Skip to main content

Advertisement

SpringerLink
Log in

Potential of neuroimaging as a biomarker in amyotrophic lateral sclerosis: from structure to metabolism

  • Review
  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by motor neuron degeneration. The development of ALS involves metabolite alterations leading to tissue lesions in the nervous system. Recent advances in neuroimaging have significantly improved our understanding of the underlying pathophysiology of ALS, with findings supporting the corticoefferent axonal disease progression theory. Current studies on neuroimaging in ALS have demonstrated inconsistencies, which may be due to small sample sizes, insufficient statistical power, overinterpretation of findings, and the inherent heterogeneity of ALS. Deriving meaningful conclusions solely from individual imaging metrics in ALS studies remains challenging, and integrating multimodal imaging techniques shows promise for detecting valuable ALS biomarkers. In addition to giving an overview of the principles and techniques of different neuroimaging modalities, this review describes the potential of neuroimaging biomarkers in the diagnosis and prognostication of ALS. We provide an insight into the underlying pathology, highlighting the need for standardized protocols and multicenter collaborations to advance ALS research.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Data availability

Not applicable.

References

  1. Abdulla S, Machts J, Kaufmann J, Patrick K, Kollewe K, Dengler R, Heinze HJ, Petri S, Vielhaber S, Nestor PJ (2014) Hippocampal degeneration in patients with amyotrophic lateral sclerosis. Neurobiol Aging 35:2639–2645. https://doi.org/10.1016/j.neurobiolaging.2014.05.035

    Article  PubMed  Google Scholar 

  2. Abhinav K, Yeh F-C, El-Dokla A, Ferrando LM, Chang Y-F, Lacomis D, Friedlander RM, Fernandez-Miranda JC (2014) Use of diffusion spectrum imaging in preliminary longitudinal evaluation of amyotrophic lateral sclerosis: development of an imaging biomarker. Front Human Neurosci 8:270. https://doi.org/10.3389/fnhum.2014.00270

    Article  Google Scholar 

  3. Adachi Y, Sato N, Saito Y, Kimura Y, Nakata Y, Ito K, Kamiya K, Matsuda H, Tsukamoto T, Ogawa M (2015) Usefulness of SWI for the detection of iron in the motor cortex in amyotrophic lateral sclerosis. J Neuroimaging 25:443–451. https://doi.org/10.1111/jon.12127

    Article  PubMed  Google Scholar 

  4. Ahmed H, Wallimann R, Haider A, Hosseini V, Gruber S, Robledo M, Nguyen TAN, Herde AM, Iten I, Keller C, Vogel V, Schibli R, Wünsch B, Mu L, Ametamey SM (2021) Preclinical Development of (18)F-OF-NB1 for Imaging GluN2B-Containing N-Methyl-d-Aspartate Receptors and Its Utility as a Biomarker for Amyotrophic Lateral Sclerosis. J Nucl Med 62:259–265. https://doi.org/10.2967/jnumed.120.246785

    Article  CAS  PubMed  Google Scholar 

  5. Ahmed RM, Bocchetta M, Todd EG, Tse NY, Devenney EM, Tu S, Caga J, Hodges JR, Halliday GM, Irish M, Kiernan MC, Piguet O, Rohrer JD (2021) Tackling clinical heterogeneity across the amyotrophic lateral sclerosis-frontotemporal dementia spectrum using a transdiagnostic approach. Brain Commun 3. https://doi.org/10.1093/braincomms/fcab257

  6. Alruwaili AR, Pannek K, Coulthard A, Henderson R, Kurniawan ND, McCombe P (2018) A combined tract-based spatial statistics and voxel-based morphometry study of the first MRI scan after diagnosis of amyotrophic lateral sclerosis with subgroup analysis. J Neuroradiol 45:41–48. https://doi.org/10.1016/j.neurad.2017.03.007

  7. Babu S, Hightower BG, Chan J, Zürcher NR, Kivisäkk P, Tseng CJ, Sanders DL, Robichaud A, Banno H, Evora A, Ashokkumar A, Pothier L, Paganoni S, Chew S, Dojillo J, Matsuda K, Gudesblatt M, Berry JD, Cudkowicz ME, Hooker JM, Atassi N (2021) Ibudilast (MN-166) in amyotrophic lateral sclerosis- an open label, safety and pharmacodynamic trial. NeuroImage Clin 30:102672. https://doi.org/10.1016/j.nicl.2021.102672

    Article  PubMed  PubMed Central  Google Scholar 

  8. Baek SH, Park J, Kim YH, Seok HY, Oh KW, Kim HJ, Kwon YJ, Sim Y, Tae WS, Kim SH, Kim BJ (2020) Usefulness of diffusion tensor imaging findings as biomarkers for amyotrophic lateral sclerosis. Sci Rep 10:5199. https://doi.org/10.1038/s41598-020-62049-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Bao Y, Chen Y, Piao S, Hu B, Yang L, Li H, Geng D, Li Y (2023) Iron quantitative analysis of motor combined with bulbar region in M1 cortex may improve diagnosis performance in ALS. Eur Radiol 33:1132–1142. https://doi.org/10.1007/s00330-022-09045-2

    Article  PubMed  Google Scholar 

  10. Bao Y, Yang L, Chen Y, Zhang B, Li H, Tang W, Geng D, Li Y (2018) Radial diffusivity as an imaging biomarker for early diagnosis of non-demented amyotrophic lateral sclerosis. Eur Radiol 28:4940–4948. https://doi.org/10.1007/s00330-018-5506-z

    Article  PubMed  Google Scholar 

  11. Barry RL, Torrado-Carvajal A, Kirsch JE, Arabasz GE, Albrecht DS, Alshelh Z, Pijanowski O, Lewis AJ, Keegan M, Reynolds B, Knight PC, Morrissey EJ, Loggia ML, Atassi N, Hooker JM, Babu S (2022) Selective atrophy of the cervical enlargement in whole spinal cord MRI of amyotrophic lateral sclerosis. NeuroImage Clin 36:103199. https://doi.org/10.1016/j.nicl.2022.103199

    Article  PubMed  PubMed Central  Google Scholar 

  12. Bayer D, Antonucci S, Müller HP, Saad R, Dupuis L, Rasche V, Böckers TM, Ludolph AC, Kassubek J, Roselli F (2021) Disruption of orbitofrontal-hypothalamic projections in a murine ALS model and in human patients. Trans Neurodegeneration 10:17. https://doi.org/10.1186/s40035-021-00241-6

    Article  Google Scholar 

  13. Behler A, Müller HP, Ludolph AC, Kassubek J (2023) Diffusion Tensor Imaging in Amyotrophic Lateral Sclerosis: Machine Learning for Biomarker Development. Int J Mol Sci 24. https://doi.org/10.3390/ijms24031911

  14. Behler A, Müller HP, Ludolph AC, Lulé D, Kassubek J (2022) A multivariate Bayesian classification algorithm for cerebral stage prediction by diffusion tensor imaging in amyotrophic lateral sclerosis. NeuroImage Clin 35:103094. https://doi.org/10.1016/j.nicl.2022.103094

