Skip to main content
SpringerLink
Log in

Diffusion tensor imaging of hippocampal network plasticity

  • Original Article
  • Published:
Brain Structure and Function Aims and scope Submit manuscript

Abstract

Diffusion tensor imaging (DTI) has become a valuable tool to investigate white matter integrity in the brain. DTI also gives contrast in gray matter, which has been relatively little explored in studies assessing post-injury structural abnormalities. The present study was designed to compare white and gray matter reorganization in the rat hippocampus after two epileptogenic brain injuries, status epilepticus (SE) and traumatic brain injury (TBI), using ex vivo high-resolution DTI. Imaging was performed at 6–12 months post-injury and findings were compared to histological analyses of Nissl, myelin, and Timm-stained preparations from the same animals. In agreement with the severity of histological damage, fractional anisotropy (FA), axial (D ||) and radial (D ⊥) diffusivities, and mean diffusivity (MD) measurements were altered in the order SE > TBI ipsilaterally > TBI contralaterally. After SE, the most severe abnormalities were found in the dentate gyrus and CA3b–c subfields, in which the mean FA was increased to 125 % (p < 0.001) and 143 % (p < 0.001) of that in controls, respectively. In both subfields, the change in FA was associated with an increase in D || (p < 0.01). In the stratum radiatum of the CA1, FA was decreased to 81 % of that in controls (p < 0.05) which was associated with an increase in D ⊥ (p < 0.01). After TBI, DTI did not reveal any major abnormalities in the dentate gyrus. In the ipsilateral CA3b–c, however, FA was increased to 126 % of that in controls (p < 0.01) and associated with a mild decrease in D ⊥ (p < 0.05). In the stratum radiatum of the ipsilateral CA1, FA was decreased to 88 % of that in controls (p < 0.05). Our data demonstrate that DTI reveals subfield-specific abnormalities in the hippocampus with remarkable qualitative and quantitative differences between the two epileptogenic etiologies, suggesting that DTI could be a valuable tool for follow-up of focal circuitry reorganization during the post-injury aftermath.

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
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

Abbreviations

D || :

Axial diffusivity

D ⊥ :

Radial diffusivity

DTI:

Diffusion tensor imaging

FA:

Fractional anisotropy

FPI:

Fluid percussion injury

MD:

Mean diffusivity

MRI:

Magnetic resonance imaging

ROI:

Region of interest

SE:

Status epilepticus

TBI:

Traumatic brain injury

References

  • Amaral DG, Insausti R (1990) Hippocampal formation. In: Paxinos G (ed) The human nervous system. Academic Press, San Diego, pp 711–755

    Chapter  Google Scholar 

  • Amaral DG, Witter MP (1989) The three-dimensional organization of the hippocampal formation: a review of anatomical data. Neuroscience 31:571–591

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Basser PJ, Pierpaoli C (1998) A simplified method to measure the diffusion tensor from seven MR images. Magn Reson Med 39:928–934

    Article  CAS  PubMed  Google Scholar 

  • Baulac M, Pitkänen A (2008) Research priorities in epilepsy for the next decade—a representative view of the European scientific community. Epilepsia

  • Beaulieu C (2002) The basis of anisotropic water diffusion in the nervous system—a technical review. NMR Biomed 15:435–455

    Article  PubMed  Google Scholar 

  • Bennett RE, Mac Donald CL, Brody DL (2012) Diffusion tensor imaging detects axonal injury in a mouse model of repetitive closed-skull traumatic brain injury. Neurosci Lett 513:160–165

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Buckmaster PS (2012) Mossy fiber sprouting in the dentate gyrus. In: Noebels JL, Avoli M, Rogawski MA, Olsen RW, Delgado-Escueta AV (eds) Jasper’s basic mechanisms of the epilepsies. Michael A Rogawski, Antonio V Delgado-Escueta, Jeffrey L Noebels, Massimo Avoli and Richard W Olsen, Bethesda

    Google Scholar 

  • Buckmaster PS, Ingram EA, Wen X (2009) Inhibition of the mammalian target of rapamycin signaling pathway suppresses dentate granule cell axon sprouting in a rodent model of temporal lobe epilepsy. J Neurosci 29(25):8259–8269

