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Magnetic Resonance Materials in Physics, Biology and Medicine

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15.02.2019 | Research Article

Detection of axonal degeneration in a mouse model of Huntington’s disease: comparison between diffusion tensor imaging and anomalous diffusion metrics

verfasst von: Rodolfo G. Gatto, Allen Q. Ye, Luis Colon-Perez, Thomas H. Mareci, Anna Lysakowski, Steven D. Price, Scott T. Brady, Muge Karaman, Gerardo Morfini, Richard L. Magin

Erschienen in: Magnetic Resonance Materials in Physics, Biology and Medicine | Ausgabe 4/2019

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Abstract

Objective

The goal of this work is to study the changes in white matter integrity in R6/2, a well-established animal model of Huntington’s disease (HD) that are captured by ex vivo diffusion imaging (DTI) using a high field MRI (17.6 T).

Materials and methods

DTI and continuous time random walk (CTRW) models were used to fit changes in the diffusion-weighted signal intensity in the corpus callosum of controls and in R6/2 mice.

Results

A significant 13% decrease in fractional anisotropy, a 7% increase in axial diffusion, and a 33% increase in radial diffusion were observed between R6/2 and control mice. No change was observed in the CTRW beta parameter, but a significant decrease in the alpha parameter (− 21%) was measured. Histological analysis of the corpus callosum showed a decrease in axonal organization, myelin alterations, and astrogliosis. Electron microscopy studies demonstrated ultrastructural changes in degenerating axons, such as an increase in tortuosity in the R6/2 mice.

Conclusions

DTI and CTRW diffusion models display quantitative changes associated with the microstructural alterations observed in the corpus callosum of the R6/2 mice. The observed increase in the diffusivity and decrease in the alpha CTRW parameter providing support for the use of these diffusion models for non-invasive detection of white matter alterations in HD.

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Harper PS (1992) The epidemiology of Huntington’s disease. Hum Genet 89(4):365–376PubMedCrossRef

Pringsheim T, Wiltshire K, Day L, Dykeman J, Steeves T, Jette N (2012) The incidence and prevalence of Huntington’s disease: a systematic review and meta-analysis. Mov Disord 27(9):1083–1091PubMedCrossRef

Walker FO (2007) Huntington’s disease. Lancet 369(9557):218–228CrossRefPubMed

Han I, You Y, Kordower JH, Brady ST, Morfini GA (2010) Differential vulnerability of neurons in Huntington’s disease: the role of cell type-specific features. J Neurochem 113(5):1073–1091PubMedPubMedCentral

Perez-Navarro E, Canals JM, Gines S, Alberch J (2006) Cellular and molecular mechanisms involved in the selective vulnerability of striatal projection neurons in Huntington’s disease. Histol Histopathol 21(11):1217–1232PubMed

Pouladi MA, Morton AJ, Hayden MR (2013) Choosing an animal model for the study of Huntington’s disease. Nat Rev Neurosci 14(10):708–721PubMedCrossRef

Mangiarini L, Sathasivam K, Seller M, Cozens B, Harper A, Hetherington C, Lawton M, Trottier Y, Lehrach H, Davies SW, Bates GP (1996) Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice. Cell 87(3):493–506PubMedCrossRef

Menalled L, El-Khodor BF, Patry M, Suarez-Farinas M, Orenstein SJ, Zahasky B, Leahy C, Wheeler V, Yang XW, MacDonald M, Morton AJ, Bates G, Leeds J, Park L, Howland D, Signer E, Tobin A, Brunner D (2009) Systematic behavioral evaluation of Huntington’s disease transgenic and knock-in mouse models. Neurobiol Dis 35(3):319–336PubMedPubMedCentralCrossRef

Ramaswamy S, McBride JL, Kordower JH (2007) Animal models of Huntington’s disease. ILAR J 48(4):356–373PubMedCrossRef

10.