    Article  PubMed  PubMed Central  Google Scholar 

  15. Bharti K, Khan M, Beaulieu C, Graham SJ, Briemberg H, Frayne R, Genge A, Korngut L, Zinman L, Kalra S (2020) Involvement of the dentate nucleus in the pathophysiology of amyotrophic lateral sclerosis: a multi-center and multi-modal neuroimaging study. NeuroImage Clin 28:102385. https://doi.org/10.1016/j.nicl.2020.102385

    Article  PubMed  PubMed Central  Google Scholar 

  16. Bhattarai A, Chen Z, Ward PGD, Talman P, Mathers S, Phan TG, Chapman C, Howe J, Lee S, Lie Y, Egan GF, Chua P (2020) Serial assessment of iron in the motor cortex in limb-onset amyotrophic lateral sclerosis using quantitative susceptibility mapping. Quantitative imaging in medicine and surgery 10:1465–1476. https://doi.org/10.21037/qims-20-187

  17. Bhattarai A, Egan GF, Talman P, Chua P, Chen Z (2022) Magnetic resonance iron imaging in amyotrophic lateral sclerosis. J Magn Reson Imaging 55:1283–1300. https://doi.org/10.1002/jmri.27530

    Article  PubMed  Google Scholar 

  18. Braak H, Brettschneider J, Ludolph AC, Lee VM, Trojanowski JQ, Tredici KD (2013) Amyotrophic lateral sclerosis—a model of corticofugal axonal spread. Nat Rev Neurol 9:708–714. https://doi.org/10.1038/nrneurol.2013.221

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Broad RJ, Gabel MC, Dowell NG, Schwartzman DJ, Seth AK, Zhang H, Alexander DC, Cercignani M, Leigh PN (2019) Neurite orientation and dispersion density imaging (NODDI) detects cortical and corticospinal tract degeneration in ALS. J Neurol Neurosurg Psychiatry 90:404–411. https://doi.org/10.1136/jnnp-2018-318830

    Article  PubMed  Google Scholar 

  20. Bueno APA, Pinaya WHL, Moura LM, Bertoux M, Radakovic R, Kiernan MC, Teixeira AL, de Souza LC, Hornberger M, Sato JR (2018) Structural and functional papez circuit integrity in amyotrophic lateral sclerosis. Brain Imaging Behav 12:1622–1630. https://doi.org/10.1007/s11682-018-9825-0

    Article  PubMed  Google Scholar 

  21. Caldwell S, Rothman DL (2021) (1)H Magnetic resonance spectroscopy to understand the biological basis of ALS, diagnose patients earlier, and monitor disease progression. Front Neurol 12:701170. https://doi.org/10.3389/fneur.2021.701170

    Article  PubMed  PubMed Central  Google Scholar 

  22. Calvo A, Canosa A, Moglia C, Manera U, Grassano M, Vasta R, Palumbo F, Cugnasco P, Gallone S, Brunetti M, De Marchi F, Arena V, Pagani M, Dalgard C, Scholz SW, Chia R, Corrado L, Dalfonso S, Mazzini L, Traynor BJ, Chio A (2022) Clinical and metabolic signature of UNC13A rs12608932 variant in amyotrophic lateral sclerosis. Neurol Genet 8:e200033. https://doi.org/10.1212/nxg.0000000000200033

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Canna A, Trojsi F, Di Nardo F, Caiazzo G, Tedeschi G, Cirillo M, Esposito F (2021) Combining structural and metabolic markers in a quantitative MRI study of motor neuron diseases. Ann Clin Transl Neurol 8:1774–1785. https://doi.org/10.1002/acn3.51418

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Canosa A, Calvo A, Moglia C, Manera U, Vasta R, Di Pede F, Cabras S, Nardo D, Arena V, Grassano M, D’Ovidio F, Van Laere K, Van Damme P, Pagani M, Chiò A (2021) Brain metabolic changes across King’s stages in amyotrophic lateral sclerosis: a (18)F-2-fluoro-2-deoxy-D-glucose-positron emission tomography study. Eur J Nucl Med Mol Imaging 48:1124–1133. https://doi.org/10.1007/s00259-020-05053-w

    Article  PubMed  Google Scholar 

  25. Canosa A, Calvo A, Moglia C, Vasta R, Palumbo F, Solero L, Di Pede F, Cabras S, Arena V, Zocco G, Casale F, Brunetti M, Sbaiz L, Gallone S, Grassano M, Manera U, Pagani M, Chiò A (2022) Amyotrophic lateral sclerosis with SOD1 mutations shows distinct brain metabolic changes. Eur J Nucl Med Mol Imaging 49:2242–2250. https://doi.org/10.1007/s00259-021-05668-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Canosa A, Martino A, Giuliani A, Moglia C, Vasta R, Grassano M, Palumbo F, Cabras S, Di Pede F, De Mattei F, Matteoni E, Polverari G, Manera U, Calvo A, Pagani M, Chiò A (2023) Brain metabolic differences between pure bulbar and pure spinal ALS: a 2-[(18)F]FDG-PET study. J Neurol 270:953–959. https://doi.org/10.1007/s00415-022-11445-9

    Article  CAS  PubMed  Google Scholar 

  27. Canosa A, Martino A, Manera U, Vasta R, Grassano M, Palumbo F, Cabras S, Di Pede F, Arena V, Moglia C, Giuliani A, Calvo A, Chiò A, Pagani M (2023) Role of brain 2-[(18)F]fluoro-2-deoxy-D-glucose-positron-emission tomography as survival predictor in amyotrophic lateral sclerosis. Eur J Nucl Med Mol Imaging 50:784–791. https://doi.org/10.1007/s00259-022-05987-3

    Article  CAS  PubMed  Google Scholar 

  28. Canosa A, Palumbo F, Iazzolino B, Peotta L, Di Pede F, Manera U, Vasta R, Grassano M, Solero L, Arena V, Moglia C, Calvo A, Chiò A, Pagani M (2021) The interplay among education, brain metabolism, and cognitive impairment suggests a role of cognitive reserve in Amyotrophic Lateral Sclerosis. Neurobiol Aging 98:205–213. https://doi.org/10.1016/j.neurobiolaging.2020.11.010

    Article  CAS  PubMed  Google Scholar 

  29. Canosa A, Vacchiano V, D’Ovidio F, Calvo A, Moglia C, Manera U, Vasta R, Liguori R, Arena V, Grassano M, Palumbo F, Peotta L, Iazzolino B, Pagani M, Chiò A (2021) Brain metabolic correlates of apathy in amyotrophic lateral sclerosis: an 18F-FDG-positron emission tomography stud. Eur J Neurol 28:745–753. https://doi.org/10.1111/ene.14637

    Article  PubMed  Google Scholar 

  30. Cervo A, Cocozza S, Saccà F, Giorgio S, Morra VB, Tedeschi E, Marsili A, Vacca G, Palma V, Brunetti A, Quarantelli M (2015) The combined use of conventional MRI and MR spectroscopic imaging increases the diagnostic accuracy in amyotrophic lateral sclerosis. Eur J Radiol 84:151–157. https://doi.org/10.1016/j.ejrad.2014.10.019

