Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Diffusion Kurtosis Imaging as a Tool in Neurotoxicology

Abstract

This commentary serves as an introduction to the magnetic resonance imaging (MRI) technique called diffusion kurtosis imaging (DKI) employed in the study by Arab et al. in the present issue of Neurotoxicology Research. In their study, DKI is employed for longitudinal investigation of a methamphetamine intoxication model of Parkinson’s disease. The study employs an impressive number of animals and combines DKI with behavioral analysis at multiple time points. The commentary discusses some aspects of the study design especially the strength of combining behavioral analysis with MRI in an effort to provide as thorough a characterization and validity assessment of the animal model and cohort as possible. The potential clinical value of combining multiple MRI techniques (multimodal MRI) in PD is discussed as well as the benefit of multimodal MRI combined with behavioral analysis and subsequent histological analysis for in-depth characterization of animal models.

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

Fig. 1

References

  1. Arab, A., Ruda-Kucerova, J., Minsterova, A., Drazanova, E., Szabó, N., Starcuk Jr., Z., et al. (2019). Diffusion kurtosis imaging detects microstructural changes in a methamphetamineinduced mouse model of Parkinson’s disease Neurotox Res

  2. Bai Y, Lin Y, Tian J, Shi D, Cheng J, Haacke EM, Hong X, Ma B, Zhou J, Wang M (2016) Grading of gliomas by using monoexponential, biexponential, and stretched exponential diffusion-weighted MR imaging and diffusion kurtosis MR imaging. Radiology 278(2):496–504. https://doi.org/10.1148/radiol.2015142173

  3. Basser PJ (1995) Inferring microstructural features and the physiological state of tissues from diffusion-weighted images. NMR Biomed 8(7–8):333–344

  4. Basser PJ, Mattiello J, LeBihan D (1994a) Estimation of the effective self-diffusion tensor from the NMR spin echo. J Magn Reson B 103(3):247–254

  5. Basser PJ, Mattiello J, Lebihan D (1994b) MR diffusion tensor spectroscopy and imaging. Biophys J 66(1):259–267

  6. Bay V, Kjolby BF, Iversen NK, Mikkelsen IK, Ardalan M, Nyengaard JR et al (2018) Stroke infarct volume estimation in fixed tissue: comparison of diffusion kurtosis imaging to diffusion weighted imaging and histology in a rodent MCAO model. Plos One 13(4):e0196161. https://doi.org/10.1371/journal.pone.0196161

  7. Beaulieu C (2002) The basis of anisotropic water diffusion in the nervous system - a technical review. NMR Biomed 15(7–8):435–455. https://doi.org/10.1002/nbm.782

  8. Borghammer P, Knudsen K, Fedorova TD, Brooks DJ (2017) Imaging Parkinson’s disease below the neck. NPJ Parkinsons Dis 3:15. https://doi.org/10.1038/s41531-017-0017-1

  9. Braak H, Del Tredici K, Rub U, de Vos RAI, Steur ENHJ, Braak E (2003) Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging 24(2):197–211. https://doi.org/10.1016/S0197-4580(02)00065-9

  10. Chuhutin A, Hansen B, Jespersen SN (2017) Precision and accuracy of diffusion kurtosis estimation and the influence of b-value selection. NMR Biomed 30(11):e3777. https://doi.org/10.1002/nbm.3777

  11. Dagher, A., and Zeighami, Y. (2018). Testing the protein propagation hypothesis of Parkinson disease. J Exp Neurosci 12. https://doi.org/10.1177/1179069518786715

  12. Doucette J, Wei LX, Hernandez-Torres E, Kames C, Forkert ND, Aamand R et al (2019) Rapid solution of the Bloch-Torrey equation in anisotropic tissue: application to dynamic susceptibility contrast MRI of cerebral white matter. Neuroimage 185:198–207. https://doi.org/10.1016/j.neuroimage.2018.10.035