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Budde MD, Janes L, Gold E, Turtzo LC, Frank JA (2011) The contribution of gliosis to diffusion tensor anisotropy and tractography following traumatic brain injury: validation in the rat using Fourier analysis of stained tissue sections. Brain 134:2248–2260

    Article  PubMed Central  PubMed  Google Scholar 

  • Cavazos JE, Golarai G, Sutula TP (1991) Mossy fiber synaptic reorganization induced by kindling: time course of development, progression, and permanence. J Neurosci 11:2795–2803

    CAS  PubMed  Google Scholar 

  • Chan KC, Cheng JS, Fan S, Zhou IY, Yang J, Wu EX (2012) In vivo evaluation of retinal and callosal projections in early postnatal development and plasticity using manganese-enhanced MRI and diffusion tensor imaging. NeuroImage 59:2274–2283

    Article  PubMed  Google Scholar 

  • Christidi F, Bigler ED, McCauley SR, Schnelle KP, Merkley TL, Mors MB et al (2011) Diffusion tensor imaging of the perforant pathway zone and its relation to memory function in patients with severe traumatic brain injury. J Neurotrauma 28:711–725

    Article  PubMed  Google Scholar 

  • Concha L, Gross DW, Wheatley BM, Beaulieu C (2006) Diffusion tensor imaging of time-dependent axonal and myelin degradation after corpus callosotomy in epilepsy patients. NeuroImage 32:1090–1099

    Article  PubMed  Google Scholar 

  • Cross DJ, Cavazos JE (2007) Synaptic reorganization in subiculum and CA3 after early-life status epilepticus in the kainic acid rat model. Epilepsy Res 73:156–165

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Dauguet J, Peled S, Berezovskii V, Delzescaux T, Warfield SK, Born R et al (2007) Comparison of fiber tracts derived from in vivo DTI tractography with 3D histological neural tract tracer reconstruction on a macaque brain. NeuroImage 37(2):530–538

    Article  PubMed  Google Scholar 

  • de Carvalho Rangel C, Hygino Cruz LC Jr, Takayassu TC, Gasparetto EL, Domingues RC (2011) Diffusion MR imaging in central nervous system. Magn Reson Imaging Clin N Am 19:23–53

    Article  PubMed  Google Scholar 

  • de Lanerolle NC, Lee TS, Spencer DD (2012) Histopathology of human epilepsy. In: Noebels JL, Avoli M, Rogawski MA, Olsen RW, Delgado-Escueta AV (eds) Jasper’s basic mechanisms of the epilepsies. Michael A Rogawski, Antonio V Delgado-Escueta, Jeffrey L Noebels, Massimo Avoli and Richard W Olsen, Bethesda

    Google Scholar 

  • Dityatev A, Fellin T (2008) Extracellular matrix in plasticity and epileptogenesis. Neuron Glia Biol 4:235–247

    Article  PubMed  Google Scholar 

  • Galanopoulou AS, Buckmaster PS, Staley KJ, Moshe SL, Perucca E, Engel J Jr et al (2012) Identification of new epilepsy treatments: issues in preclinical methodology. Epilepsia 53:571–582

    Article  PubMed Central  PubMed  Google Scholar 

  • Hauser WA (1997) Incidence and prevalence. In: Engel J Jr, Pedley TA (eds) Epilepsy: a comprehensive textbook. Lippincott-Raven Publishers, Philadelphia, pp 47–57

    Google Scholar 

  • Hayward NM, Tuunanen PI, Immonen R, Ndode-Ekane XE, Pitkänen A, Gröhn O (2011) Magnetic resonance imaging of regional hemodynamic and cerebrovascular recovery after lateral fluid-percussion brain injury in rats. J Cereb Blood Flow Metab 31:166–177

    Article  PubMed Central  PubMed  Google Scholar 

  • Heidemann RM, Anwander A, Feiweier T, Knosche TR, Turner R (2012) k-space and q-space: combining ultra-high spatial and angular resolution in diffusion imaging using ZOOPPA at 7 T. NeuroImage 60:967–978

    Article  PubMed  Google Scholar 

  • Horsfield MA, Jones DK (2002) Applications of diffusion-weighted and diffusion tensor MRI to white matter diseases—a review. NMR Biomed 15:570–577

