neuroradiol. 2021;42:1348–1357. doi: 10.3174/ajnr.A7157. PubMed DOI PMC

Liu H., MacMillian E.L., Jutzeler C.R., Ljungberg E., MacKay A.L., Kolind S.H., Mädler B., Li D.K.B., Dvorak M.F., Curt A., et al. Assessing structure and function of myelin in cervical spondylotic myelopathy. Neurology. 2017;89:602–610. doi: 10.1212/WNL.0000000000004197. PubMed DOI PMC

Dvorak A.V., Ljungberg E., Vavasour I.M., Lee L.E., Abel S., Li D.K.B., Traboulsee A., MacKay A.L., Kolind S.H. Comparison of multi echo T2 relaxation and steady state approaches for myelin imaging in the central nervous system. Sci. Rep. 2021;11:1369. doi: 10.1038/s41598-020-80585-7. PubMed DOI PMC

Glover G.H. Overview of Functional Magnetic Resonance Imaging. Neurosurg. Clin. N. Am. 2011;22:133–139. doi: 10.1016/j.nec.2010.11.001. PubMed DOI PMC

Duggal N., Rabin D., Bartha R., Barry R.L., Gati J.S., Kowalczyk I., Fink M. Brain reorganization in patients with spinal cord compression evaluated using fMRI. Neurology. 2010;74:1048–1054. doi: 10.1212/WNL.0b013e3181d6b0ea. PubMed DOI

Tan Y., Zhou F., Wu L., Liu Z., Zeng X., Gong H., He L. Alteration of Regional Homogeneity within the Sensorimotor Network after Spinal Cord Decompression in Cervical Spondylotic Myelopathy: A Resting-State fMRI Study. Biomed Res. Int. 2015;2015:1–6. doi: 10.1155/2015/647958. PubMed DOI PMC

Cronin A.E., Detombe S.A., Duggal C.A., Duggal N., Bartha R. Spinal cord compression is associated with brain plasticity in degenerative cervical myelopathy. Brain Commun. 2021;3:fcab131. doi: 10.1093/braincomms/fcab131. PubMed DOI PMC

Hrabálek L., Hok P., Hluštík P., Čecháková E., Wanek T., Otruba P., Vaverka M., Kaňovský P. Longitudinal brain activation changes related to electrophysiological findings in patients with cervical spondylotic myelopathy before and after spinal cord decompression: An fMRI study. Acta Neurochir. 2018;160:923–932. doi: 10.1007/s00701-018-3520-1. PubMed DOI

Liu X., Qian W., Jin R., Li X., Luk K.D., Wu E.X., Hu Y. Amplitude of Low Frequency Fluctuation (ALFF) in the Cervical Spinal Cord with Stenosis: A Resting State fMRI Study. PLoS ONE. 2016;11:e0167279. doi: 10.1371/journal.pone.0167279. PubMed DOI PMC

Powers J., Ioachim G., Stroman P. Ten Key Insights into the Use of Spinal Cord fMRI. Brain Sci. 2018;8:173. doi: 10.3390/brainsci8090173. PubMed DOI PMC

Eippert F., Kong Y., Jenkinson M., Tracey I., Brooks J.C.W. Denoising spinal cord fMRI data: Approaches to acquisition and analysis. Neuroimage. 2017;154:255–266. doi: 10.1016/j.neuroimage.2016.09.065. PubMed DOI

Ellingson B.M., Woodworth D.C., Leu K., Salamon N., Holly L.T. Spinal Cord Perfusion MR Imaging Implicates Both Ischemia and Hypoxia in the Pathogenesis of Cervical Spondylosis. World Neurosurg. 2019;128:e773–e781. doi: 10.1016/j.wneu.2019.04.253. PubMed DOI PMC

Uemura K., Matsumura A., Isobe T., Anno I., Kawamura H., Minami M., Tsukada A. Perfusion-Weighted Magnetic Resonance Imaging of the Spinal Cord in Cervical Spondylotic Myelopathy. Neurol. Med. Chir. 2006;46:581–588. doi: 10.2176/nmc.46.581. PubMed DOI

Zhou F., Huang M., Wu L., Tan Y., Guo J., Zhang Y., He L., Gong H. Altered perfusion of the sensorimotor cortex in patients with cervical spondylotic myelopathy: An arterial spin labeling study. J. Pain Res. 2018;11:181–190. doi: 10.2147/JPR.S148076. PubMed DOI PMC