  13. Falangola MF, Jensen JH, Tabesh A, Hu C, Deardorff RL, Babb JS, Ferris S, Helpern JA (2013) Non-Gaussian diffusion MRI assessment of brain microstructure in mild cognitive impairment and Alzheimer’s disease. Magn Reson Imaging 31(6):840–846. https://doi.org/10.1016/j.mri.2013.02.008

  14. Fieremans E, Jensen JH, Helpern JA (2011) White matter characterization with diffusional kurtosis imaging. Neuroimage 58(1):177–188. https://doi.org/10.1016/j.neuroimage.2011.06.006

  15. Flint JJ, Hansen B, Fey M, Schmidig D, King MA, Vestergaard-Poulsen P, Blackband SJ (2010) Cellular-level diffusion tensor microscopy and fiber tracking in mammalian nervous tissue with direct histological correlation. Neuroimage 52(2):556–561. https://doi.org/10.1016/j.neuroimage.2010.04.031

  16. Flint JJ, Hansen B, Blackband SJ (2016) Diffusion tensor microscopy data (15.6 μm in-plane) of white matter tracts in the human, pig, and rat spinal cord with corresponding tissue histology. Data in Brief 9:271–274. https://doi.org/10.1016/j.dib.2016.08.020

  17. Garza-Villarreal et al (2017) The effect of crack cocaine addiction and age on the microstructure and morphology of the human striatum and thalamus using shape analysis and fast diffusion kurtosis imaging. Transl Psychiatry 7(5):e1122. https://doi.org/10.1038/tp.2017.92

  18. Granado, N., Ares-Santos, S., and Moratalla, R. (2013). Methamphetamine and Parkinson’s disease. Parkinsons Dis 308052. https://doi.org/10.1155/2013/308052

  19. Grossman EJ, Ge Y, Jensen JH, Babb JS, Miles L, Reaume J, Silver JM, Grossman RI, Inglese M (2012) Thalamus and cognitive impairment in mild traumatic brain injury: a diffusional kurtosis imaging study. J Neurotrauma 29(13):2318–2327. https://doi.org/10.1089/neu.2011.1763

  20. Grossman EJ, Jensen JH, Babb JS, Chen Q, Tabesh A, Fieremans E, Xia D, Inglese M, Grossman RI (2013) Cognitive impairment in mild traumatic brain injury: a longitudinal diffusional kurtosis and perfusion imaging study. AJNR Am J Neuroradiol 34(5):951–957, S951-953. https://doi.org/10.3174/ajnr.A3358

  21. Hansen B, Jespersen SN (2016a) Data for evaluation of fast kurtosis strategies, b-value optimization and exploration of diffusion MRI contrast. Sci Data 3. https://doi.org/10.1038/sdata.2016.72

  22. Hansen B, Jespersen SN (2016b) Kurtosis fractional anisotropy, its contrast and estimation by proxy. Sci Rep 6:23999. https://doi.org/10.1038/srep23999

  23. Hansen B, Jespersen SN (2017) Recent developments in fast kurtosis imaging. Front Phys 5:40. https://doi.org/10.3389/fphy.2017.00040

  24. Hansen B, Flint JJ, Heon-Lee C, Fey M, Vincent F, King MA, Vestergaard-Poulsen P, Blackband SJ (2011) Diffusion tensor microscopy in human nervous tissue with quantitative correlation based on direct histological comparison. Neuroimage 57(4):1458–1465. https://doi.org/10.1016/j.neuroimage.2011.04.052

  25. Hansen B, Lund TE, Sangill R, Jespersen SN (2013) Experimentally and computationally fast method for estimation of a mean kurtosis. Magn Reson Med 69(6):1754–1760. https://doi.org/10.1002/mrm.24743

  26. Hansen B, Lund TE, Sangill R, Jespersen SN (2014) Erratum: Hansen, Lund, Sangill, and Jespersen. Experimentally and computationally fast method for estimation of a mean kurtosis (Magnetic Resonance in Medicine (2013b) 69 (1754-1760)). Magn Reson Med 71(6):2250. https://doi.org/10.1002/mrm.25090