    Article  PubMed  Google Scholar 

  • Jenkinson M, Smith S (2001) A global optimisation method for robust affine registration of brain images. Med Image Anal 5:143–156

    Article  CAS  PubMed  Google Scholar 

  • Jenkinson M, Bannister P, Brady M, Smith S (2002) Improved optimization for the robust and accurate linear registration and motion correction of brain images. NeuroImage 17:825–841

    Article  PubMed  Google Scholar 

  • Jones DK (2004) The effect of gradient sampling schemes on measures derived from diffusion tensor MRI: a Monte Carlo study. Magn Reson Med 51(4):807–815

    Article  PubMed  Google Scholar 

  • Kaufman et al (2005) Anatomical analysis of an aye–aye brain (Daubentonia madagascariensis, primates: Prosimii) combining histology, structural magnetic resonance imaging, and diffusion-tensor imaging. Anat Rec 287A:1026–1037

    Article  Google Scholar 

  • Kelley MS, Jacobs MP, Lowenstein DH, NINDS Epilepsy Benchmark Stewards (2009) The NINDS epilepsy research benchmarks. Epilepsia 50(3):579–582

    Article  PubMed Central  PubMed  Google Scholar 

  • Kharatishvili I, Nissinen JP, McIntosh TK, Pitkänen A (2006) A model of posttraumatic epilepsy induced by lateral fluid-percussion brain injury in rats. Neuroscience 140:685–697

    Article  CAS  PubMed  Google Scholar 

  • Kharatishvili I, Immonen R, Gröhn O, Pitkänen A (2007) Quantitative diffusion MRI of hippocampus as a surrogate marker for post-traumatic epileptogenesis. Brain 130:3155–3168

    Article  PubMed  Google Scholar 

  • Kuo LW, Lee CY, Chen JH, Wedeen VJ, Chen CC, Liou HH et al (2008) Mossy fiber sprouting in pilocarpine-induced status epilepticus rat hippocampus: a correlative study of diffusion spectrum imaging and histology. NeuroImage 41:789–800

    Article  PubMed  Google Scholar 

  • Laitinen T, Sierra A, Pitkänen A, Gröhn O (2010) Diffusion tensor MRI of axonal plasticity in the rat hippocampus. NeuroImage 51:521–530

    Article  PubMed  Google Scholar 

  • Landman BA, Farrell JA, Jones CK, Smith SA, Prince JL, Mori S (2007) Effects of diffusion weighting schemes on the reproducibility of DTI-derived fractional anisotropy, mean diffusivity, and principal eigenvector measurements at 1.5T. NeuroImage 36(4):1123–1138

    Article  PubMed  Google Scholar 

  • Laurberg S, Zimmer J (1981) Lesion-induced sprouting of hippocampal mossy fiber collaterals to the fascia dentata in developing and adult rats. J Comp Neurol 200:433–459

    Article  CAS  PubMed  Google Scholar 

  • Leergaard TB, White NS, de Crespigny A, Bolstad I, D’Arceuil H, Bjaalie JG et al (2010) Quantitative histological validation of diffusion MRI fiber orientation distributions in the rat brain. PLoS ONE 5(1):e8595

    Article  PubMed Central  PubMed  Google Scholar 

  • McIntosh TK, Vink R, Noble L, Yamakami I, Fernyak S, Soares H et al (1989) Traumatic brain injury in the rat: characterization of a lateral fluid-percussion model. Neuroscience 28:233–244

    Article  CAS  PubMed  Google Scholar 

  • Mori S, Zhang J (2006) Principles of diffusion tensor imaging and its applications to basic neuroscience research. Neuron 51:527–539

    Article  CAS  PubMed  Google Scholar 

  • Nairismagi J, Pitkänen A, Narkilahti S, Huttunen J, Kauppinen RA, Gröhn OH (2006) Manganese-enhanced magnetic resonance imaging of mossy fiber plasticity in vivo. NeuroImage 30:130–135

