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European Radiology

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01-12-2018 | Neuro

Radial diffusivity as an imaging biomarker for early diagnosis of non-demented amyotrophic lateral sclerosis

Authors: Yifang Bao, Liqin Yang, Yan Chen, Biyun Zhang, Haiqing Li, Weijun Tang, Daoying Geng, Yuxin Li

Published in: European Radiology | Issue 12/2018

Abstract

Objectives

To explore the sensitivity of potential DTI-based biomarkers in detecting microstructural changes for whole-brain white matter in early stage amyotrophic lateral sclerosis (ALS), analyze the relationship between the DTI indices and disease status, and further clarify potential brain regions for disease monitoring and clinical assessment.

Methods

Thirty-three non-demented ALS patients and 32 age- and gender-matched subjects participated in this study. DTI data were acquired via 3.0T MRI scanner. Maps of diffusion-related indices including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were obtained. Tract-based spatial statistics (TBSS) were used to investigate whole-brain white matter changes of each index. Correlation analyses between both brain-wide and volume-of-interest (VOI)-wide white matter alterations and clinical factors including ALSFRS-R scores, disease duration, and progression rate were performed.

Results

Compared to healthy subjects, ALS patients showed significantly increased RD, MD and reduced FA, mainly along the corticospinal tract (CST) and the body of corpus callosum (CC). Increases in RD were broader than decreases in FA, in CST of both hemispheres. Meanwhile, involvement of several extra-motor regions was also revealed by RD. Significant positive correlation between ALSFRS-R scores and FA, negative correlation between ALSFRS-R and RD were found in left CST.

Conclusions

RD may be the most sensitive biomarker for the detection of early demyelination of white matter. Both RD and FA may serve as objective biomarkers for disease severity assessment. CST may be the most affected brain region in non-demented ALS.

Key Points

• Changes in RD were broader than those in FA in bilateral CST.

• Involvement of extra-motor regions was uncovered by RD.

• FA and RD in CST were related to ALSFRS-R scores.

van Es MA, Hardiman O, Chiò A et al (2017) Amyotrophic lateral sclerosis. Lancet 390:2084–2098CrossRef

Nzwalo H, de Abreu D, Swash M et al (2014) Delayed diagnosis in ALS: The problem continues. J Neurol Sci 343:173–175CrossRef

Huynh W, Simon NG, Grosskreutz J et al (2016) Assessment of the upper motor neuron in amyotrophic lateral sclerosis. Clin Neurophysiol 127:2643–2660CrossRef

Melhem ER (2017) MR Imaging Biomarkers in Amyotrophic Lateral Sclerosis. Acad Radiol 24:1185–1186CrossRef

Wang S, Melhem ER, Poptani H, Woo JH (2011) Neuroimaging in amyotrophic lateral sclerosis. Neurotherapeutics 8:63–71CrossRef

Eisen A, Kim S, Pant B (1992) Amyotrophic lateral sclerosis (ALS): a phylogenetic disease of the corticomotoneuron? Muscle Nerve 15:219–224CrossRef

Williamson TL, Cleveland DW (1999) Slowing of axonal transport is a very early event in the toxicity of ALS-linked SOD1 mutants to motor neurons. Nat Neurosci 2:50–56CrossRef

Geevasinga N, Menon P, Özdinler PH et al (2016) Pathophysiological and diagnostic implications of cortical dysfunction in ALS. Nat Rev Neurol 12:651–661CrossRef

Filippi M, Agosta F (2016) Does neuroinflammation sustain neurodegeneration in ALS? Neurology 87:2508–2509CrossRef

10.

Senda J, Atsuta N, Watanabe H et al (2017) Structural MRI correlates of amyotrophic lateral sclerosis progression. J Neurol Neurosurg Psychiatry 88:901–907CrossRef

11.

Ferraro PM, Agosta F, Riva N et al (2017) Multimodal structural MRI in the diagnosis of motor neuron diseases. Neuroimage Clin 16:240–247CrossRef

12.

Alshikho MJ, Zürcher NR, Loggia ML et al (2016) Glial activation colocalizes with structural abnormalities in amyotrophic lateral sclerosis. Neurology 87:2554–2561CrossRef

13.

Agosta F, Ferraro PM, Riva N et al (2016) Structural brain correlates of cognitive and behavioral impairment in MND. Hum Brain Mapp 37:1614–1626CrossRef

14.