Gatto RG, Chu Y, Ye AQ, Price SD, Tavassoli E, Buenaventura A, Brady ST, Magin RL, Kordower JH, Morfini GA (2015) Analysis of YFP(J16)-R6/2 reporter mice and postmortem brains reveals early pathology and increased vulnerability of callosal axons in Huntington’s disease. Hum Mol Genet 24(18):5285–5298PubMedPubMedCentralCrossRef

11.

Rosas HD, Lee SY, Bender AC, Zaleta AK, Vangel M, Yu P, Fischl B, Pappu V, Onorato C, Cha JH, Salat DH, Hersch SM (2010) Altered white matter microstructure in the corpus callosum in Huntington’s disease: implications for cortical “disconnection”. NeuroImage 49(4):2995–3004PubMedCrossRef

12.

Poudel GR, Stout JC, Dominguez DJ, Churchyard A, Chua P, Egan GF, Georgiou-Karistianis N (2015) Longitudinal change in white matter microstructure in Huntington’s disease: the IMAGE-HD study. Neurobiol Dis 74:406–412PubMedCrossRef

13.

Poudel GR, Stout JC, Dominguez DJ, Salmon L, Churchyard A, Chua P, Georgiou-Karistianis N, Egan GF (2014) White matter connectivity reflects clinical and cognitive status in Huntington’s disease. Neurobiol Dis 65:180–187PubMedCrossRef

14.

Rosas HD, Tuch DS, Hevelone ND, Zaleta AK, Vangel M, Hersch SM, Salat DH (2006) Diffusion tensor imaging in presymptomatic and early Huntington’s disease: selective white matter pathology and its relationship to clinical measures. Mov Disord 21(9):1317–1325PubMedCrossRef

15.

Le Bihan D (2013) Apparent diffusion coefficient and beyond: what diffusion MR imaging can tell us about tissue structure. Radiology 268(2):318–322PubMedCrossRef

16.

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):823–836PubMedCrossRef

17.

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(4):1000–1016PubMedCrossRef

18.

Ingo C, Magin RL, Colon-Perez L, Triplett W, Mareci TH (2014) On random walks and entropy in diffusion-weighted magnetic resonance imaging studies of neural tissue. Magn Reson Med 71(2):617–627PubMedPubMedCentralCrossRef

19.

Yu Q, Reutens D, O’Brien K, Vegh V (2016) Tissue microstructure features derived from anomalous diffusion measurements in magnetic resonance imaging. Hum Brain Mapp 38(2):1068–1081PubMedCrossRef

20.

Karaman MM, Sui Y, Wang H, Magin RL, Li Y, Zhou XJ (2016) Differentiating low- and high-grade pediatric brain tumors using a continuous-time random-walk diffusion model at high b-values. Magn Reson Med 76(4):1149–1157PubMedCrossRef

21.

Xu B, Su L, Wang Z, Fan Y, Gong G, Zhu W, Gao P, Gao JH (2017) Anomalous diffusion in cerebral glioma assessed using a fractional motion model. Magn Reson Med 78(5):1944–1949PubMedCrossRef

22.

Karaman MM, Wang H, Sui Y, Engelhard HH, Li Y, Zhou XJ (2016) A fractional motion diffusion model for grading pediatric brain tumors. NeuroImage Clinical 12:707–714PubMedPubMedCentralCrossRef

23.

Gatto RG, Li W, Magin RL (2018) Diffusion tensor imaging identifies presymptomatic axonal degeneration in the spinal cord of ALS mice. Brain Res 1679:7CrossRef

24.

Alexander AL, Lee JE, Lazar M, Field AS (2007) Diffusion tensor imaging of the brain. Neurotherapeutics 4(3):316–329PubMedPubMedCentralCrossRef

25.

Gatto RG (2018) Diffusion tensor imaging as a tool to detect presymptomatic axonal degeneration in a preclinical spinal cord model of amyotrophic lateral sclerosis. Neural Regen Res 13(3):425–426PubMedPubMedCentralCrossRef

26.