  27. Hansen B, Lund TE, Sangill R, Stubbe E, Finsterbusch J, Jespersen SN (2016) Experimental considerations for fast kurtosis imaging. Magn Reson Med 76(5):1455–1468. https://doi.org/10.1002/mrm.26055

  28. Hansen B, Khan AR, Shemesh N, Lund TE, Sangill R, Eskildsen SF, Østergaard L, Jespersen SN (2017) White matter biomarkers from fast protocols using axially symmetric diffusion kurtosis imaging. NMR Biomed 30(9):e3741. https://doi.org/10.1002/nbm.3741

  29. Hikishima K, Ando K, Yano R, Kawai K, Komaki Y, Inoue T, Itoh T, Yamada M, Momoshima S, Okano HJ, Okano H (2015) Parkinson disease: diffusion MR imaging to detect nigrostriatal pathway loss in a marmoset model treated with 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Radiology 275(2):430–437. https://doi.org/10.1148/radiol.14140601

  30. Hui ES, Fieremans E, Jensen JH, Tabesh A, Feng W, Bonilha L, Spampinato MV, Adams R, Helpern JA (2012) Stroke assessment with diffusional kurtosis imaging. Stroke 43(11):2968–2973. https://doi.org/10.1161/STROKEAHA.112.657742

  31. Inglese M, Bester M (2010) Diffusion imaging in multiple sclerosis: research and clinical implications. NMR Biomed 23(7):865–872. https://doi.org/10.1002/nbm.1515

  32. Jensen JH, Helpern JA (2010) MRI quantification of non-Gaussian water diffusion by kurtosis analysis. NMR Biomed 23(7):698–710. https://doi.org/10.1002/nbm.1518

  33. Jensen JH, Helpern JA, Ramani A, Lu H, Kaczynski K (2005) Diffusional kurtosis imaging: the quantification of non-gaussian water diffusion by means of magnetic resonance imaging. Magn Reson Med 53(6):1432–1440. https://doi.org/10.1002/mrm.20508

  34. Kamagata K, Zalesky A, Hatano T, Ueda R, Di Biase MA, Okuzumi A et al (2017) Gray matter abnormalities in idiopathic Parkinson’s disease: evaluation by diffusional kurtosis imaging and neurite orientation dispersion and density imaging. Hum Brain Mapp 38(7):3704–3722. https://doi.org/10.1002/hbm.23628

  35. Khairnar A, Latta P, Drazanova E, Ruda-Kucerova J, Szabo N, Arab A et al (2015) Diffusion kurtosis imaging detects microstructural alterations in brain of alpha-Synuclein overexpressing transgenic mouse model of Parkinson’s disease: a pilot study. Neurotox Res 28(4):281–289. https://doi.org/10.1007/s12640-015-9537-9

  36. Khairnar A, Ruda-Kucerova J, Drazanova E, Szabo N, Latta P, Arab A et al (2016) Late-stage alpha-synuclein accumulation in TNWT-61 mouse model of Parkinson’s disease detected by diffusion kurtosis imaging. J Neurochem 136(6):1259–1269. https://doi.org/10.1111/jnc.13500

  37. Khairnar A, Ruda-Kucerova J, Szabo N, Drazanova E, Arab A, Hutter-Paier B et al (2017) Early and progressive microstructural brain changes in mice overexpressing human alpha-synuclein detected by diffusion kurtosis imaging. Brain Behav Immun 61:197–208. https://doi.org/10.1016/j.bbi.2016.11.027

  38. Khan AR, Chuhutin A, Wiborg O, Kroenke CD, Nyengaard JR, Hansen B, Jespersen SN (2016a) Biophysical modeling of high field diffusion MRI demonstrates microstructural aberration in chronic mild stress rat brain. Neuroimage 142:421–430

  39. Khan AR, Chuhutin A, Wiborg O, Kroenke CD, Nyengaard JR, Hansen B, Jespersen SN (2016b) Summary of high field diffusion MRI and microscopy data demonstrate microstructural aberration in chronic mild stress rat brain. Data Brief 8:934–937. https://doi.org/10.1016/j.dib.2016.06.061