    Article  PubMed  Google Scholar 

  31. Chen HJ, Zhan C, Cai LM, Lin JH, Zhou MX, Zou ZY, Yao XF, Lin YJ (2021) White matter microstructural impairments in amyotrophic lateral sclerosis: a mean apparent propagator MRI study. NeuroImage Clinical 32:102863. https://doi.org/10.1016/j.nicl.2021.102863

    Article  PubMed  PubMed Central  Google Scholar 

  32. Chenji S, Ishaque A, Mah D, Fujiwara E, Beaulieu C, Seres P, Graham SJ, Frayne R, Zinman L, Genge A, Korngut L, Johnston W, Kalra S (2021) Neuroanatomical associations of the Edinburgh cognitive and Behavioural ALS screen (ECAS). Brain Imaging Behav 15:1641–1654. https://doi.org/10.1007/s11682-020-00359-7

    Article  PubMed  Google Scholar 

  33. Chipika RH, Christidi F, Finegan E, Li Hi Shing S, McKenna MC, Chang KM, Karavasilis E, Doherty MA, Hengeveld JC, Vajda A, Pender N, Hutchinson S, Donaghy C, McLaughlin RL, Hardiman O, Bede P (2020) Amygdala pathology in amyotrophic lateral sclerosis and primary lateral sclerosis. J Neurol Sci 417. https://doi.org/10.1016/j.jns.2020.117039

  34. Christidi F, Argyropoulos GD, Karavasilis E, Velonakis G, Zouvelou V, Kourtesis P, Pantoleon V, Tan EL, Daponte A, Aristeidou S, Xirou S, Ferentinos P, Evdokimidis I, Rentzos M, Seimenis I, Bede P (2023) Hippocampal Metabolic Alterations in Amyotrophic Lateral Sclerosis: A Magnetic Resonance Spectroscopy Study. Life (Basel, Switzerland) 13. https://doi.org/10.3390/life13020571

  35. Chung HS, Melkus G, Bourque P, Chakraborty S (2023) Motor band sign in motor neuron disease: a marker for upper motor neuron involvement. Can J Neurol Sci 50:373–379. https://doi.org/10.1017/cjn.2022.52

    Article  PubMed  Google Scholar 

  36. Consonni M, Cappa SF, Dalla Bella E, Contarino VE, Lauria G (2019) Cortical correlates of behavioural change in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 90:380–386. https://doi.org/10.1136/jnnp-2018-318619

    Article  PubMed  Google Scholar 

  37. Consonni M, Dalla Bella E, Contarino VE, Bersano E, Lauria G (2020) Cortical thinning trajectories across disease stages and cognitive impairment in amyotrophic lateral sclerosis. Cortex 131:284–294. https://doi.org/10.1016/j.cortex.2020.07.007

    Article  PubMed  Google Scholar 

  38. Contarino VE, Conte G, Morelli C, Trogu F, Scola E, Calloni SF, Sanmiguel Serpa LC, Liu C, Silani V, Triulzi F (2020) Toward a marker of upper motor neuron impairment in amyotrophic lateral sclerosis: a fully automatic investigation of the magnetic susceptibility in the precentral cortex. Eur J Radiol 124:108815. https://doi.org/10.1016/j.ejrad.2020.108815

    Article  PubMed  Google Scholar 

  39. Conte G, Sbaraini S, Morelli C, Casale S, Caschera L, Contarino VE, Scola E, Cinnante C, Trogu F, Triulzi F, Silani V (2021) A susceptibility-weighted imaging qualitative score of the motor cortex may be a useful tool for distinguishing clinical phenotypes in amyotrophic lateral sclerosis. Eur Radiol 31:1281–1289. https://doi.org/10.1007/s00330-020-07239-0

    Article  CAS  PubMed  Google Scholar 

  40. Costagli M, Donatelli G, Biagi L, Caldarazzo Ienco E, Siciliano G, Tosetti M, Cosottini M (2016) Magnetic susceptibility in the deep layers of the primary motor cortex in amyotrophic lateral sclerosis. NeuroImage Clinical 12:965–969. https://doi.org/10.1016/j.nicl.2016.04.011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Crespi C, Dodich A, Iannaccone S, Marcone A, Falini A, Cappa SF, Cerami C (2020) Diffusion tensor imaging evidence of corticospinal pathway involvement in frontotemporal lobar degeneration. Cortex 125:1–11. https://doi.org/10.1016/j.cortex.2019.11.022

    Article  PubMed  Google Scholar 

  42. de Carvalho M, Turkman A, Swash M (2003) Motor responses evoked by transcranial magnetic stimulation and peripheral nerve stimulation in the ulnar innervation in amyotrophic lateral sclerosis: the effect of upper and lower motor neuron lesion. J NEUROL SCI 210:83–90

    Article  PubMed  Google Scholar 

  43. De Marchi F, Stecco A, Falaschi Z, Filippone F, Pasché A, Bebeti A, Leigheb M, Cantello R, Mazzini L (2020) Detection of White Matter Ultrastructural Changes for Amyotrophic Lateral Sclerosis Characterization: A Diagnostic Study from Dti-Derived Data. Brain sciences 10. https://doi.org/10.3390/brainsci10120996

  44. Dey A, Luk CC, Ishaque A, Ta D, Srivastava O, Krebs D, Seres P, Hanstock C, Beaulieu C, Korngut L, Frayne R, Zinman L, Graham S, Genge A, Briemberg H, Kalra S (2023) Motor cortex functional connectivity is associated with underlying neurochemistry in ALS. J Neurol Neurosurg Psychiatry 94:193–200. https://doi.org/10.1136/jnnp-2022-329993

    Article  PubMed  Google Scholar 

  45. Ellis CM, Simmons A, Jones DK, Bland J, Dawson JM, Horsfield MA, Williams SC, Leigh PN (1999) Diffusion tensor MRI assesses corticospinal tract damage in ALS. Neurology 53:1051–1058

    Article  CAS  PubMed  Google Scholar 

  46. Femiano C, Trojsi F, Caiazzo G, Siciliano M, Passaniti C, Russo A, Bisecco A, Cirillo M, Monsurrò MR, Esposito F, Tedeschi G, Santangelo G (2018) Apathy is correlated with widespread diffusion tensor imaging (DTI) impairment in amyotrophic lateral sclerosis. Behav Neurol 2018:2635202. https://doi.org/10.1155/2018/2635202

    Article  PubMed  PubMed Central  Google Scholar 

  47. Floeter MK, Danielian LE, Braun LE, Wu T (2018) Longitudinal diffusion imaging across the C9orf72 clinical spectrum. J Neurol Neurosurg Psychiatry 89:53–60. https://doi.org/10.1136/jnnp-2017-316799

    Article  PubMed  Google Scholar 

  48. Fukui Y, Hishikawa N, Sato K, Nakano Y, Morihara R, Shang J, Takemoto M, Ohta Y, Yamashita T, Abe K (2018) Detecting spinal pyramidal tract of amyotrophic lateral sclerosis patients with diffusion tensor tractography. Neurosci Res 133:58–63. https://doi.org/10.1016/j.neures.2017.11.005

    Article  PubMed  Google Scholar 

  49. García Santos JM, Inuggi A, Gómez Espuch J, Vázquez C, Iniesta F, Blanquer M, María Moraleda J, Martínez S (2016) Spinal cord infusion of stem cells in amyotrophic lateral sclerosis: Magnetic resonance spectroscopy shows metabolite improvement in the precentral gyrus. Cytotherapy 18:785–796. https://doi.org/10.1016/j.jcyt.2016.03.296