Metzler R, Klafter J (2000) The random walk’s guide to anomalous diffusion: a fractional dynamics approach. Phys Rep 339:1–77CrossRef

27.

Magin RL, Ingo C, Colon-Perez L, Triplett W, Mareci TH (2013) Characterization of anomalous diffusion in porous biological tissues using fractional order derivatives and entropy. Microporous Mesoporous Mater 178:39–43PubMedPubMedCentralCrossRef

28.

Klages R, Radons G, Sokolov IM (eds) (2012) Anomalous transport: foundations and applications. Wiley, Weinheim

29.

Magin RL, Abdullah O, Baleanu D, Zhou XJ (2008) Anomalous diffusion expressed through fractional order differential operators in the Bloch–Torrey equation. J Magnetic Resonance 190(2):255–270CrossRef

30.

Gorenflo RMF, Moretti D, Pagnini G, Paradisi P (2002) Fractional diffusion: probability distributions and random walk models. Phys A 305(1–2):106–112CrossRef

31.

Wen CSH, Zhanga X, Korosak D (2010) Anomalous diffusion modeling by fractal and fractional derivatives. Comput Math Appl 59(5):1754–1758CrossRef

32.

Lenzi EK, Ribeiro HV, Tateishi AA, Zola RS, Evangelista LR (2016) Anomalous diffusion and transport in heterogeneous systems separated by a membrane. Proc Math Phys Eng Sci 472(2195):20160502PubMedPubMedCentralCrossRef

33.

Klafter J, Lim SC, Metzler R (eds) (2011) Fractional dynamics: recent advances. World Scientific, Sinapore

34.

Mainardi F (2000) Fractional calculus and waves in linear viscoelasticity: an introduction to mathematical models. Imperial College Press, London

35.

Ingo C, Magin RL, Parrish TB (2014) New insights into the fractional order diffusion equation using entropy and kurtosis. Entropy 16(11):5838–5852PubMedCrossRef

36.

Ingo C, Barrick TR, Webb AG, Ronen I (2017) Accurate Padé global approximations for the Mittag–Leffler function, its inverse, and its partial derivatives to efficiently compute convergent power series. Int J Appl Comput Mat 3:347–362CrossRef

37.

Mount SL, Schwarz JE, Taatjes DJ (1997) Prolonged storage of fixative for electron microscopy: effects on tissue preservation for diagnostic specimens. Ultrastruct Pathol 21(2):195–200PubMedCrossRef

38.

Karnovsky MJ (1965) A formaldehyde-glutaraldehyde fixative of high osmolality for use in electron microscopy. J Cell Biol 27:137A–138A

39.

Vranceanu F, Perkins GA, Terada M, Chidavaenzi RL, Ellisman MH, Lysakowski A (2012) Striated organelle, a cytoskeletal structure positioned to modulate hair-cell transduction. Proc Natl Acad Sci USA 109(12):4473–4478PubMedCrossRef

40.

Shaffer JJ, Ghayoor A, Long JD, Kim RE, Lourens S, O’Donnell LJ, Westin CF, Rathi Y, Magnotta V, Paulsen JS, Johnson HJ (2017) Longitudinal diffusion changes in prodromal and early HD: evidence of white-matter tract deterioration. Hum Brain Mapp 38(3):1460–1477PubMedPubMedCentralCrossRef

41.

Phillips O, Squitieri F, Sanchez-Castaneda C, Elifani F, Caltagirone C, Sabatini U, Di Paola M (2014) Deep white matter in Huntington’s disease. PLoS One 9(10):e109676PubMedPubMedCentralCrossRef

42.

Phillips OR, Joshi SH, Squitieri F, Sanchez-Castaneda C, Narr K, Shattuck DW, Caltagirone C, Sabatini U, DiPaola M (2016) Major superficial white matter abnormalities in Huntington’s disease. Front Neurosci 10:197PubMedPubMedCentralCrossRef

43.