    Article  PubMed  Google Scholar 

  • Ndode-Ekane XE, Hayward N, Gröhn O, Pitkänen A (2010) Vascular changes in epilepsy: functional consequences and association with network plasticity in pilocarpine-induced experimental epilepsy. Neuroscience 166:312–332

    Article  CAS  PubMed  Google Scholar 

  • Ni H, Kavcic V, Zhu T, Ekholm S, Zhong J (2006) Effects of number of diffusion gradient directions on derived diffusion tensor imaging indices in human brain. AJNR Am J Neuroradiol 27(8):1776–1781

    CAS  PubMed  Google Scholar 

  • Nissinen J, Lukasiuk K, Pitkänen A (2001) Is mossy fiber sprouting present at the time of the first spontaneous seizures in rat experimental temporal lobe epilepsy? Hippocampus 11:299–310

    Article  CAS  PubMed  Google Scholar 

  • Oechslin MS, Imfeld A, Loenneker T, Meyer M, Jancke L (2010) The plasticity of the superior longitudinal fasciculus as a function of musical expertise: a diffusion tensor imaging study. Front Hum Neurosci 3:76

    Article  PubMed Central  PubMed  Google Scholar 

  • Pajevic S, Pierpaoli C (1999) Color schemes to represent the orientation of anisotropic tissues from diffusion tensor data: application to white matter fiber tract mapping in the human brain. Magn Reson Med 42:526–540

    Article  CAS  PubMed  Google Scholar 

  • Parekh MB, Carney PR, Sepulveda H, Norman W, King M, Mareci TH (2010) Early MR diffusion and relaxation changes in the parahippocampal gyrus precede the onset of spontaneous seizures in an animal model of chronic limbic epilepsy. Exp Neurol 224:258–270

    Article  PubMed Central  PubMed  Google Scholar 

  • Perez Y, Morin F, Beaulieu C, Lacaille JC (1996) Axonal sprouting of CA1 pyramidal cells in hyperexcitable hippocampal slices of kainate-treated rats. Eur J Neurosci 8:736–748

    Article  CAS  PubMed  Google Scholar 

  • Pitkänen A (2010) Therapeutic approaches to epileptogenesis—hope on the horizon. Epilepsia 51(Suppl 3):2–17

    Article  PubMed Central  PubMed  Google Scholar 

  • Racine RJ (1972) Modification of seizure activity by electrical stimulation. II. Motor seizure. Electroencephalogr Clin Neurophysiol 32:281–294

    Article  CAS  PubMed  Google Scholar 

  • Reese TG, Heid O, Weisskoff RM, Wedeen VJ (2003) Reduction of eddy-current-induced distortion in diffusion MRI using a twice-refocused spin echo. Magn Res Med 49:177–182

    Article  CAS  Google Scholar 

  • Rigau V, Morin M, Rousset MC, de Bock F, Lebrun A, Coubes P et al (2007) Angiogenesis is associated with blood–brain barrier permeability in temporal lobe epilepsy. Brain 130:1942–1956

    Article  PubMed  Google Scholar 

  • Savander V, Go CG, Ledoux JE, Pitkänen A (1996) Intrinsic connections of the rat amygdaloid complex: projections originating in the accessory basal nucleus. J Comp Neurol 374:291–313

    Article  CAS  PubMed  Google Scholar 

  • Shepherd TM, Ozarslan E, King MA, Mareci TH, Blackband SJ (2006) Structural insights from high-resolution diffusion tensor imaging and tractography of the isolated rat hippocampus. NeuroImage 32:1499–1509

    Article  PubMed  Google Scholar 

  • Sidaros A, Engberg AW, Sidaros K, Liptrot MG, Herning M, Petersen P et al (2008) Diffusion tensor imaging during recovery from severe traumatic brain injury and relation to clinical outcome: a longitudinal study. Brain 131:559–572

    Article  PubMed  Google Scholar 

  • Sierra A, Laitinen T, Lehtimäki K, Rieppo L, Pitkänen A, Gröhn O (2011) Diffusion tensor MRI with tract-based spatial statistics and histology reveals undiscovered lesioned areas in kainate model of epilepsy in rat. Brain Struct Funct 216:123–135