  40. Khan AR, Hansen B, Iversen NK, Olesen JL, Perez MA, Kuhn DM, et al (2019) Longitudinal, multiparametric MRI assessment of repetitive mild TBI in rats. Preprint, https://www.biorxiv.org/content/biorxiv/early/2019/06/10/666024.full.pdf

  41. Kjolby BF, Khan AR, Chuhutin A, Pedersen L, Jensen JB, Jakobsen S et al (2016) Fast diffusion kurtosis imaging of fibrotic mouse kidneys. NMR Biomed 29(12):1709–1719. https://doi.org/10.1002/nbm.3623

  42. Mazuel L, Chassain C, Jean B, Pereira B, Cladiere A, Speziale C et al (2016) Proton MR spectroscopy for diagnosis and evaluation of treatment efficacy in Parkinson disease. Radiology 278(2):505–513. https://doi.org/10.1148/radiol.2015142764

  43. Moratalla R, Khairnar A, Simola N, Granado N, Garcia-Montes JR, Porceddu PF et al (2017) Amphetamine-related drugs neurotoxicity in humans and in experimental animals: main mechanisms. Prog Neurobiol 155:149–170. https://doi.org/10.1016/j.pneurobio.2015.09.011

  44. Næss-Schmidt E, Blicher JU, Tietze A, Rask CU, Svendsen SW, Schröder A, et al (2017a) A cross-sectional diffusion MRI study in patients with extensive post-concussion symptoms 2–5 months after mild traumatic brain injury. In review

  45. Næss-Schmidt ET, Blicher JU, Eskildsen SF, Tietze A, Hansen B, Stubbs PW, Jespersen S, Østergaard L, Nielsen JF (2017b) Microstructural changes in the thalamus after mild traumatic brain injury: a longitudinal diffusion and mean kurtosis tensor MRI study. Brain Inj 31(2):230–236. https://doi.org/10.1080/02699052.2016.1229034

  46. Ostergaard L, Engedal TS, Aamand R, Mikkelsen R, Iversen NK, Anzabi M et al (2014) Capillary transit time heterogeneity and flow-metabolism coupling after traumatic brain injury. J Cereb Blood Flow Metab 34(10):1585–1598. https://doi.org/10.1038/jcbfm.2014.131

  47. Poot DH, den Dekker AJ, Achten E, Verhoye M, Sijbers J (2010) Optimal experimental design for diffusion kurtosis imaging. IEEE Trans Med Imaging 29(3):819–829. https://doi.org/10.1109/TMI.2009.2037915

  48. Rosenkrantz AB, Padhani AR, Chenevert TL, Koh DM, De Keyzer F, Taouli B et al (2015) Body diffusion kurtosis imaging: basic principles, applications, and considerations for clinical practice. J Magn Reson Imaging 42(5):1190–1202. https://doi.org/10.1002/jmri.24985

  49. Schocke MFH, Seppi K, Esterhammer R, Kremser C, Jaschke W, Poewe W et al (2002) Diffusion-weighted MRI differentiates the Parkinson variant of multiple system atrophy from PD. Neurology 58(4):575–580. https://doi.org/10.1212/Wnl.58.4.575

  50. Smith SM, Jenkinson M, Johansen-Berg H, Rueckert D, Nichols TE, Mackay CE, Watkins KE, Ciccarelli O, Cader MZ, Matthews PM, Behrens TEJ (2006) Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data. Neuroimage 31(4):1487–1505. https://doi.org/10.1016/j.neuroimage.2006.02.024

  51. Stoessl AJ (2015) Imaging in Parkinson’s disease: time to look below the neck. Brain 138:512–514. https://doi.org/10.1093/brain/awu392