Chiò A, Pagani M, Agosta F et al (2014) Neuroimaging in amyotrophic lateral sclerosis: insights into structural and functional changes. Lancet Neurol 13:1228–1240CrossRef

15.

Foerster BR, Welsh RC, Feldman EL (2013) 25 years of neuroimaging in amyotrophic lateral sclerosis. Nat Rev Neurol 9:513–524CrossRef

16.

Cirillo M, Esposito F, Tedeschi G et al (2012) Widespread Microstructural White Matter Involvement in Amyotrophic Lateral Sclerosis: A Whole-Brain DTI Study. AJNR Am J Neuroradiol 33:1102–1108CrossRef

17.

DSc PMCK, PhD SV, MBiostat BCC et al (2011) Amyotrophic lateral sclerosis. Lancet 377:942–955CrossRef

18.

Mitchell JD, Callagher P, Gardham J et al (2010) Timelines in the diagnostic evaluation of people with suspected amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND)--a 20-year review: can we do better? Amyotroph Lateral Scler 11:537–541CrossRef

19.

Menke RAL, Körner S, Filippini N et al (2014) Widespread grey matter pathology dominates the longitudinal cerebral MRI and clinical landscape of amyotrophic lateral sclerosis. Brain 137:2546–2555CrossRef

20.

Müller H-P, Turner MR, Grosskreutz J et al (2016) A large-scale multicentre cerebral diffusion tensor imaging study in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 87:570–579

21.

Keil C, Prell T, Peschel T et al (2012) Longitudinal diffusion tensor imaging in amyotrophic lateral sclerosis. BMC Neurosci 13:141CrossRef

22.

Martin AR, Aleksanderek I, Cohen-Adad J et al (2016) 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 10:192–238CrossRef

23.

Cardenas-Blanco A, Machts J, Acosta-Cabronero J et al (2016) Structural and diffusion imaging versus clinical assessment to monitor amyotrophic lateral sclerosis. Neuroimage Clin 11:408–414CrossRef

24.

Ellis CM, Simmons A, Jones DK et al (1999) Diffusion tensor MRI assesses corticospinal tract damage in ALS. Neurology 53:1051–1058CrossRef

25.

Prell T, Peschel T, Hartung V et al (2013) Diffusion tensor imaging patterns differ in bulbar and limb onset amyotrophic lateral sclerosis. Clin Neurol Neurosurg 115:1281–1287CrossRef

26.

Filippini N, Douaud G, Mackay CE et al (2010) Corpus callosum involvement is a consistent feature of amyotrophic lateral sclerosis. Neurology 75:1645–1652CrossRef

27.

Chapman MC, Jelsone-Swain L, Johnson TD et al (2014) Diffusion tensor MRI of the corpus callosum in amyotrophic lateral sclerosis. J Magn Reson Imaging 39:641–647CrossRef

28.

Brooks BR, Miller RG, Swash M et al (2000) El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord 1:293–299CrossRef

29.

Cedarbaum JM, Stambler N, Malta E et al (1999) The ALSFRS-R: a revised ALS functional rating scale that incorporates assessments of respiratory function. BDNF ALS Study Group (Phase III). J Neurol Sci 169:13–21CrossRef

30.

Smith SM, Jenkinson M, Johansen-Berg H et al (2006) Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data. Neuroimage 31:1487–1505CrossRef

31.

Nichols TE, Holmes AP (2002) Nonparametric permutation tests for functional neuroimaging: a primer with examples. Hum Brain Mapp 15:1–25CrossRef

32.

Smith SM, Nichols TE (2009) Threshold-free cluster enhancement: addressing problems of smoothing, threshold dependence and localisation in cluster inference. Neuroimage 44:83–98CrossRef

33.

Basser PJ, Jones DK (2002) Diffusion-tensor MRI: theory, experimental design and data analysis - a technical review. NMR Biomed 15:456–467CrossRef

34.

Basser PJ (1995) Inferring microstructural features and the physiological state of tissues from diffusion-weighted images. NMR Biomed 8:333–344CrossRef

35.

Basser PJ, Pajevic S, Pierpaoli C et al (2000) In vivo fiber tractography using DT-MRI data. Magn Reson Med 44:625–632CrossRef

36.

Song S-K, Sun S-W, Ramsbottom MJ et al (2002) Dysmyelination Revealed through MRI as Increased Radial (but Unchanged Axial) Diffusion of Water. Neuroimage 17:1429–1436CrossRef

37.

