Research ArticleEpilepsy

Glutamate imaging (GluCEST) lateralizes epileptic foci in nonlesional temporal lobe epilepsy

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Science Translational Medicine  14 Oct 2015:
Vol. 7, Issue 309, pp. 309ra161
DOI: 10.1126/scitranslmed.aaa7095
  • Fig. 1. The distribution of epilepsy patients worldwide, with details for those with drug-resistant epilepsy.
  • Fig. 2. Axial sections from four patients with drug-resistant TLE, showing the GluCEST signal.

    (A) A 40-year-old female with nonlesional right TLE, with a visible increase in the GluCEST signal in the right hippocampus. (B) A 47-year-old female with nonlesional right TLE, with a visible increase in the GluCEST signal in the right hippocampus. (C) A 25-year-old female with nonlesional left TLE, with a visible increase in the GluCEST signal in the left hippocampus. (D) A 47-year-old male with nonlesional left TLE, with a visible increase in the GluCEST signal in the left hippocampus.

  • Fig. 3. Increased glutamate in the hippocampus ipsilateral to seizure onset, as measured by GluCEST.

    GluCEST contrast in the hippocampi ipsilateral and contralateral to seizure onset, as measured by percentage displaced water protons. Green and gray portions of each box represent the second and third quartile values, respectively; the upper and lower range of values is indicated by whiskers. P = 0.011, one-tailed t test.

  • Fig. 4. Increased glutamate in the hippocampus ipsilateral to seizure onset in a patient with right TLE.

    Single-voxel proton magnetic resonance spectroscopy (1H MRS) was performed individually on the left and right hippocampi of the nonlesional right TLE subject (Cho, choline; mI, myo-inositol). Heights of the peaks were measured in arbitrary units (A.U.).

  • Fig. 5. Intracranial EEG data from patient 4, with nonlesional TLE arising from right hippocampus.

    Background traces show EEG data from the individual contacts of subdural and depth electrodes in patient 4, indicating the localization of seizure onset to the CA1 region of the hippocampus (red arrow). (A, C, and E) Three MRI sections through the hippocampus and amygdala showing the multicontact right mesial temporal depth electrode [each contact of the electrode is shown as a yellow square; seizure onset electrode is the electrode most distal from scalp (first electrode from left)]. (B, D, and F) Duplicate of the sections shown in (A), (C), and (E) with segmentation of hippocampal subfields superimposed on the image. Red, CA1; green, dentate gyrus; dark blue, Brodmann area 36; tan, CA3; light blue, Brodmann area 35; violet, subiculum. Segmentation was performed as described (47). (G) Right lateral view of the reconstructed MRI brain image of patient 4 (39). The positions of the right hemisphere electrodes are shown in green, coregistered with the MRI image. The multicontact electrodes used for seizure localization are labeled [Depths, depth electrodes (right hippocampal and amygdalar); RPT, right posterior temporal electrode; RMT, right mid-temporal electrode; RAT, right anterior temporal electrode; RAF, right anterior frontal electrode]. The unlabeled electrodes were not used in the analysis described in this article.

  • Table 1. Summary of GluCEST findings in nonlesional patients with TLE.

    Comparisons are made between regions ipsilateral and contralateral to seizure onset.

    Bilateral regions testedTwo-sample paired t test
    for means, comparing
    ipsilateral versus contralateral
    GluCEST values ipsilateral
    (%), range of values
    GluCEST values contralateral
    (%), range of values
    Ipsilateral-contralateral
    (%), range of values
    HippocampiP = 0.011* (one-tailed)8.69–11.167.41–10.320.46 to 1.28
    Hippocampal headsP = 0.03*9.06–12.367.59–10.87−0.02 to 1.53
    Hippocampal tailsP = 0.118.41–10.157.24–10.53−0.38 to 1.17
    HemispheresP = 0.197.47–7.826.49–7.97−0.50 to 0.98
    Hemispheres excluding
    occipital lobe
    P = 0.118.28–9.497.90–9.24−0.09 to 0.73

    *Significant with P < 0.05; n = 4.

    • Table 2. Epilepsy patient clinical information.

      SPS, simple partial seizure; CPS, complex partial seizures; GTC, generalized tonic clonic seizure.

      Patient
      number
      AgeGenderClinical
      MRI
      FDG-PETDuration of
      seizures
      Seizure
      frequency
      Seizure
      localization
      140FemaleNormalMild right anterior temporal
      hypometabolism
      6 years1 CPS/month, occasional
      CPS clusters
      Right temporal
      (scalp EEG)
      225FemaleNormalPending2.5 years3 CPS/weekLeft temporal (scalp EEG)
      347MaleNormalNone40 years1–2 CPS/yearLeft temporal (scalp EEG)
      447FemaleNormalRight temporal
      hypometabolism
      27 years2–3 CPS/week 1–2 GTC/monthRight temporal
      (intracranial EEG)*

      *Underwent right temporal lobectomy.

      Supplementary Materials

      • www.sciencetranslationalmedicine.org/cgi/content/full/7/309/309ra161/DC1

        Table S1. Epileptic subjects’ demographics and clinical information.

        Table S2. Control subjects’ demographics and summary of data.

        Table S3. Hippocampal volume, GluCEST, and MRS data in epilepsy patients.

        Fig. S1. GluCEST and MRS data in control subjects.

        Fig. S2. GluCEST and MRS data in epilepsy subjects.

        Data S1. Fig. S1 High-resolution controls (Excel file).

        Data S2. Fig. S2 High-resolution patients (Excel file).

      • Supplementary Material for:

        Glutamate imaging (GluCEST) lateralizes epileptic foci in nonlesional temporal lobe epilepsy

        Kathryn Adamiak Davis,* Ravi Prakash Reddy Nanga, Sandhitsu Das, Stephanie H. Chen, Peter N. Hadar, John R. Pollard, Timothy H. Lucas, Russell T. Shinohara, Brian Litt, Hari Hariharan, Mark A. Elliott, John A. Detre, Ravinder Reddy*

        *Corresponding author. E-mail: kathryn.davis{at}uphs.upenn.edu (K.A.D.); krr{at}mail.med.upenn.edu (R.R.)

        Published 14 October 2015, Sci. Transl. Med. 7, 309ra161 (2015)
        DOI: 10.1126/scitranslmed.aaa7095

        This PDF file includes:

        • Table S1. Epileptic subjects’ demographics and clinical information.
        • Table S2. Control subjects’ demographics and summary of data.
        • Table S3. Hippocampal volume, GluCEST, and MRS data in epilepsy patients.
        • Fig. S1. GluCEST and MRS data in control subjects.
        • Fig. S2. GluCEST and MRS data in epilepsy subjects.

        [Download PDF]

        Other Supplementary Material for this manuscript includes the following:

        • Data S1. Fig. S1 High-resolution controls (Excel file).
        • Data S2. Fig. S2 High-resolution patients (Excel file).

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