    Article  CAS  PubMed  Google Scholar 

  50. Gatto RG, Amin M, Finkielsztein A, Weissmann C, Barrett T, Lamoutte C, Uchitel O, Sumagin R, Mareci TH, Magin RL (2019) Unveiling early cortical and subcortical neuronal degeneration in ALS mice by ultra-high field diffusion MRI. Amyotroph Lateral Scler Frontotemporal Degener 20:549–561. https://doi.org/10.1080/21678421.2019.1620285

    Article  CAS  PubMed  Google Scholar 

  51. Ghaderi S, Fatehi F, Kalra S, Batouli SAH (2023) MRI biomarkers for memory-related impairment in amyotrophic lateral sclerosis: a systematic review. Amyotroph Lateral Scler Frontotemporal Degener:1–17. https://doi.org/10.1080/21678421.2023.2236651

  52. Gorges M, Del Tredici K, Dreyhaupt J, Braak H, Ludolph AC, Müller HP, Kassubek J (2018) Corticoefferent pathology distribution in amyotrophic lateral sclerosis: in vivo evidence from a meta-analysis of diffusion tensor imaging data. Sci Rep 8:15389. https://doi.org/10.1038/s41598-018-33830-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Grapperon A-M, Verschueren A, Jouve E, Morizot-Koutlidis R, Lenglet T, Pradat P-F, Salachas F, Bernard E, Delstanche S, Maertens de Noordhout A, Guy N, Danel V, Delval A, Delmont E, Rolland A-S, Pulse Study G, Jomir L, Devos D, Wang F, Attarian S (2021) Assessing the upper motor neuron in amyotrophic lateral sclerosis using the triple stimulation technique: A multicenter prospective study. Clin Neurophysiol 132:2551-2557. https://doi.org/10.1016/j.clinph.2021.08.003

  54. Higashihara M, Ishibashi K, Tokumaru AM, Iwata A, Ishii K (2021) 18F-THK5351 PET can identify core lesions in different amyotrophic lateral sclerosis phenotypes. Clin Nucl Med 46:e582–e583. https://doi.org/10.1097/rlu.0000000000003755

    Article  PubMed  Google Scholar 

  55. Huang NX, Qin W, Lin JH, Dong QY, Chen HJ (2023) Corticospinal fibers with different origins impair in amyotrophic lateral sclerosis: a neurite orientation dispersion and density imaging study. CNS Neurosci Ther. https://doi.org/10.1111/cns.14270

    Article  PubMed  PubMed Central  Google Scholar 

  56. Huang NX, Zou ZY, Xue YJ, Chen HJ (2020) Abnormal cerebral microstructures revealed by diffusion kurtosis imaging in amyotrophic lateral sclerosis. J Magn Reson Imaging 51:554–562. https://doi.org/10.1002/jmri.26843

    Article  PubMed  Google Scholar 

  57. Hübers A, Böckler B, Abaei A, Rasche V, Lulé D, Ercan E, Doorenweerd N, Müller HP, Dreyhaupt J, Kammer T, Ludolph AC, Ronen I, Kassubek J (2021) Functional and structural impairment of transcallosal motor fibres in ALS: a study using transcranial magnetic stimulation, diffusion tensor imaging, and diffusion weighted spectroscopy. Brain Imaging Behav 15:748–757. https://doi.org/10.1007/s11682-020-00282-x

    Article  PubMed  Google Scholar 

  58. Ishaque A, Mah D, Seres P, Luk C, Johnston W, Chenji S, Beaulieu C, Yang YH, Kalra S (2019) Corticospinal tract degeneration in ALS unmasked in T1-weighted images using texture analysis. Hum Brain Mapp 40:1174–1183. https://doi.org/10.1002/hbm.24437

    Article  PubMed  Google Scholar 

  59. Kalra S (2019) Magnetic resonance spectroscopy in ALS. Front Neurol 10:482. https://doi.org/10.3389/fneur.2019.00482

    Article  PubMed  PubMed Central  Google Scholar 

  60. Kassubek J, Müller HP, Del Tredici K, Brettschneider J, Pinkhardt EH, Lulé D, Böhm S, Braak H, Ludolph AC (2014) Diffusion tensor imaging analysis of sequential spreading of disease in amyotrophic lateral sclerosis confirms patterns of TDP-43 pathology. Brain 137:1733–1740. https://doi.org/10.1093/brain/awu090

    Article  PubMed  Google Scholar 

  61. Khamaysa M, Lefort M, Pélégrini-Issac M, Lackmy-Vallée A, Preuilh A, Devos D, Rolland AS, Desnuelle C, Chupin M, Marchand-Pauvert V, Querin G, Pradat PF (2023) Comparison of spinal magnetic resonance imaging and classical clinical factors in predicting motor capacity in amyotrophic lateral sclerosis. J Neurol 270:3885–3895. https://doi.org/10.1007/s00415-023-11727-w

    Article  CAS  PubMed  Google Scholar 

  62. Kiernan JA, Hudson AJ (1991) Changes in sizes of cortical and lower motor neurons in amyotrophic lateral sclerosis. Brain : a Journal of Neurology 114(Pt 2):843–853

    Article  PubMed  Google Scholar 

  63. Knight AC, Morrone CD, Varlow C, Yu WH, McQuade P, Vasdev N (2023) Head-to-head comparison of Tau-PET radioligands for imaging TDP-43 in post-mortem ALS brain. Mol Imag Biol 25:513–527. https://doi.org/10.1007/s11307-022-01779-1

    Article  CAS  Google Scholar 

  64. Kocar TD, Behler A, Ludolph AC, Müller HP, Kassubek J (2021) Multiparametric microstructural MRI and machine learning classification yields high diagnostic accuracy in amyotrophic lateral sclerosis: proof of concept. Front Neurol 12:745475. https://doi.org/10.3389/fneur.2021.745475

    Article  PubMed  PubMed Central  Google Scholar 

  65. Kocar TD, Müller HP, Ludolph AC, Kassubek J (2021) Feature selection from magnetic resonance imaging data in ALS: a systematic review. Therapeutic Adv Chronic Dis 12:20406223211051000. https://doi.org/10.1177/20406223211051002

    Article  Google Scholar 

  66. Krieger C, Kalra S (2023) Imaging the amyotrophic lateral sclerosis brain: the motor band sign. Can J Neurol Sci 50:327–328. https://doi.org/10.1017/cjn.2022.67

    Article  PubMed  Google Scholar 

  67. Kumar JSD, Molotkov A, Kim J, Carberry P, Idumonyi S, Castrillon J, Duff K, Shneider NA, Mintz A (2022) Preclinical evaluation of a microtubule PET ligand [(11)C]MPC-6827 in tau and amyotrophic lateral sclerosis animal models. Pharmacol Rep 74:539–544. https://doi.org/10.1007/s43440-022-00359-y

    Article  CAS  PubMed  Google Scholar 

  68. Kwong LK, Neumann M, Sampathu DM, Lee VMY, Trojanowski JQ (2007) TDP-43 proteinopathy: the neuropathology underlying major forms of sporadic and familial frontotemporal lobar degeneration and motor neuron disease. Acta Neuropathol 114:63–70

