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Diffusion tensor MRI with tract-based spatial statistics and histology reveals undiscovered lesioned areas in kainate model of epilepsy in rat

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Abstract

In this study, we used tract-based spatial statistics (TBSS) to analyze diffusion tensor MR imaging (DTI) data acquired from the rat brain, ex vivo, for the first time. The aim was to highlight potential changes in the whole brain anatomy in the kainic acid model of epilepsy, and further characterize the changes with histology. Increased FA was observed in dorsal endopiriform nucleus, external capsule, corpus callosum, dentate gyrus, thalamus, and optic tract. A decrease in FA was seen in the horizontal limb of the diagonal band, stria medullaris, habenula, entorhinal cortex, and superior colliculus. Some of the areas have been described in kainic acid model before. However, we also found regions that to our knowledge have not been previously reported to undergo structural changes, in this model, including stria medullaris, nucleus of diagonal band, habenula, superior colliculus, external capsule, corpus callosum, and optic tract. Four of the areas highlighted in TBSS (dentate gyrus, entorhinal cortex, thalamus and stria medullaris) were analyzed in more detail with Nissl, Timm, and myelin-stained histological sections, and with polarized light microscopy. TBSS together with targeted histology confirmed that DTI changes were associated with altered myelination, neurodegeneration, and/or calcification of the tissue. Our data demonstrate that DTI in combination with TBSS has a great potential to facilitate the discovery of previously undetected anatomical changes in animal models of brain diseases.

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Abbreviations

D|| :

Axial diffusivity

D⊥ :

Radial diffusivity

DTI:

Diffusion tensor imaging

FA:

Fractional anisotropy

KA:

Kainic acid

MD:

Mean diffusivity

PLM:

Polarized light microscopy

ROI:

Region of interest

TBSS:

Tract-based spatial statistics

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Acknowledgments

This work was supported by Academy of Finland and Sigrid Juselius Foundation. We thank Ms. Maarit Pulkkinen for assistance in histology, Dr. Jari Nissinen for technical assistance, MSc Kari Mauranen for consultation in statistical analysis, and MSc Nick Hayward for revising the language of the manuscript.

Conflict of interest

The authors declare no competing financial interests.

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Authors and Affiliations

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

    Alejandra Sierra, Teemu Laitinen, Asla Pitkänen & Olli Gröhn

  2. Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, 70211, Kuopio, Finland

    Kimmo Lehtimäki

  3. Department of Physics and Mathematics, University of Eastern Finland, P.O. Box 1627, 70211, Kuopio, Finland

    Lassi Rieppo

  4. Department of Anatomy, Institute of Biomedicine, University of Eastern Finland, P.O. Box 1627, 70211, Kuopio, Finland

    Lassi Rieppo

  5. Department of Neurology, Kuopio University Hospital, P.O. Box 1777, 70211, Kuopio, Finland

    Asla Pitkänen

Authors
  1. Alejandra Sierra
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  2. Teemu Laitinen
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  3. Kimmo Lehtimäki
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  4. Lassi Rieppo
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  5. Asla Pitkänen
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  6. Olli Gröhn
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Corresponding author

Correspondence to Olli Gröhn.

Additional information

A. Sierra and T. Laitinen shared first authorship.

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Sierra, A., Laitinen, T., Lehtimäki, K. et al. 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 (2011). https://doi.org/10.1007/s00429-010-0299-0

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  • DOI: https://doi.org/10.1007/s00429-010-0299-0

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