    Article  PubMed  Google Scholar 

  • Sigal T, Shmuel M, Mark D, Gil H, Anat A (2012) Diffusion tensor imaging of corpus callosum integrity in multiple sclerosis: correlation with disease variables. J Neuroimaging 22:33–37

    Article  PubMed  Google Scholar 

  • Sloviter RS (1982) A simplified Timm stain procedure compatible with formaldehyde fixation and routine paraffin embedding of rat brain. Brain Res Bull 8:771–774

    Article  CAS  PubMed  Google Scholar 

  • Sun SW, Neil JJ, Song SK (2003) Relative indices of water diffusion anisotropy are equivalent in live and formalin-fixed mouse brains. Magn Reson Med 50:743–748

    Article  PubMed  Google Scholar 

  • Thind KK, Yamawaki R, Phanwar I, Zhang G, Wen X, Buckmaster PS (2010) Initial loss but later excess of GABAergic synapses with dentate granule cells in a rat model of temporal lobe epilepsy. J Comp Neurol 518:647–667

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Wong M (2005) Modulation of dendritic spines in epilepsy: cellular mechanisms and functional implications. Epilepsy Behav 7:569–577

    Article  PubMed  Google Scholar 

  • Yassa MA, Muftuler LT, Stark CE (2010) Ultrahigh-resolution microstructural diffusion tensor imaging reveals perforant path degradation in aged humans in vivo. Proc Natl Acad Sci USA 107:12687–12691

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Zalesky A, Fornito A, Seal ML, Cocchi L, Westin CF, Bullmore ET et al (2011) Disrupted axonal fiber connectivity in schizophrenia. Biol Psychiatry 69:80–89

    Article  PubMed  Google Scholar 

  • Zhang J, van Zijl PC, Mori S (2002) Three-dimensional diffusion tensor magnetic resonance microimaging of adult mouse brain and hippocampus. NeuroImage 15:892–901

    Article  PubMed  Google Scholar 

  • Zhang J, van Zijl PC, Laterra J, Salhotra A, Lal B, Mori S et al (2007) Unique patterns of diffusion directionality in rat brain tumors revealed by high-resolution diffusion tensor MRI. Magn Reson Med 58:454–462

    Article  PubMed Central  PubMed  Google Scholar 

  • Zhao C, Deng W, Gage FH (2008) Mechanisms and functional implications of adult neurogenesis. Cell 132(4):645–660

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by the Academy of Finland (A.S., O.G., A.P.), Sigrid Juselius Foundation (A.P.), and UEF-Brain strategic funding from the University of Eastern Finland. We thank Ms. Maarit Pulkkinen for assistance in histology, Dr. Jari Nissinen and Dr. Tamuna Bolkvadze for technical assistance, MSc Juha-Pekka Niskanen for drawing the diffusion ellipsoids, and Dr. Nick Hayward for revising the language of the manuscript.

Author information

Authors and Affiliations

  1. Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, PO Box 1627, 70211, Kuopio, Finland

    Alejandra Sierra, Teemu Laitinen, Olli Gröhn & Asla Pitkänen

  2. Department of Neurology, Kuopio University Hospital, PO Box 1777, 70211, Kuopio, Finland

    Asla Pitkänen

Authors
  1. Alejandra Sierra
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Teemu Laitinen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Olli Gröhn
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Asla Pitkänen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Asla Pitkänen.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Video 1 (MPG 1415 kb)

Supplementary Video 2 (MPG 1415 kb)

Supplementary Video 3 (MPG 1415 kb)

Supplementary Video 4 (MPG 1415 kb)

Supplementary Video 5 (MPG 1415 kb)

429_2013_683_MOESM6_ESM.tif

Supplementary Figure 1. Examples of diffusion ellipsoids prepared from the control group and from two individual rats in the SE and TBI groups. Note the region specific difference in the orientation (color of the ellipsoid) as well as axial and radial diffusivities (shape of the ellipsoid) between individual animals (TIFF 1239 kb)

Supplementary Table 1 (DOCX 16 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sierra, A., Laitinen, T., Gröhn, O. et al. Diffusion tensor imaging of hippocampal network plasticity. Brain Struct Funct 220, 781–801 (2015). https://doi.org/10.1007/s00429-013-0683-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00429-013-0683-7

Keywords

Search

Navigation