    Article  CAS  PubMed  Google Scholar 

  69. Lai TW, Zhang S, Wang YT (2014) Excitotoxicity and stroke: identifying novel targets for neuroprotection. Prog Neurobiol 115:157–188. https://doi.org/10.1016/j.pneurobio.2013.11.006

    Article  CAS  PubMed  Google Scholar 

  70. Li H, Zhang Q, Duan Q, Jin J, Hu F, Dang J, Zhang M (2021) Brainstem involvement in amyotrophic lateral sclerosis: a combined structural and diffusion tensor MRI analysis. Front Neurosci 15:675444. https://doi.org/10.3389/fnins.2021.675444

    Article  PubMed  PubMed Central  Google Scholar 

  71. Li Q, Zhu W, Wen X, Zang Z, Da Y, Lu J (2022) Beyond the motor cortex: thalamic iron deposition accounts for disease severity in amyotrophic lateral sclerosis. Front Neurol 13:791300. https://doi.org/10.3389/fneur.2022.791300

    Article  PubMed  PubMed Central  Google Scholar 

  72. Li Q, Zhu W, Wen X, Zang Z, Da Y, Lu J (2022) Different sensorimotor mechanism in fast and slow progression amyotrophic lateral sclerosis. Hum Brain Mapp 43:1710–1719. https://doi.org/10.1002/hbm.25752

    Article  PubMed  Google Scholar 

  73. Li W, Zhao Z, Liu M, Yan S, An Y, Qiao L, Wang G, Qi Z, Lu J (2022) Multimodal classification of alzheimer’s disease and amnestic mild cognitive impairment: integrated 18F-FDG PET and DTI study. J Alzheimers Dis 85:1063–1075. https://doi.org/10.3233/JAD-215338

    Article  CAS  PubMed  Google Scholar 

  74. Liu P, Tang Y, Li W, Liu Z, Zhou M, Li J, Yuan Y, Fang L, Guo J, Shen L, Jiang H, Tang B, Hu S, Wang J (2023) Brain metabolic signatures in patients with genetic and nongenetic amyotrophic lateral sclerosis. CNS Neurosci Ther 29:2530–2539. https://doi.org/10.1111/cns.14193

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Liu S, Buch S, Chen Y, Choi H-S, Dai Y, Habib C, Hu J, Jung J-Y, Luo Y, Utriainen D, Wang M, Wu D, Xia S, Haacke EM (2017) Susceptibility-weighted imaging: current status and future directions. NMR in biomedicine 30. https://doi.org/10.1002/nbm.3552

  76. Machts J, Keute M, Kaufmann J, Schreiber S, Kasper E, Petri S, Prudlo J, Vielhaber S, Schoenfeld MA (2021) Longitudinal clinical and neuroanatomical correlates of memory impairment in motor neuron disease. NeuroImage Clin 29. https://doi.org/10.1016/j.nicl.2020.102545

  77. Maj E, Jamroży M, Bielecki M, Bartoszek M, Gołębiowski M, Wojtaszek M, Kuźma-Kozakiewicz M (2022) Role of DTI-MRI parameters in diagnosis of ALS: useful biomarkers for daily practice? Tertiary centre experience and literature review. Neurol Neurochir Pol 56:490–498. https://doi.org/10.5603/PJNNS.a2022.0070

    Article  PubMed  Google Scholar 

  78. Makary MM, Weerasekara A, Rodham H, Hightower BG, Tseng CJ, Chan J, Chew S, Paganoni S, Ratai EM, Zürcher NR, Hooker JM, Atassi N, Babu S (2021) Comparison of two clinical upper motor neuron burden rating scales in ALS using quantitative brain imaging. ACS Chem Neurosci 12:906–916. https://doi.org/10.1021/acschemneuro.0c00772

    Article  CAS  PubMed  Google Scholar 

  79. Marin B, Logroscino G, Boumédiene F, Labrunie A, Couratier P, Babron M-C, Leutenegger AL, Preux PM, Beghi E (2016) Clinical and demographic factors and outcome of amyotrophic lateral sclerosis in relation to population ancestral origin. Eur J Epidemiol 31:229–245. https://doi.org/10.1007/s10654-015-0090-x

    Article  PubMed  Google Scholar 

  80. Marini C, Cossu V, Kumar M, Milanese M, Cortese K, Bruno S, Bellese G, Carta S, Zerbo RA, Torazza C, Bauckneht M, Venturi C, Raffa S, Orengo AM, Donegani MI, Chiola S, Ravera S, Castellani P, Morbelli S, Sambuceti G, Bonanno G (2021) The Role of Endoplasmic Reticulum in the Differential Endurance against Redox Stress in Cortical and Spinal Astrocytes from the Newborn SOD1(G93A) Mouse Model of Amyotrophic Lateral Sclerosis. Antioxidants (Basel, Switzerland) 10. https://doi.org/10.3390/antiox10091392

  81. Matías-Guiu JA, Pytel V, Cabrera-Martín MN, Galán L, Valles-Salgado M, Guerrero A, Moreno-Ramos T, Matías-Guiu J, Carreras JL (2016) Amyloid- and FDG-PET imaging in amyotrophic lateral sclerosis. Eur J Nucl Med Mol Imaging 43:2050–2060. https://doi.org/10.1007/s00259-016-3434-1

    Article  CAS  PubMed  Google Scholar 

  82. Müller Herde A, Schibli R, Weber M, Ametamey SM (2019) Metabotropic glutamate receptor subtype 5 is altered in LPS-induced murine neuroinflammation model and in the brains of AD and ALS patients. Eur J Nucl Med Mol Imaging 46:407–420. https://doi.org/10.1007/s00259-018-4179-9

    Article  CAS  PubMed  Google Scholar 

  83. Nigri A, Dalla Bella E, Ferraro S, Medina Carrion JP, Demichelis G, Bersano E, Consonni M, Bischof A, Stanziano M, Palermo S, Lauria G, Bruzzone MG, Papinutto N (2023) Cervical spinal cord atrophy in amyotrophic lateral sclerosis across disease stages. Ann Clin Transl Neurol 10:213–224. https://doi.org/10.1002/acn3.51712

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Pagani M, Öberg J, De Carli F, Calvo A, Moglia C, Canosa A, Nobili F, Morbelli S, Fania P, Cistaro A, Chiò A (2016) Metabolic spatial connectivity in amyotrophic lateral sclerosis as revealed by independent component analysis. Hum Brain Mapp 37:942–953. https://doi.org/10.1002/hbm.23078

    Article  PubMed  Google Scholar 

  85. Paganoni S, Alshikho MJ, Luppino S, Chan J, Pothier L, Schoenfeld D, Andres PL, Babu S, Zürcher NR, Loggia ML, Barry RL, Luotti S, Nardo G, Trolese MC, Pantalone S, Bendotti C, Bonetto V, De Marchi F, Rosen B, Hooker J, Cudkowicz M, Atassi N (2019) A pilot trial of RNS60 in amyotrophic lateral sclerosis. Muscle Nerve 59:303–308. https://doi.org/10.1002/mus.26385