Song S-K, Yoshino J, Le TQ et al (2005) Demyelination increases radial diffusivity in corpus callosum of mouse brain. Neuroimage 26:132–140CrossRef

38.

Song S-K, Sun S-W, Ju W-K et al (2003) Diffusion tensor imaging detects and differentiates axon and myelin degeneration in mouse optic nerve after retinal ischemia. Neuroimage 20:1714–1722CrossRef

39.

Smith MC (1960) NERVE FIBRE DEGENERATION IN THE BRAIN IN AMYOTROPHIC LATERAL SCLEROSIS. J Neurol Neurosurg Psychiatry 23:269–282CrossRef

40.

Hayashi Y, Nagashima K, Urano Y, Iwata M (1986) Spinocerebellar degeneration with prominent involvement of the motor neuron system: autopsy report of a sporadic case. Acta Neuropathol 70:82–85CrossRef

41.

Taylor JP, Brown RH, Cleveland DW (2016) Decoding ALS: from genes to mechanism. Nature 539:197–206CrossRef

42.

Kang SH, Li Y, Fukaya M et al (2013) Degeneration and impaired regeneration of gray matter oligodendrocytes in amyotrophic lateral sclerosis. Nat Neurosci 16:571–579CrossRef

43.

Lee Y, Morrison BM, Li Y et al (2012) Oligodendroglia metabolically support axons and contribute to neurodegeneration. Nature 487:443–448CrossRef

44.

Metwalli NS, Benatar M, Nair G et al (2010) Utility of axial and radial diffusivity from diffusion tensor MRI as markers of neurodegeneration in amyotrophic lateral sclerosis. Brain Res 1348:156–164CrossRef

45.

Schuster C, Elamin M, Hardiman O, Bede P (2016) The segmental diffusivity profile of amyotrophic lateral sclerosis associated white matter degeneration. Eur J Neurol 23:1361–1371CrossRef

46.

Balendra R, Jones A, Jivraj N et al (2014) Estimating clinical stage of amyotrophic lateral sclerosis from the ALS Functional Rating Scale. Amyotroph Lateral Scler Frontotemporal Degener 15:279–284CrossRef

47.

Philips T, Rothstein JD (2014) Glial cells in amyotrophic lateral sclerosis. Exp Neurol 262:111–120CrossRef

48.

Coleman M (2005) Axon degeneration mechanisms: commonality amid diversity. Nat Rev Neurosci 6:889–898CrossRef

49.

Salvadores N, Sanhueza M, Manque P, Court FA (2017) Axonal Degeneration during Aging and Its Functional Role in Neurodegenerative Disorders. Front Neurosci 11:90–21CrossRef

50.

Sarica A, Cerasa A, Valentino P et al (2016) The corticospinal tract profile in amyotrophic lateral sclerosis. Hum Brain Mapp 38:727–739CrossRef

51.

Alruwaili AR, Pannek K, Coulthard A et al (2018) A combined tract-based spatial statistics and voxelbased morphometry study of the first MRI scan after diagnosis of amyotrophic lateral sclerosis with subgroup analysis. J Neuroradiol 45:41–48CrossRef

52.

Christidi F, Karavasilis E, Riederer F et al (2017) Gray matter and white matter changes in non-demented amyotrophic lateral sclerosis patients with or without cognitive impairment: A combined voxel-based morphometry and tract-based spatial statistics whole-brain analysis. Brain Imaging Behav 35:2639–2617

53.

Qiu D, Tan L-H, Zhou K, Khong P-L (2008) Diffusion tensor imaging of normal white matter maturation from late childhood to young adulthood: Voxel-wise evaluation of mean diffusivity, fractional anisotropy, radial and axial diffusivities, and correlation with reading development. Neuroimage 41:223–232CrossRef

54.

Imfeld A, Oechslin MS, Meyer M et al (2009) White matter plasticity in the corticospinal tract of musicians: A diffusion tensor imaging study. Neuroimage 46:600–607CrossRef

55.

Le Bihan D, Mangin JF, Poupon C et al (2001) Diffusion tensor imaging: concepts and applications. J Magn Reson Imaging 13:534–546CrossRef

56.

Basser PJ, Pierpaoli C (1996) Microstructural and physiological features of tissues elucidated by quantitative-diffusion-tensor MRI. J Magn Reson B 111:209–219CrossRef

57.

