Abstracts

Rationale: Hippocampal sclerosis subtypes (ILAE type I-III HS) have distinct prognoses for surgical cure following temporal lobectomy.  Subtype diagnosis is currently not possible preoperatively, and this prognostic information is therefore not currently used to guide surgical decision making.  In vivo hippocampal subfield segmentation is a promising tool to allow in vivo diagnosis of HS subtypes with a view towards prognostication of seizure-free outcomes.  In the present study, we therefore aimed to: A) Develop a novel histology-based method for hippocampal subfield segmentation; and B) Apply the novel method in one patient with unilateral temporal lobe epilepsy and hippocampal sclerosis. Methods: A) Ultra-high resolution ex vivo MRI was performed on six whole cadaveric hippocampal specimens, which were then divided into 22 blocks and histologically processed.  A segmentation method was developed using mean percentage of the total SLM distance to define subfield boundaries. Boundary distances and subfield areas on histology were then determined using the novel method and compared to the gold standard histological measurements. The novel method was then used to determine ex vivo MRI measures of subfield boundaries and areas, which were compared to histological measurements (Figure 1). B) High resolution in vivo MRI (native resolution 0.52×0.68×1.0 mm3) was performed on a 4.7 Tesla MRI (Figure 2). Hippocampal subfields were segmented according to the novel method on contiguous slices through the hippocampal body bilaterally. Visualization of the SLM was quantified according to a published hippocampal internal architecture scoring system (ranging from 0 to 4).  Intra- and inter-rater reliability was assessed using the intra-class correlation coefficient (ICC).  Subfield areas for Subiculum, CA1, CA2, and CA3/CA4/DG were measured on each slice throughout the hippocampal body.   Results: A) For direct histological measurements, the mean percentages of total SLM distance were: Subiculum/CA1 = 9.7%, CA1/CA2 = 78.4%, CA2/CA3 = 97.5%. When applied to histology, the novel method provided accurate measures for CA1/CA2 (ICC = 0.93) and CA2/CA3 (ICC = 0.97) boundaries, but not for the Subiculum/CA1 (ICC = -0.04) boundary. Ex vivo MRI measurements using the novel method were linearly related to direct measurements of SLM length (r2 = 0.58), CA1/CA2 boundary (r2 = 0.39) and CA2/CA3 boundary (r2 = 0.47), but not for Subiculum/CA1 boundary (r2 = 0.01). B)  Mean Internal architecture scores were high (3.6) for controls, intermediate (3.1) for TLE contralateral to MTS and lowest for TLE ipsilateral to MTS (1.7).  Interrater reliability of SLM segmentation was demonstrated to correlate with internal architecture score and was highest for controls, although reliability was still reasonable for TLE contralateral and ipsilateral to MTS. Conclusions: We used ex vivo MRI and histology of cadaveric hippocampi to develop a novel segmentation protocol for the hippocampal body.  The novel method utilized two anatomical landmarks, SLM & DG, and provided accurate measurements of CA1, CA2, and CA3/CA4/DG subfields in comparison to the gold standard histological measurements.  Our preliminary results suggest that the novel method can be applied reliably in vivo despite impaired visualization of the SLM in TLE.  These data support further development of the method for preoperative diagnosis of HS subtypes. Funding: The study was funded by an operating grant held by DWG from the Canadian Institutes for Health Research (funding reference number 81083).  TAS was supported by a post-graduate fellowship award from Eisai and the Canadian League Against Epilepsy (CLAE).  The funding sources had no involvement in this study aside from providing financial support.