    Article  CAS  PubMed  Google Scholar 

  86. Prell T, Hartung V, Tietz F, Penzlin S, Ilse B, Schweser F, Deistung A, Bokemeyer M, Reichenbach JR, Witte OW, Grosskreutz J (2015) Susceptibility-weighted imaging provides insight into white matter damage in amyotrophic lateral sclerosis. PLoS ONE 10:e0131114. https://doi.org/10.1371/journal.pone.0131114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Qin Y, Zhang S, Jiang R, Gao F, Tang X, Zhu W (2018) Region-specific atrophy of precentral gyrus in patients with amyotrophic lateral sclerosis. J Magn Reson Imaging 47:115–122. https://doi.org/10.1002/jmri.25765

    Article  PubMed  Google Scholar 

  88. Rajagopalan V, Pioro EP (2020) 2-Deoxy-2-[(18) F]fluoro-d-glucose positron emission tomography, cortical thickness and white matter graph network abnormalities in brains of patients with amyotrophic lateral sclerosis and frontotemporal dementia suggest early neuronopathy rather than axonopathy. Eur J Neurol 27:1904–1912. https://doi.org/10.1111/ene.14332

    Article  CAS  PubMed  Google Scholar 

  89. Rajagopalan V, Pioro EP (2015) Comparing brain structural MRI and metabolic FDG-PET changes in patients with ALS-FTD: “the chicken or the egg?” question. J Neurol Neurosurg Psychiatry 86:952–958. https://doi.org/10.1136/jnnp-2014-308239

    Article  PubMed  Google Scholar 

  90. Reischauer C, Gutzeit A, Neuwirth C, Fuchs A, Sartoretti-Schefer S, Weber M, Czell D (2018) In-vivo evaluation of neuronal and glial changes in amyotrophic lateral sclerosis with diffusion tensor spectroscopy. NeuroImage Clinical 20:993–1000. https://doi.org/10.1016/j.nicl.2018.10.001

    Article  PubMed  PubMed Central  Google Scholar 

  91. Rizzo G, Marliani AF, Battaglia S, Albini Riccioli L, De Pasqua S, Vacchiano V, Infante R, Avoni P, Donadio V, Passaretti M, Bartolomei I, Salvi F, Liguori R, On Behalf Of The BoRe ALSG (2020) Diagnostic and Prognostic Value of Conventional Brain MRI in the Clinical Work-Up of Patients with Amyotrophic Lateral Sclerosis. J Clin Med 9. https://doi.org/10.3390/jcm9082538

  92. Roeben B, Wilke C, Bender B, Ziemann U, Synofzik M (2019) The motor band sign in ALS: presentations and frequencies in a consecutive series of ALS patients. J Neurol Sci 406:116440. https://doi.org/10.1016/j.jns.2019.116440

    Article  PubMed  Google Scholar 

  93. Romano A, Trosi Lopez E, Liparoti M, Polverino A, Minino R, Trojsi F, Bonavita S, Mandolesi L, Granata C, Amico E, Sorrentino G, Sorrentino P (2022) The progressive loss of brain network fingerprints in Amyotrophic Lateral Sclerosis predicts clinical impairment. NeuroImage Clin 35:103095. https://doi.org/10.1016/j.nicl.2022.103095

    Article  PubMed  PubMed Central  Google Scholar 

  94. Saitoh Y, Imabayashi E, Mukai T, Matsuda H, Takahashi Y (2021) Visualization of motor cortex involvement by 18F-THK5351 PET potentially strengthens diagnosis of amyotrophic lateral sclerosis. Clin Nucl Med 46:243–245. https://doi.org/10.1097/rlu.0000000000003456

    Article  PubMed  Google Scholar 

  95. Sako W, Izumi Y, Abe T, Haji S, Murakami N, Osaki Y, Matsumoto Y, Harada M, Kaji R (2021) MR spectroscopy and imaging-derived measurements in the supplementary motor area for biomarkers of amyotrophic lateral sclerosis. Neurol Sci 42:4257–4263. https://doi.org/10.1007/s10072-021-05107-3

    Article  PubMed  Google Scholar 

  96. Sala A, Iaccarino L, Fania P, Vanoli EG, Fallanca F, Pagnini C, Cerami C, Calvo A, Canosa A, Pagani M, Chiò A, Cistaro A, Perani D (2019) Testing the diagnostic accuracy of [18F]FDG-PET in discriminating spinal- and bulbar-onset amyotrophic lateral sclerosis. Eur J Nucl Med Mol Imaging 46:1117–1131. https://doi.org/10.1007/s00259-018-4246-2

    Article  PubMed  Google Scholar 

  97. Sarica A, Valentino P, Nisticò R, Barone S, Pucci F, Quattrone A, Cerasa A, Quattrone A (2019) Assessment of the corticospinal tract profile in pure lower motor neuron disease: a diffusion tensor imaging study. Neurodegener Dis 19:128–138. https://doi.org/10.1159/000503970

    Article  PubMed  Google Scholar 

  98. Sassani M, Alix JJ, McDermott CJ, Baster K, Hoggard N, Wild JM, Mortiboys HJ, Shaw PJ, Wilkinson ID, Jenkins TM (2020) Magnetic resonance spectroscopy reveals mitochondrial dysfunction in amyotrophic lateral sclerosis. Brain 143:3603–3618. https://doi.org/10.1093/brain/awaa340

    Article  PubMed  Google Scholar 

  99. Sennfält S, Pagani M, Fang F, Savitcheva I, Estenberg U, Ingre C (2023) FDG-PET shows weak correlation between focal motor weakness and brain metabolic alterations in ALS. Amyotroph Lateral Scler Frontotemporal Degener 24:485–494. https://doi.org/10.1080/21678421.2023.2174881

    Article  PubMed  Google Scholar 

  100. Shellikeri S, Myers M, Black SE, Abrahao A, Zinman L, Yunusova Y (2019) Speech network regional involvement in bulbar ALS: a multimodal structural MRI study. Amyotroph Lateral Scler Frontotemporal Degener 20:385–395. https://doi.org/10.1080/21678421.2019.1612920

    Article  PubMed  PubMed Central  Google Scholar 

  101. Shinotoh H, Shimada H, Kokubo Y, Tagai K, Niwa F, Kitamura S, Endo H, Ono M, Kimura Y, Hirano S, Mimuro M, Ichise M, Sahara N, Zhang MR, Suhara T, Higuchi M (2019) Tau imaging detects distinctive distribution of tau pathology in ALS/PDC on the Kii Peninsula. Neurology 92:e136–e147. https://doi.org/10.1212/wnl.0000000000006736

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Smith MC (1960) Nerve fibre degeneration in the brain in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 23:269–282

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Soriani MH, Desnuelle C (2009) Epidemiology of amyotrophic lateral sclerosis. Revue neurologique 165:627–640. https://doi.org/10.1016/j.neurol.2009.04.004

    Article  PubMed  Google Scholar 

  104. Ta D, Ishaque A, Srivastava O, Hanstock C, Seres P, Eurich DT, Luk C, Briemberg H, Frayne R, Genge AL, Graham SJ, Korngut L, Zinman L, Kalra S (2021) Progressive neurochemical abnormalities in cognitive and motor subgroups of amyotrophic lateral sclerosis: a prospective multicenter study. Neurology 97:e803–e813. https://doi.org/10.1212/wnl.0000000000012367