Symms M, Jager HR, Schmierer K, Yousry TA (2004) A review of structural magnetic resonance neuroimaging. J Neurol Neurosurg Psychiat 75(9):1235–1244PubMedCrossRef

44.

Höfling F, Franosch T (2013) Anomalous transport in the crowded world of biological cells. Rep Prog Phys 76:046602PubMedCrossRef

45.

Schumer R, Meerschaert MM, Baeumer B (2009) Fractional advection–dispersion equations for modeling transport at the Earth surface. J Geophys Res 114:F00A07

46.

Morton AJ, Glynn D, Leavens W, Zheng Z, Faull RL, Skepper JN, Wight JM (2009) Paradoxical delay in the onset of disease caused by super-long CAG repeat expansions in R6/2 mice. Neurobiol Dis 33(3):331–341PubMedCrossRef

47.

Li H, Li SH, Yu ZX, Shelbourne P, Li XJ (2001) Huntingtin aggregate-associated axonal degeneration is an early pathological event in Huntington’s disease mice. J Neurosci 21(21):8473–8481PubMedPubMedCentralCrossRef

48.

Liu W, Yang J, Burgunder J, Cheng B, Shang H (2016) Diffusion imaging studies of Huntington’s disease: a meta-analysis. Park Relat Disord 32:94–101CrossRef

49.

Matsui JT, Vaidya JG, Johnson HJ, Magnotta VA, Long JD, Mills JA, Lowe MJ, Sakaie KE, Rao SM, Smith MM, Paulsen JS (2014) Diffusion weighted imaging of prefrontal cortex in prodromal Huntington’s disease. Hum Brain Mapp 35(4):1562–1573PubMedCrossRef

51.

Van Camp N, Blockx I, Camon L, de Vera N, Verhoye M, Veraart J, Van Hecke W, Martinez E, Soria G, Sijbers J, Planas AM, Van der Linden A (2012) A complementary diffusion tensor imaging (DTI)-histological study in a model of Huntington’s disease. Neurobiol Aging 33(5):945–959PubMedCrossRef

51.

Phillips O, Sanchez-Castaneda C, Elifani F, Maglione V, Di Pardo A, Caltagirone C, Squitieri F, Sabatini U, Di Paola M (2013) Tractography of the corpus callosum in Huntington’s disease. PLoS One 8(9):e73280PubMedPubMedCentralCrossRef

52.

Mori S, Crain BJ, Chacko VP, van Zijl PC (1999) Three-dimensional tracking of axonal projections in the brain by magnetic resonance imaging. Ann Neurol 45(2):265–269PubMedCrossRef

53.

Weaver KE, Richards TL, Liang O, Laurino MY, Samii A, Aylward EH (2009) Longitudinal diffusion tensor imaging in Huntington’s Disease. Exp Neurol 216(2):525–529PubMedCrossRef

54.

Porrero C, Rubio-Garrido P, Avendano C, Clasca F (2010) Mapping of fluorescent protein-expressing neurons and axon pathways in adult and developing Thy1-eYFP-H transgenic mice. Brain Res 1345:59–72PubMedCrossRef

55.

Chan CS, Surmeier DJ (2014) Astrocytes go awry in Huntington’s disease. Nat Neurosci 17(5):641–642PubMedCrossRef

56.

Huang B, Wei W, Wang G, Gaertig MA, Feng Y, Wang W, Li XJ, Li S (2015) Mutant huntingtin downregulates myelin regulatory factor-mediated myelin gene expression and affects mature oligodendrocytes. Neuron 85(6):1212–1226PubMedPubMedCentralCrossRef

57.