Vos SB, Jones DK, Jeurissen B et al (2012) The influence of complex white matter architecture on the mean diffusivity in diffusion tensor MRI of the human brain. Neuroimage 59:2208–2216CrossRef

58.

Tang YY, Lu Q, Fan M et al (2012) Mechanisms of white matter changes induced by meditation. Proc Natl Acad Sci U S A 109:10570–10574CrossRef

59.

Baldaranov D, Khomenko A, Kobor I et al (2017) Longitudinal Diffusion Tensor Imaging-Based Assessment of Tract Alterations: An Application to Amyotrophic Lateral Sclerosis. Front Hum Neurosci 11:567CrossRef

60.

Welniarz Q, Dusart I, Roze E (2017) The corticospinal tract: Evolution, development, and human disorders. Dev Neurobiol 77:810–829CrossRef

61.

Seo JP, Jang SH (2013) Different characteristics of the corticospinal tract according to the cerebral origin: DTI study. AJNR Am J Neuroradiol 34:1359–1363CrossRef

62.

Verstraete E, Polders DL, Mandl RCW et al (2014) Multimodal tract-based analysis in ALS patients at 7T: A specific white matter profile? Amyotroph Lateral Scler Frontotemporal Degener 15:84–92CrossRef

63.

Sach M (2004) Diffusion tensor MRI of early upper motor neuron involvement in amyotrophic lateral sclerosis. Brain 127:340–350CrossRef

64.

Sage CA, Van Hecke W, Peeters R et al (2009) Quantitative diffusion tensor imaging in amyotrophic lateral sclerosis: Revisited. Hum Brain Mapp 30:3657–3675CrossRef

65.

Cosottini M, Giannelli M, Siciliano G et al (2005) Diffusion-Tensor MR Imaging of Corticospinal Tract in Amyotrophic Lateral Sclerosis and Progressive Muscular Atrophy. Radiology 237:258–264CrossRef

66.

Kwan JY, Meoded A, Danielian LE et al (2012) Structural imaging differences and longitudinal changes in primary lateral sclerosis and amyotrophic lateral sclerosis. Neuroimage Clin 2:151–160CrossRef

67.

Bastin ME, Pettit LD, Bak TH et al (2013) Quantitative tractography and tract shape modeling in amyotrophic lateral sclerosis. J Magn Reson Imaging 38:1140–1145CrossRef

68.

Ciccarelli O, Behrens TE, Johansen-Berg H et al (2009) Investigation of white matter pathology in ALS and PLS using tract-based spatial statistics. Hum Brain Mapp 30:615–624CrossRef

69.

Iwata NK, Kwan JY, Danielian LE et al (2011) White matter alterations differ in primary lateral sclerosis and amyotrophic lateral sclerosis. Brain 134:2642–2655CrossRef

70.

Kasper E, Schuster C, Machts J et al (2014) Microstructural White Matter Changes Underlying Cognitive and Behavioural Impairment in ALS – An In Vivo Study Using DTI. PLoS One 9:e114543–e114519CrossRef

71.

Kilani M, Micallef J, Soubrouillard C et al (2004) A longitudinal study of the evolution of cognitive function and affective state in patients with amyotrophic lateral sclerosis. Amyotrophic Lateral Scler Other Motor Neuron Disord 5:46–54CrossRef

72.

Lee D-H, Lee D-W, Han B-S (2016) Symmetrical Location Characteristics of Corticospinal Tract Associated With Hand Movement in the Human Brain. Medicine (Baltimore) 95:e3317–e3316CrossRef

Title: Radial diffusivity as an imaging biomarker for early diagnosis of non-demented amyotrophic lateral sclerosis
Authors: Yifang Bao
Liqin Yang
Yan Chen
Biyun Zhang
Haiqing Li
Weijun Tang
Daoying Geng
Yuxin Li
Publication date: 01-12-2018
Publisher: Springer Berlin Heidelberg
Published in: European Radiology / Issue 12/2018
Print ISSN: 0938-7994
Electronic ISSN: 1432-1084
DOI: https://doi.org/10.1007/s00330-018-5506-z

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Radial diffusivity as an imaging biomarker for early diagnosis of non-demented amyotrophic lateral sclerosis

Abstract

Objectives

Methods

Results

Conclusions

Key Points

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Objectives

Methods

Results

Conclusions

Key Points

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