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Tamaki Y, Ross JP, Alipour P, Castonguay C-É, Li B, Catoire H, Rochefort D, Urushitani M, Takahashi R, Sonnen JA, Stifani S, Dion PA, Rouleau GA (2023) Spinal cord extracts of amyotrophic lateral sclerosis spread TDP-43 pathology in cerebral organoids. PLoS Genet 19:e1010606. https://doi.org/10.1371/journal.pgen.1010606

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Tang Y, Liu P, Li W, Liu Z, Zhou M, Li J, Yuan Y, Fang L, Wang M, Shen L, Huang Y, Tang B, Wang J, Hu S (2022) Detection of changes in synaptic density in amyotrophic lateral sclerosis patients using (18) F-SynVesT-1 positron emission tomography. Eur J Neurol 29:2934–2943. https://doi.org/10.1111/ene.15451

    Article  PubMed  Google Scholar 

  107. Temp AGM, Dyrba M, Büttner C, Kasper E, Machts J, Kaufmann J, Vielhaber S, Teipel S, Prudlo J (2021) Cognitive profiles of amyotrophic lateral sclerosis differ in resting-state functional connectivity: an fMRI study. Front Neurosci 15:682100. https://doi.org/10.3389/fnins.2021.682100

    Article  PubMed  PubMed Central  Google Scholar 

  108. Thome J, Steinbach R, Grosskreutz J, Durstewitz D, Koppe G (2022) Classification of amyotrophic lateral sclerosis by brain volume, connectivity, and network dynamics. Hum Brain Mapp 43:681–699. https://doi.org/10.1002/hbm.25679

    Article  PubMed  Google Scholar 

  109. Tondo G, Iaccarino L, Cerami C, Vanoli GE, Presotto L, Masiello V, Coliva A, Salvi F, Bartolomei I, Mosca L, Lunetta C, Perani D (2020) (11) C-PK11195 PET-based molecular study of microglia activation in SOD1 amyotrophic lateral sclerosis. Ann Clin Transl Neurol 7:1513–1523. https://doi.org/10.1002/acn3.51112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Tondo G, Mazzini L, Caminiti SP, Sarnelli MF, Corrado L, Matheoud R, D’Alfonso S, Cantello R, Sacchetti GM, Perani D, Comi C, De Marchi F (2022) Clinical relevance of single-subject brain metabolism patterns in amyotrophic lateral sclerosis mutation carriers. NeuroImage Clinical 36:103222. https://doi.org/10.1016/j.nicl.2022.103222

    Article  PubMed  PubMed Central  Google Scholar 

  111. Trojsi F, Corbo D, Caiazzo G, Piccirillo G, Monsurrò MR, Cirillo S, Esposito F, Tedeschi G (2013) Motor and extramotor neurodegeneration in amyotrophic lateral sclerosis: a 3T high angular resolution diffusion imaging (HARDI) study. Amyotrophic Lateral Scler Frontotemporal Degener 14:553–561. https://doi.org/10.3109/21678421.2013.785569

    Article  Google Scholar 

  112. Trojsi F, Di Nardo F, Caiazzo G, Siciliano M, D’Alvano G, Ferrantino T, Passaniti C, Ricciardi D, Esposito S, Lavorgna L, Russo A, Bonavita S, Cirillo M, Santangelo G, Esposito F, Tedeschi G (2021) Hippocampal connectivity in amyotrophic lateral sclerosis (ALS): more than Papez circuit impairment. Brain Imaging Behav 15:2126–2138. https://doi.org/10.1007/s11682-020-00408-1

    Article  PubMed  Google Scholar 

  113. Trojsi F, Di Nardo F, Siciliano M, Caiazzo G, Femiano C, Passaniti C, Ricciardi D, Russo A, Bisecco A, Esposito S, Monsurrò MR, Cirillo M, Santangelo G, Esposito F, Tedeschi G (2021) Frontotemporal degeneration in amyotrophic lateral sclerosis (ALS): a longitudinal MRI one-year study. CNS Spectr 26:258–267. https://doi.org/10.1017/s109285292000005x

    Article  PubMed  Google Scholar 

  114. Trojsi F, Di Nardo F, Siciliano M, Caiazzo G, Passaniti C, D’Alvano G, Ricciardi D, Russo A, Bisecco A, Lavorgna L, Bonavita S, Cirillo M, Esposito F, Tedeschi G (2021) Resting state functional MRI brain signatures of fast disease progression in amyotrophic lateral sclerosis: a retrospective study. Amyotroph Lateral Scler Frontotemporal Degener 22:117–126. https://doi.org/10.1080/21678421.2020.1813306

    Article  PubMed  Google Scholar 

  115. Van Weehaeghe D, Babu S, De Vocht J, Zürcher NR, Chew S, Tseng CJ, Loggia ML, Koole M, Rezaei A, Schramm G, Van Damme P, Hooker JM, Van Laere K, Atassi N (2020) Moving toward multicenter therapeutic trials in amyotrophic lateral sclerosis: feasibility of data pooling using different translocator protein PET radioligands. J Nucl Med 61:1621–1627. https://doi.org/10.2967/jnumed.119.241059

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Van Weehaeghe D, Ceccarini J, Delva A, Robberecht W, Van Damme P, Van Laere K (2016) Prospective validation of 18F-FDG brain PET discriminant analysis methods in the diagnosis of amyotrophic lateral sclerosis. J Nucl Med 57:1238–1243. https://doi.org/10.2967/jnumed.115.166272

    Article  CAS  PubMed  Google Scholar 

  117. Van Weehaeghe D, Devrome M, Schramm G, De Vocht J, Deckers W, Baete K, Van Damme P, Koole M, Van Laere K (2020) Combined brain and spinal FDG PET allows differentiation between ALS and ALS mimics. Eur J Nucl Med Mol Imaging 47:2681–2690. https://doi.org/10.1007/s00259-020-04786-y

    Article  PubMed  Google Scholar 

  118. Wang C, Foxley S, Ansorge O, Bangerter-Christensen S, Chiew M, Leonte A, Menke RA, Mollink J, Pallebage-Gamarallage M, Turner MR, Miller KL, Tendler BC (2020) Methods for quantitative susceptibility and R2* mapping in whole post-mortem brains at 7T applied to amyotrophic lateral sclerosis. Neuroimage 222:117216. https://doi.org/10.1016/j.neuroimage.2020.117216

    Article  CAS  PubMed  Google Scholar 

  119. Wang D, Liang W, Huo D, Wang H, Wang Y, Cong C, Zhang C, Yan S, Gao M, Su X, Tan X, Zhang W, Han L, Zhang D, Feng H (2023) SPY1 inhibits neuronal ferroptosis in amyotrophic lateral sclerosis by reducing lipid peroxidation through regulation of GCH1 and TFR1. Cell Death Differ 30:369–382. https://doi.org/10.1038/s41418-022-01089-7

