Statistical Structural Analysis of Familial Spontaneous Epileptic Cats Using Voxel-Based Morphometry

Abstract

Voxel-based morphometry (VBM) based on high resolution three-dimensional data of magnetic resonance imaging has been developed as a statistical morphometric imaging analysis method to locate brain abnormalities in humans. Recently, VBM has been used for human patients with psychological or neurological disorders such as Alzheimer's disease, Parkinson's disease, and epilepsy. Traditional volumetry using region of interest (ROI) is performed manually and the observer needs detailed knowledge of the neuroanatomy having to trace objects of interest on many slices which can cause artificial errors. In contrast, VBM is an automatic technique that has less observer biases compared to the ROI method. In humans, VBM analysis is performed in patients with epilepsy to detect accurately structural abnormalities. Familial spontaneous epileptic cats (FSECs) have been developed as an animal model of mesial temporal lobe epilepsy. In FSECs, hippocampal asymmetry had been detected using three-dimensional magnetic resonance (MR) volumetry based on the ROI method. In this study, we produced a standard template of the feline brain and compared FSECs and healthy cats using standard VBM analysis. The feline standard template and tissue probability maps were created using 38 scans from 14 healthy cats. Subsequently, the gray matter was compared between FSECs (n = 25) and healthy controls (n = 12) as group analysis and between each FSEC and controls as individual analysis. The feline standard template and tissue probability maps could be created using the VBM tools for humans. There was no significant reduction of GM in the FSEC group compared to the control group. However, 5/25 (20%) FSECs showed significant decreases in the hippocampal and/or amygdaloid regions in individual analysis. Here, we established the feline standard templates of the brain that can be used to determine accurately abnormal zones. Furthermore, like MR volumetry, VBM identified morphometric changes in the hippocampus and/or amygdala in some FSECs.

Focal Cortical Resection and Hippocampectomy in a Cat With Drug-Resistant Structural Epilepsy

“…The volumes of the right and left hippocampi were measured by 3D volumetry using 3D T2W imaging as 0.119 and 0.24 cm 3 , respectively (reference range of the feline unilateral hippocampus is 0.227 ± 0.02 cm 3 ) (Figure 3A) (26). Voxel-based morphometry analysis revealed a significantly decreased volume of the right hippocampus and temporo-occipital cortex (Figure 3B) and increased volume of the right lateral ventricle compared with reference feline brains (29). There was no evidence of hemorrhage on T2 * W images.…”

“…When the cat reached the age of 12 years, we decided to perform epilepsy surgery due to the following reasons: (1) the seizures frequently clustered and developed into status epilepticus; (2) further ASDs might not be effective; (3) the cost for medications was increasing constantly; and (4) preparations to perform intracranial EEG and epilepsy surgery were made in our previous studies of epilepsy (24)(25)(26)(27)(28)(29), and a video-EEG monitoring system and surgical microscope were installed in our laboratory.…”

“…The MRI sequences are summarized in Supplementary Data 1 . 3D T2W images were used for hippocampal volumetry by the semiautomatic region of interest method ( 26 ), and 3D T1W images were also used for statistical analysis using voxel-based morphometry ( 29 ). As described above, MRI revealed the right hippocampal and temporo-occipital atrophy without apparent signal changes on T1W, T2W, FLAIR, and contrast-enhanced T1W imaging ( Figure 2 ).…”

“…Under such a background, hippocampectomy, a type of resection surgery, would be naturally expected to be a surgical option for drugresistant FTLE. Methodologies to detect the epileptogenic zone in FTLE using familial epileptic cats (24)(25)(26)(27)(28)(29) and a cadaveric study of feline hippocampectomy (17) have been reported.…”

Partial cortico-hippocampectomy in cats, as therapy for refractory temporal epilepsy: A descriptive cadaveric study

“…Hippocampal hyperintensities in T2-weighted and fluid-attenuated inversion recovery (FLAIR) images, as well as hippocampal contrast enhancement, seem to be significantly associated with HS [ 15 ]. Volumetric analysis of the hippocampus based on MRI images allows the determination of hippocampal atrophy, which can be another feature of HS [ 16 , 17 ]. In order to improve the detection of hippocampal pathology in MRI, optimized epilepsy protocols have been developed [ 18 ].…”