Hemispheric Regional Based Analysis of Diffusion Tensor Imaging and Diffusion Tensor Tractography in Patients with Temporal Lobe Epilepsy and Correlation with Patient outcomes

www.nature.com/scientificreports OPEN Received: 30 May 2018 Accepted: 16 November 2018 Published: xx xx xxxx Hemispheric Regional Based Analysis of Diffusion Tensor Imaging and Diffusion Tensor Tractography in Patients with Temporal Lobe Epilepsy and Correlation with Patient outcomes Mahdi Alizadeh1,2, Lauren Kozlowski3, Jennifer Muller1,2, Neha Ashraf1, Shiva Shahrampour2, Feroze B. Mohamed2, Chengyuan Wu1,2 & Ashwini Sharan1,2 Imaging in the field of epilepsy surgery remains an essential tool in terms of its ability to identify regions where the seizure focus might present as a resectable area. However, in many instances, an obvious structural abnormality is not visualized. This has created the opportunity for new approaches and imaging innovation in the field of epilepsy, such as with Diffusion Tensor Imaging (DTI) and Diffusion Tensor Tractography (DTT). In this study, we aim to evaluate the use of DTI and DTT as a predictive model in the field of epilepsy, specifically Temporal Lobe Epilepsy (TLE), and correlate their clinical significance with respect to postsurgical outcomes. A hemispheric based analysis was used to compare the tract density, as well as DTI indices of the specific regions of interest from the pathologic hemisphere to the healthy hemisphere in TLE patients. A total of 22 patients with TLE (12 males, 10 females, 22–57 age range) underwent either a craniotomy, Anterior Temporal Lobectomy (ATL), or a less invasive method of Selective Laser Amygdalohippocampectomy (SLAH) and were imaged using 3.0 T Philips Achieva MR scanner. Of the participants, 12 underwent SLAH while 10 underwent ATL. The study was approved by the institutional review board of Thomas Jefferson University Hospital. Informed consent was obtained from all patients. All patients had a diagnosis of TLE according to standard clinical criteria. DTI images were acquired axially in the same anatomical location prescribed for the T1-weighted images. The raw data set consisting of diffusion volumes were first corrected for eddy current distortions and motion artifacts. Various DTI indices such as Fractional Anisotropy (FA), Mean Diffusivity (MD), Radial Diffusivity (RD) and Axial Diffusivity (AD) were estimated and co-registered to the brain parcellation map obtained by freesurfer. 16 consolidated cortical and subcortical regions were selected as regions of interest (ROIs) by a functional neurosurgeon and DTI values for each ROI were calculated and compared with the corresponding ROI in the opposite hemisphere. Also, track density imaging (TDI) of 68 white matter parcels were generated using fiber orientation distribution (FOD) based deterministic fiber tracking and compared with contralateral side of the brain in each epileptic group: left mesial temporal sclerosis (LMTS) and right MTS (RMTS)). In patients with LMTS, MD and RD values of the left hippocampus decreased significantly using two-tailed t-test (p = 0.03 and p = 0.01 respectively) compared to the right hippocampus. Also, RD showed a marginally significant decrease in left amygdala (p = 0.05). DTT analysis in LMTS shows a marginally significant decrease in the left white matter supramarginal parcel (p = 0.05). In patients with RMTS, FA showed a significant decrease in the ipsilateral mesial temporal lobe (p = 0.02), parahippocampal area (p = 0.03) and thalamus (p = 0.006). 1 Department of Neurosurgery, Thomas Jefferson University, Philadelphia, PA, USA. 2Jefferson Integrated Magnetic Resonance Imaging Center, Department of Radiology, Thomas Jefferson University, Philadelphia, PA, USA. 3Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA. Correspondence and requests for materials should be addressed to M.A. (email: ) Scientific Reports | (2019) 9:215 | DOI:10.1038/s41598-018-36818-x 1 www.nature.com/scientificreports/ RD showed a marginally significant increase in the ipsilateral hippocampus (p = 0.05) and a significant increase in the ipsilateral parahippocampal area (p = 0.03). Also, tract density of the ipsilateral white matter inferior parietal parcel showed a marginally significant increase compared to the contralateral side (p = 0.05). With respect to postsurgical outcomes, we found an association between residual seizures and tract density in five white matter segments including ipsilateral lingual (p = 0.04), ipsilateral temporal pole (p = 0.007), ipsilateral pars opercularis (p = 0.03), ipsilateral inferior parietal (p = 0.04) and contralateral frontal pole (p = 0.04). These results may have the potential to be developed into imaging prognostic markers of postoperative outcomes and provide new insights for why some patients with TLE continue to experience postoperative seizures if pathological/clinical correlates are further confirmed. Neurologic diseases, such as epilepsy, often cause long-term debilitation for patients leading to deficits in brain function and frequent seizures1. Although epilepsy may arise from a vast number of causes including genetic, immune, and infectious, temporal lobe epilepsy (TLE) is among one of the most common types of this disease. Patients with TLE experience chronic, recurrent focal seizures that are typically unprovoked; however, patients with TLE do not always have simple partial seizures, and may also experience complex partial seizures that spread to other regions of the brain2. TLE is typically managed medically at the onset of the disease with various antiepileptic medications, but for those patients with intractable seizures failing to respond to numerous antiepileptic agents, surgery such as anterior temporal lobectomy (ATL) or selective laser amygdalohippocampectomy (SLAH) may be considered2. As previously mentioned, there are numerous causes that may lead to TLE, but the most frequent disease etiology that is refractory to medical management and responsive to surgical management is mesial temporal sclerosis (MTS), also commonly known as hippocampal sclerosis (HS)3. Imaging in the field of epilepsy has been a lasting challenge, specifically, with regards to identifying the seizure focus as a resectable area for potential procedures4. This has created the opportunity for new approaches and imaging innovation in the field of epilepsy such as diffusion tensor imaging (DTI). DTI measures the magnitude and direction of the diffusion of water along 3 principle eigenvectors (x, y and z directions), and also provides insight into the microstructure of both gray and white matter by measuring water diffusion5. The information provided by DTI acquisition allows for the quantification of various diffusion parametric maps as well as the generation of 3-dimentional (3D) white matter fiber tractography5. Diffusion tensor tractography (DTT) is a computational procedure that reconstructs major fiber bundles in 3D space based on their anisotropy properties. It is a visual and quantitative tool for presenting white matter tracts from DTI data6,7. White matter stu (...truncated)