Bartzokis G, Lu PH, Tishler TA, Fong SM, Oluwadara B, Finn JP, Huang D, Bordelon Y, Mintz J, Perlman S (2007) Myelin breakdown and iron changes in Huntington’s disease: pathogenesis and treatment implications. Neurochem Res 32(10):1655–1664PubMedCrossRef

58.

Crawford HE, Hobbs NZ, Keogh R, Langbehn DR, Frost C, Johnson H, Landwehrmeyer B, Reilmann R, Craufurd D, Stout JC, Durr A, Leavitt BR, Roos RA, Tabrizi SJ, Scahill RI (2013) Corpus callosal atrophy in premanifest and early Huntington’s disease. J Huntingt Dis 2(4):517–526

59.

Gomez-Tortosa E, MacDonald ME, Friend JC, Taylor SA, Weiler LJ, Cupples LA, Srinidhi J, Gusella JF, Bird ED, Vonsattel JP, Myers RH (2001) Quantitative neuropathological changes in presymptomatic Huntington’s disease. Ann Neurol 49(1):29–34PubMedCrossRef

60.

Chilla GS, Tan CH, Xu C, Poh CL (2015) Diffusion weighted magnetic resonance imaging and its recent trend-a survey. Quant Imag Med Surg 5(3):407–422

61.

Zhang J, Jones MV, McMahon MT, Mori S, Calabresi PA (2012) In vivo and ex vivo diffusion tensor imaging of cuprizone-induced demyelination in the mouse corpus callosum. Magn Reson Med 67:750–759PubMedCrossRef

62.

Ryutaro Y, Junichi H, Yoshifumi A, Fumiko S, Keitaro Y, Yuji K, Hideyuki O, Kenji FT (2018) Quantitative temporal changes in DTI values coupled with histological properties in cuprizone-induced demyelination and remyelination. Neurochem Intern 119:151–158CrossRef

63.

Liang Y, Ye AQ, Chen W, Gatto RG, Colon-Perez L, Mareci TH, Magin RL (2016) A fractal derivative model for the characterization of anomalous diffusion in magnetic resonance imaging. Commun Nonlinear Sci Numer Simul 39:529–537CrossRef

64.

Ingo C, Sui Y, Chen Y, Parrish TB, Webb AG, Ronen I (2015) Parsimonious continuous time random walk models and kurtosis for diffusion in magnetic resonance of biological tissue. Front Phys 3:11PubMedPubMedCentralCrossRef

65.

Hrabe J, Hrabetova S, Segeth K (2004) A model of effective diffusion and tortuosity in the extracellular space of the brain. Biophys J 87(3):1606–1617PubMedPubMedCentralCrossRef

66.

Sui Y, Wang H, Liu G, Damen FW, Wanamaker C, Li Y, Zhou XJ (2015) Differentiation of low- and high-grade pediatric brain tumors with high b-value diffusion-weighted MR imaging and a fractional order calculus model. Radiology 277(2):489–496PubMedPubMedCentralCrossRef

Titel: Detection of axonal degeneration in a mouse model of Huntington’s disease: comparison between diffusion tensor imaging and anomalous diffusion metrics
verfasst von: Rodolfo G. Gatto
Allen Q. Ye
Luis Colon-Perez
Thomas H. Mareci
Anna Lysakowski
Steven D. Price
Scott T. Brady
Muge Karaman
Gerardo Morfini
Richard L. Magin
Publikationsdatum: 15.02.2019
Verlag: Springer International Publishing
Erschienen in: Magnetic Resonance Materials in Physics, Biology and Medicine / Ausgabe 4/2019
Print ISSN: 0968-5243
Elektronische ISSN: 1352-8661
DOI: https://doi.org/10.1007/s10334-019-00742-6

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Detection of axonal degeneration in a mouse model of Huntington’s disease: comparison between diffusion tensor imaging and anomalous diffusion metrics

Abstract

Objective

Materials and methods

Results

Conclusions

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Abstract

Objective

Materials and methods

Results

Conclusions

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