Sherman J.L., Nassaux P.Y., Citrin C.M. Measurements of the normal cervical spinal cord on MR imaging. Am. J. Neuroradiol. 1990;11:369–372. PubMed PMC

Cohen-Adad J., Alonso-Ortiz E., Abramovic M., Arneitz C., Atcheson N., Barlow L., Barry R.L., Barth M., Battiston M., Büchel C., et al. Generic acquisition protocol for quantitative MRI of the spinal cord. Nat. Protoc. 2021;16:4611–4632. doi: 10.1038/s41596-021-00588-0. PubMed DOI PMC

Cohen-Adad J., Alonso-Ortiz E., Abramovic M., Arneitz C., Atcheson N., Barlow L., Barry R.L., Barth M., Battiston M., Büchel C., et al. Open-access quantitative MRI data of the spinal cord and reproducibility across participants, sites and manufacturers. Sci. Data. 2021;8:219. doi: 10.1038/s41597-021-00941-8. PubMed DOI PMC

Samson R.S., Lévy S., Schneider T., Smith A.K., Smith S.A., Cohen-Adad J., Gandini Wheeler-Kingshott C.A.M. ZOOM or Non-ZOOM? Assessing Spinal Cord Diffusion Tensor Imaging Protocols for Multi-Centre Studies. PLoS ONE. 2016;11:e0155557. doi: 10.1371/journal.pone.0155557. PubMed DOI PMC

Martin A.R., De Leener B., Cohen-Adad J., Cadotte D.W., Kalsi-Ryan S., Lange S.F., Tetreault L., Nouri A., Crawley A., Mikulis D.J., et al. Clinically Feasible Microstructural MRI to Quantify Cervical Spinal Cord Tissue Injury Using DTI, MT, and T2*-Weighted Imaging: Assessment of Normative Data and Reliability. AJNR Am. J. Neuroradiol. 2017;38:1257–1265. doi: 10.3174/ajnr.A5163. PubMed DOI PMC

Andersson J.L.R., Skare S., Ashburner J. How to correct susceptibility distortions in spin-echo echo-planar images: Application to diffusion tensor imaging. Neuroimage. 2003;20:870–888. doi: 10.1016/S1053-8119(03)00336-7. PubMed DOI

Andersson J.L.R., Sotiropoulos S.N. An integrated approach to correction for off-resonance effects and subject movement in diffusion MR imaging. Neuroimage. 2016;125:1063–1078. doi: 10.1016/j.neuroimage.2015.10.019. PubMed DOI PMC

Tuch D.S., Reese T.G., Wiegell M.R., Makris N., Belliveau J.W., Van Wedeen J. High angular resolution diffusion imaging reveals intravoxel white matter fiber heterogeneity. Magn. Reson. Med. 2002;48:577–582. doi: 10.1002/mrm.10268. PubMed DOI

Caruyer E., Lenglet C., Sapiro G., Deriche R. Design of multishell sampling schemes with uniform coverage in diffusion MRI. Magn. Reson. Med. 2013;69:1534–1540. doi: 10.1002/mrm.24736. PubMed DOI PMC

Deelchand D.K., Ho M.-L., Nestrasil I. Ultra-High-Field Imaging of the Pediatric Brain and Spinal Cord. Magn. Reson. Imaging Clin. N. Am. 2021;29:643–653. doi: 10.1016/j.mric.2021.06.013. PubMed DOI

Roussel T., Le Fur Y., Guye M., Viout P., Ranjeva J., Callot V. Respiratory-triggered quantitative MR spectroscopy of the human cervical spinal cord at 7 T. Magn. Reson. Med. 2022;87:2600–2612. doi: 10.1002/mrm.29182. PubMed DOI

Juchem C., Cudalbu C., Graaf R.A., Gruetter R., Henning A., Hetherington H.P., Boer V.O. B 0 shimming for in vivo magnetic resonance spectroscopy: Experts’ consensus recommendations. NMR Biomed. 2021;34:e4350. doi: 10.1002/nbm.4350. PubMed DOI

Andronesi O.C., Bhattacharyya P.K., Bogner W., Choi I., Hess A.T., Lee P., Meintjes E.M., Tisdall M.D., Zaitsev M., Kouwe A. Motion correction methods for MRS: Experts’ consensus recommendations. NMR Biomed. 2021;34:e4364. doi: 10.1002/nbm.4364. PubMed DOI PMC