  52. Surova Y, Nilsson M, Lampinen B, Latt J, Hall S, Widner H et al (2018) Alteration of putaminal fractional anisotropy in Parkinson’s disease: a longitudinal diffusion kurtosis imaging study. Neuroradiology 60(3):247–254. https://doi.org/10.1007/s00234-017-1971-3

  53. Tabesh A, Jensen JH, Ardekani BA, Helpern JA (2011) Estimation of tensors and tensor-derived measures in diffusional kurtosis imaging. Magn Reson Med 65(3):823–836. https://doi.org/10.1002/mrm.22655

  54. Tietze A, Hansen MB, Ostergaard L, Jespersen SN, Sangill R, Lund TE et al (2015) Mean diffusional kurtosis in patients with glioma: initial results with a fast imaging method in a clinical setting. Am J Neuroradiol 36(8):1472–1478. https://doi.org/10.3174/ajnr.A4311

  55. Van Cauter S, Veraart J, Sijbers J, Peeters RR, Himmelreich U, De Keyzer F et al (2012) Gliomas: diffusion kurtosis MR imaging in grading. Radiology 263(2):492–501. https://doi.org/10.1148/radiol.12110927

  56. Veraart J, Poot DHJ, Van Hecke W, Blockx I, Van der Linden A, Verhoye M et al (2011) More accurate estimation of diffusion tensor parameters using diffusion kurtosis imaging. Magn Reson Med 65(1):138–145. https://doi.org/10.1002/mrm.22603

  57. Wang JJ, Lin WY, Lu CS, Weng YH, Ng SH, Wang CH, Liu HL, Hsieh RH, Wan YL, Wai YY (2011) Parkinson disease: diagnostic utility of diffusion kurtosis imaging. Radiology 261(1):210–217. https://doi.org/10.1148/radiol.11102277

  58. Wang ML, Yu MM, Yang DX, Liu YL, Wei XE, Li WB (2018) Longitudinal microstructural changes in traumatic brain injury in rats: a diffusional kurtosis imaging, histology, and behavior study. Am J Neuroradiol 39(9):1650–1656. https://doi.org/10.3174/ajnr.A5737

  59. Weber RA, Hui ES, Jensen JH, Nie X, Falangola MF, Helpern JA, Adkins DAL (2015) Diffusional kurtosis and diffusion tensor imaging reveal different time-sensitive stroke-induced microstructural changes. Stroke 46(2):545–550. https://doi.org/10.1161/STROKEAHA.114.006782

  60. Westfall PH (2014) Kurtosis as Peakedness, 1905-2014. RIP Am Stat 68(3):191–195. https://doi.org/10.1080/00031305.2014.917055

  61. Yoshikawa K, Nakata Y, Yamada K, Nakagawa M (2004) Early pathological changes in the parkinsonian brain demonstrated by diffusion tensor MRI. J Neurol Neurosurg Psychiatry 75(3):481–484. https://doi.org/10.1136/jnnp.2003.021873

  62. Zhang G, Zhang Y, Zhang C, Wang Y, Ma G, Nie K, Xie H, Liu J, Wang L (2015) Diffusion kurtosis imaging of substantia nigra is a sensitive method for early diagnosis and disease evaluation in Parkinson’s disease. Parkinsons Dis 2015:207624–207625. https://doi.org/10.1155/2015/207624

  63. Zhang G, Zhang Y, Zhang C, Wang Y, Ma G, Nie K, Xie H, Liu J, Wang L (2016) Striatal silent lacunar infarction is associated with changes to the substantia nigra in patients with early-stage Parkinson’s disease: a diffusion kurtosis imaging study. J Clin Neurosci 33:138–141. https://doi.org/10.1016/j.jocn.2016.03.032

Download references

Author information

Correspondence to Brian Hansen.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Hansen, B. Diffusion Kurtosis Imaging as a Tool in Neurotoxicology. Neurotox Res 37, 41–47 (2020). https://doi.org/10.1007/s12640-019-00100-3

Download citation

Keywords

  • Preclinical MRI
  • Diffusion kurtosis
  • Parkinson’s disease
  • Animal models
  • Multimodal MRI