    Article  CAS  PubMed  Google Scholar 

  120. Wang T, Tomas D, Perera ND, Cuic B, Luikinga S, Viden A, Barton SK, McLean CA, Samson AL, Southon A, Bush AI, Murphy JM, Turner BJ (2022) Ferroptosis mediates selective motor neuron death in amyotrophic lateral sclerosis. Cell Death Differ 29:1187–1198. https://doi.org/10.1038/s41418-021-00910-z

    Article  CAS  PubMed  Google Scholar 

  121. Weerasekera A, Crabbé M, Tomé SO, Gsell W, Sima D, Casteels C, Dresselaers T, Deroose C, Van Huffel S, Rudolf Thal D, Van Damme P, Himmelreich U (2020) Non-invasive characterization of amyotrophic lateral sclerosis in a hTDP-43(A315T) mouse model: a PET-MR study. NeuroImage Clinical 27:102327. https://doi.org/10.1016/j.nicl.2020.102327

    Article  PubMed  PubMed Central  Google Scholar 

  122. Weerasekera A, Peeters R, Sima D, Dresselaers T, Sunaert S, De Vocht J, Claeys K, Van Huffel S, Van Damme P, Himmelreich U (2019) Motor cortex metabolite alterations in amyotrophic lateral sclerosis assessed in vivo using edited and non-edited magnetic resonance spectroscopy. Brain Res 1718:22–31. https://doi.org/10.1016/j.brainres.2019.04.018

    Article  CAS  PubMed  Google Scholar 

  123. Weerasekera A, Sima DM, Dresselaers T, Van Huffel S, Van Damme P, Himmelreich U (2018) Non-invasive assessment of disease progression and neuroprotective effects of dietary coconut oil supplementation in the ALS SOD1(G93A) mouse model: a (1)H-magnetic resonance spectroscopic study. NeuroImage Clinical 20:1092–1105. https://doi.org/10.1016/j.nicl.2018.09.011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Weidman EK, Schweitzer AD, Niogi SN, Brady EJ, Starikov A, Askin G, Shahbazi M, Wang Y, Lange D, Tsiouris AJ (2019) Diffusion tensor imaging and quantitative susceptibility mapping as diagnostic tools for motor neuron disorders. Clin Imaging 53:6–11. https://doi.org/10.1016/j.clinimag.2018.09.015

    Article  PubMed  Google Scholar 

  125. Welton T, Maller JJ, Lebel RM, Tan ET, Rowe DB, Grieve SM (2019) Diffusion kurtosis and quantitative susceptibility mapping MRI are sensitive to structural abnormalities in amyotrophic lateral sclerosis. NeuroImage Clin 24. https://doi.org/10.1016/j.nicl.2019.101953

  126. Yamashita T, Hatakeyama T, Sato K, Fukui Y, Hishikawa N, Ohta Y, Nishiyama Y, Kawai N, Tamiya T, Abe K (2017) Flow-metabolism uncoupling in the cervical spinal cord of ALS patients. Neurological Sci 38:659–665. https://doi.org/10.1007/s10072-017-2823-y

    Article  Google Scholar 

  127. Yu Z, Zhang H, Wang Y (2023) Cervical Spondylotic amyotrophy initially misdiagnosed as amyotrophic lateral sclerosis. World Neurosurg. https://doi.org/10.1016/j.wneu.2023.08.130

    Article  PubMed  Google Scholar 

  128. Zejlon C, Nakhostin D, Winklhofer S, Pangalu A, Kulcsar Z, Lewandowski S, Finnsson J, Piehl F, Ingre C, Granberg T, Ineichen BV (2022) Structural magnetic resonance imaging findings and histopathological correlations in motor neuron diseases-a systematic review and meta-analysis. Front Neurol 13:947347. https://doi.org/10.3389/fneur.2022.947347

    Article  PubMed  PubMed Central  Google Scholar 

  129. Zhang F, Chen G, He M, Dai J, Shang H, Gong Q, Jia Z (2018) Altered white matter microarchitecture in amyotrophic lateral sclerosis: a voxel-based meta-analysis of diffusion tensor imaging. NeuroImage Clinical 19:122–129. https://doi.org/10.1016/j.nicl.2018.04.005

    Article  PubMed  PubMed Central  Google Scholar 

  130. Zhang H, Schneider T, Wheeler-Kingshott CA, Alexander DC (2012) NODDI: practical in vivo neurite orientation dispersion and density imaging of the human brain. Neuroimage 61:1000–1016. https://doi.org/10.1016/j.neuroimage.2012.03.072

    Article  PubMed  Google Scholar 

  131. Zhou B, Wang H, Cai Y, Wen H, Wang L, Zhu M, Chen Y, Yu Y, Lu X, Zhou M, Fang P, Li X, Hong D (2020) FUS P525L mutation causing amyotrophic lateral sclerosis and movement disorders. Brain Behav 10:e01625. https://doi.org/10.1002/brb3.1625

    Article  PubMed  PubMed Central  Google Scholar 

  132. Zoccolella S, Mastronardi A, Scarafino A, Iliceto G, D’Errico E, Fraddosio A, Tempesta I, Morea A, Scaglione G, Introna A, Simone IL (2020) Motor-evoked potentials in amyotrophic lateral sclerosis: potential implications in detecting subclinical UMN involvement in lower motor neuron phenotype. J Neurol 267:3689–3695. https://doi.org/10.1007/s00415-020-10073-5

    Article  PubMed  PubMed Central  Google Scholar 

  133. Zürcher NR, Loggia ML, Lawson R, Chonde DB, Izquierdo-Garcia D, Yasek JE, Akeju O, Catana C, Rosen BR, Cudkowicz ME, Hooker JM, Atassi N (2015) Increased in vivo glial activation in patients with amyotrophic lateral sclerosis: assessed with [(11)C]-PBR28. NeuroImage Clin 7:409–414. https://doi.org/10.1016/j.nicl.2015.01.009

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This study was funded by the Medical and Health Talents Special Foundation of Jilin Province (No. JLSWSRCZX2023-13), Department of Science and Technology of Jilin Province, and the CSA Cerebrovascular Disease Innovation Medical Research Fund.

Author information

Authors and Affiliations

  1. Department of Neurology and Neuroscience Center, The First Hospital of Jilin University, Changchun, 130021, China

    Wei Sun, Xiao-Jing Wei, Hui Sun, Zhen-Wei Ma & Xue-Fan Yu

  2. Department of Mechanical Engineering, The University of Hong Kong, Pokfulam, Hong Kong SAR, China

    Si-Han Liu

Authors
  1. Wei Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Si-Han Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiao-Jing Wei
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hui Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zhen-Wei Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xue-Fan Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Manuscript writing: WS; manuscript revision: S-HL, X-JW, HS, and Z-WM; prepare figure: S-HL and WS; supervision: X-FY

Corresponding author

Correspondence to Xue-Fan Yu.

Ethics declarations

Financial or non-financial interests

The authors have no financial or non-financial interests to disclose.

Conflicts of interest

The authors declare that they have no competing interests.

Consent to participate

This manuscript does not contain clinical studies or patient data.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sun, W., Liu, SH., Wei, XJ. et al. Potential of neuroimaging as a biomarker in amyotrophic lateral sclerosis: from structure to metabolism. J Neurol 271, 2238–2257 (2024). https://doi.org/10.1007/s00415-024-12201-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-024-12201-x

Keywords

Search

Navigation