Deelchand D.K., Henry P., Joers J.M., Auerbach E.J., Park Y.W., Kara F., Ratai E., Kantarci K., Öz G. Plug-and-play advanced magnetic resonance spectroscopy. Magn. Reson. Med. 2022;87:2613–2620. doi: 10.1002/mrm.29164. PubMed DOI PMC

De Leener B., Fonov V.S., Collins D.L., Callot V., Stikov N., Cohen-Adad J. PAM50: Unbiased multimodal template of the brainstem and spinal cord aligned with the ICBM152 space. Neuroimage. 2018;165:170–179. doi: 10.1016/j.neuroimage.2017.10.041. PubMed DOI

De Leener B., Lévy S., Dupont S.M., Fonov V.S., Stikov N., Louis Collins D., Callot V., Cohen-Adad J. SCT: Spinal Cord Toolbox, an open-source software for processing spinal cord MRI data. Neuroimage. 2017;145:24–43. doi: 10.1016/j.neuroimage.2016.10.009. PubMed DOI

McLachlin S., Leung J., Sivan V., Quirion P., Wilkie P., Cohen-Adad J., Whyne C.M., Hardisty M.R. Spatial correspondence of spinal cord white matter tracts using diffusion tensor imaging, fibre tractography, and atlas-based segmentation. Neuroradiology. 2021;63:373–380. doi: 10.1007/s00234-021-02635-9. PubMed DOI

Dostál M., Keřkovský M., Staffa E., Bednařík J., Šprláková-Puková A., Mechl M. Voxelwise analysis of diffusion MRI of cervical spinal cord using tract-based spatial statistics. Magn. Reson. Imaging. 2020;73:23–30. doi: 10.1016/j.mri.2020.07.008. PubMed DOI

Gros C., De Leener B., Badji A., Maranzano J., Eden D., Dupont S.M., Talbott J., Zhuoquiong R., Liu Y., Granberg T., et al. Automatic segmentation of the spinal cord and intramedullary multiple sclerosis lesions with convolutional neural networks. Neuroimage. 2019;184:901–915. doi: 10.1016/j.neuroimage.2018.09.081. PubMed DOI PMC

Perone C.S., Calabrese E., Cohen-Adad J. Spinal cord gray matter segmentation using deep dilated convolutions. Sci. Rep. 2018;8:5966. doi: 10.1038/s41598-018-24304-3. PubMed DOI PMC

Jenkinson M., Beckmann C.F., Behrens T.E.J., Woolrich M.W., Smith S.M. FSL. Neuroimage. 2012;62:782–790. doi: 10.1016/j.neuroimage.2011.09.015. PubMed DOI

Penny W., Friston K., Ashburner J., Kiebel S., Nichols T. Statistical Parametric Mapping. Elsevier; Amsterdam, The Netherlands: 2007.

Garyfallidis E., Brett M., Amirbekian B., Rokem A., van der Walt S., Descoteaux M., Nimmo-Smith I. Dipy, a library for the analysis of diffusion MRI data. Front. Neuroinform. 2014;8:8. doi: 10.3389/fninf.2014.00008. PubMed DOI PMC

Provencher S.W. Estimation of metabolite concentrations from localized in vivo proton NMR spectra. Magn. Reson. Med. 1993;30:672–679. doi: 10.1002/mrm.1910300604. PubMed DOI

Li X., Morgan P.S., Ashburner J., Smith J., Rorden C. The first step for neuroimaging data analysis: DICOM to NIfTI conversion. J. Neurosci. Methods. 2016;264:47–56. doi: 10.1016/j.jneumeth.2016.03.001. PubMed DOI

Tetreault L., Kopjar B., Nouri A., Arnold P., Barbagallo G., Bartels R., Qiang Z., Singh A., Zileli M., Vaccaro A., et al. The modified Japanese Orthopaedic Association scale: Establishing criteria for mild, moderate and severe impairment in patients with degenerative cervical myelopathy. Eur. Spine J. 2017;26:78–84. doi: 10.1007/s00586-016-4660-8. PubMed DOI

Holly L.T., Freitas B., McArthur D.D.L., Salamon N. Proton magnetic resonance spectroscopy to evaluate spinal cord axonal injury in cervical spondylotic myelopathy: Laboratory investigation. J. Neurosurg. Spine. 2009;10:194–200. doi: 10.3171/2008.12.SPINE08367. PubMed DOI

Evidence-based commentary on the diagnosis, management, and further research of degenerative cervical spinal cord compression in the absence of clinical symptoms of myelopathy