title: Lateralization of temporal lobe epilepsy using a novel uncertainty analysis of MR diffusion in hippocampus, cingulum, and fornix, and hippocampal volume and FLAIR intensity.
abstract: OBJECTIVE
  To analyze the utility of a quantitative uncertainty analysis approach for evaluation and comparison of various MRI findings for the lateralization of epileptogenicity in mesial temporal lobe epilepsy (mTLE), including novel diffusion-based analyses.
  
  
  METHODS
  We estimated the hemispheric variation uncertainty (HVU) of hippocampal T1 volumetry and FLAIR (Fluid Attenuated Inversion Recovery) intensity. Using diffusion tensor images of 23 nonepileptic subjects, we estimated the HVU levels of mean diffusivity (MD) in the hippocampus, and fractional anisotropy (FA) in the posteroinferior cingulum and crus of fornix. Imaging from a retrospective cohort of 20 TLE patients who had undergone surgical resection with Engel class I outcomes was analyzed to determine whether asymmetry of preoperative volumetrics, FLAIR intensities, and MD values in hippocampi, as well as FA values in posteroinferior cingula and fornix crura correctly predicted laterality of seizure onset. Ten of the cohort had pathologically proven mesial temporal sclerosis (MTS). Seven of these patients had undergone extraoperative electrocorticography (ECoG) for lateralization or to rule out extra-temporal foci.
  
  
  RESULTS
  HVU was estimated to be 3.1×10(-5) for hippocampal MD, 0.027 for FA in posteroinferior cingulum, 0.018 for FA in crus of fornix, 0.069 for hippocampal normalized volume, and 0.099 for hippocampal normalized FLAIR intensity. Using HVU analysis, a higher hippocampal MD value, lower FA within the posteroinferior cingulum and crus of fornix, shrinkage in hippocampal volume, and higher hippocampal FLAIR intensity were observed beyond uncertainty on the side ipsilateral to seizure onset for 10, 10, 9, 9, and 10 out of 10 pathology-proven MTS patients, respectively. Considering all 20 TLE patients, these numbers were 18, 15, 14, 13, and 16, respectively. However, consolidating the lateralization results of HVU analysis on these quantities by majority voting has detected the epileptogenic side for 19 out of 20 cases with no wrong lateralization.
  
  
  CONCLUSIONS
  The presence of MTS in TLE patients is associated with an elevated MD value in the ipsilateral hippocampus and a reduced FA value in the posteroinferior subregion of the ipsilateral cingulum and crus of ipsilateral fornix. When considering all TLE patients, among the mentioned biomarkers the hippocampal MD had the best performance with true detection rate of 90% without any wrong lateralization. The proposed uncertainty based analyses hold promise for improving decision-making for surgical resection.
authors.affiliation: Radiology Department, Henry Ford Hospital, Detroit, MI 48202, USA; Research Administration Department, Henry Ford Hospital, Detroit, MI 48202, USA. Electronic address: mohamadn@rad.hfh.edu.
authors.forename: Mohammad-Reza
authors.initials: MR
authors.lastname: Nazem-Zadeh
authors.affiliation: Neurosurgery Department, Henry Ford Hospital, Detroit, MI 48202, USA. Electronic address: jschwal1@hfhs.org.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Schwalb
authors.affiliation: Department of Clinical Neurosciences, Spectrum Health Medical Group, Grand Rapids, MI 49503, USA. Electronic address: kost.elisevich@spectrumhealth.org.
authors.forename: Kost V
authors.initials: KV
authors.lastname: Elisevich
authors.affiliation: Radiology Department, Henry Ford Hospital, Detroit, MI 48202, USA; Research Administration Department, Henry Ford Hospital, Detroit, MI 48202, USA; Neurology Department, Henry Ford Hospital, Detroit, MI 48202, USA. Electronic address: hbagher1@hfhs.org.
authors.forename: Hassan
authors.initials: H
authors.lastname: Bagher-Ebadian
authors.affiliation: Radiology Department, Henry Ford Hospital, Detroit, MI 48202, USA; Research Administration Department, Henry Ford Hospital, Detroit, MI 48202, USA; School of Computer Science, Wayne State University, Detroit, MI 48202, USA. Electronic address: nasimh@rad.hfh.edu.
authors.forename: Hajar
authors.initials: H
authors.lastname: Hamidian
authors.affiliation: Computational Radiology Laboratory, Dept. of Radiology, Children's Hospital, Boston, MA 02115, USA. Electronic address: alireza.akhondi-asl@childrens.harvard.edu.
authors.forename: Ali-Reza
authors.initials: AR
authors.lastname: Akhondi-Asl
authors.affiliation: Radiology Department, Henry Ford Hospital, Detroit, MI 48202, USA; Research Administration Department, Henry Ford Hospital, Detroit, MI 48202, USA; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: kjafari@nmr.mgh.harvard.edu.
authors.forename: Kourosh
authors.initials: K
authors.lastname: Jafari-Khouzani
authors.affiliation: Radiology Department, Henry Ford Hospital, Detroit, MI 48202, USA; Research Administration Department, Henry Ford Hospital, Detroit, MI 48202, USA; CIPCE, School of Electrical and Computer Engineering, University of Tehran, Tehran, Iran. Electronic address: hamids@rad.hfh.edu.
authors.forename: Hamid
authors.initials: H
authors.lastname: Soltanian-Zadeh
mesh_terms: D000328:Adult; D016880:Anisotropy; D015331:Cohort Studies; D056324:Diffusion Tensor Imaging; D004833:Epilepsy, Temporal Lobe / Q000473:pathology*; D005260:Female; D020712:Fornix, Brain / Q000473:pathology*; D007839:Functional Laterality; D006179:Gyrus Cinguli / Q000473:pathology*; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D008297:Male; D059906:Neuroimaging
keywords: Cingulum; Diffusion MRI; Fornix; Hippocampus; Seizure lateralization; Temporal lobe epilepsy