{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T14:14:48Z","timestamp":1780496088519,"version":"3.54.1"},"reference-count":64,"publisher":"MIT Press","license":[{"start":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T00:00:00Z","timestamp":1729468800000},"content-version":"vor","delay-in-days":294,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["direct.mit.edu"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,11,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Surgical resection is the method of choice for treating drug-resistant focal temporal lobe epilepsy (TLE). Postsurgical outcomes are better when magnetic resonance imaging (MRI) findings can localize the seizure focus for resection. However, many patients are MR-negative, meaning the focus cannot be differentiated from normal tissue in relaxation-weighted MRI. Diffusion MRI shows promise as a preoperative marker of neuronal abnormalities due to its sensitivity to cellular changes such as axon damage, indexed by fractional anisotropy. Microscopic fractional anisotropy is a recently introduced diffusion MRI metric that is sensitive to axon integrity regardless of axon orientation in both gray and white matter. In contrast, regular fractional anisotropy is only sensitive to axon integrity in coherently oriented bundles of fibers. This work investigated whether microscopic fractional anisotropy is sensitive to hippocampal abnormalities in drug-resistant TLE. Diffusion MRI was performed on a 3T scanner in 19 patients (age = 31 \u00b1 10 years) with drug-resistant TLE (of which 10 were MR-negative) and 18 healthy volunteers (age = 38 \u00b1 15). A deep-learning method was employed to segment the hippocampus into smaller subregions corresponding to the subiculum, cornu ammonis (CA) 1, CA2\/3, and CA4 plus dentate gyrus (DG). Mean measurements of subregion volume, diffusivity, fractional anisotropy, and microscopic fractional anisotropy were compared between cohorts. In a subset of the TLE cohort suspected to have unilateral pathology (n = 15, age = 32 \u00b1 10 years), the percentage differences between measurements ipsilateral and contralateral to the epileptogenic zone were evaluated to assess asymmetry. Microscopic fractional anisotropy was reduced in the hippocampus of drug-resistant TLE patients relative to healthy volunteers. In subregion-specific analysis, microscopic fractional anisotropy was significantly reduced in only the CA4\/DG region in patients compared with healthy volunteers, after corrections for multiple comparisons. In the 15 patients with suspected unilateral pathology, microscopic fractional anisotropy was reliably and statistically lower in the ipsilateral CA4\/DG region than in the contralateral side. Significant differences were not observed between TLE patients and healthy volunteers, or between hemispheres for patients with suspected unilateral pathology, for the fractional anisotropy or volume metrics. Diffusion MRI may complement standard imaging procedures by detecting abnormalities in MRI-negative patients. Due to its ability to detect abnormality regardless of axon orientation, microscopic fractional anisotropy may improve seizure focus localization in surgical candidates.<\/jats:p>","DOI":"10.1162\/imag_a_00356","type":"journal-article","created":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T16:00:49Z","timestamp":1729526449000},"update-policy":"https:\/\/doi.org\/10.1162\/mitpressjournals.corrections.policy","source":"Crossref","is-referenced-by-count":2,"title":["Hippocampal microscopic fractional anisotropy is reduced in temporal lobe epilepsy"],"prefix":"10.1162","volume":"2","author":[{"given":"Nico J.J.","family":"Arezza","sequence":"first","affiliation":[{"name":"Department of Medical Biophysics, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada"},{"name":"Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hana H.","family":"Abbas","sequence":"additional","affiliation":[{"name":"Department of Psychology, Western University, London, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Chadwick","sequence":"additional","affiliation":[{"name":"Department of Psychology, Western University, London, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid S.","family":"Johnsrude","sequence":"additional","affiliation":[{"name":"Department of Psychology, Western University, London, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge G.","family":"Burneo","sequence":"additional","affiliation":[{"name":"Epilepsy Program, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada"},{"name":"Neuroepidemiology Unit, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Suller Marti","sequence":"additional","affiliation":[{"name":"Epilepsy Program, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada"},{"name":"Pediatric Department, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali R.","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Medical Biophysics, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada"},{"name":"Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corey A.","family":"Baron","sequence":"additional","affiliation":[{"name":"Department of Medical Biophysics, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada"},{"name":"Robarts Research Institute, Schulich School of Medicine and Dentistry, Western 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