Clinical evaluation of automated quantitative MRI reports for assessment of hippocampal sclerosis.

OBJECTIVES: Hippocampal sclerosis (HS) is a common cause of temporal lobe epilepsy. Neuroradiological practice relies on visual assessment, but quantification of HS imaging biomarkers-hippocampal volume loss and T2 elevation-could improve detection. We tested whether quantitative measures, contextualised with normative data, improve rater accuracy and confidence. METHODS: Quantitative reports (QReports) were generated for 43 individuals with epilepsy (mean age ± SD 40.0 ± 14.8 years, 22 men; 15 histologically unilateral HS; 5 bilateral; 23 MR-negative). Normative data was generated from 111 healthy individuals (age 40.0 ± 12.8 years, 52 men). Nine raters with different experience (neuroradiologists, trainees, and image analysts) assessed subjects' imaging with and without QReports. Raters assigned imaging normal, right, left, or bilateral HS. Confidence was rated on a 5-point scale. RESULTS: Correct designation (normal/abnormal) was high and showed further trend-level improvement with QReports, from 87.5 to 92.5% (p = 0.07, effect size d = 0.69). Largest magnitude improvement (84.5 to 93.8%) was for image analysts (d = 0.87). For bilateral HS, QReports significantly improved overall accuracy, from 74.4 to 91.1% (p = 0.042, d = 0.7). Agreement with the correct diagnosis (kappa) tended to increase from 0.74 ('fair') to 0.86 ('excellent') with the report (p = 0.06, d = 0.81). Confidence increased when correctly assessing scans with the QReport (p < 0.001, η2p = 0.945). CONCLUSIONS: QReports of HS imaging biomarkers can improve rater accuracy and confidence, particularly in challenging bilateral cases. Improvements were seen across all raters, with large effect sizes, greatest for image analysts. These findings may have positive implications for clinical radiology services and justify further validation in larger groups. KEY POINTS: • Quantification of imaging biomarkers for hippocampal sclerosis-volume loss and raised T2 signal-could improve clinical radiological detection in challenging cases. • Quantitative reports for individual patients, contextualised with normative reference data, improved diagnostic accuracy and confidence in a group of nine raters, in particular for bilateral HS cases. • We present a pre-use clinical validation of an automated imaging assessment tool to assist clinical radiology reporting of hippocampal sclerosis, which improves detection accuracy.

Voxel-based magnetic resonance image postprocessing in epilepsy.

OBJECTIVE: Although the general utility of voxel-based processing of structural magnetic resonance imaging (MRI) data for detecting occult lesions in focal epilepsy is established, many differences exist among studies, and it is unclear which processing method is preferable. The aim of this study was to compare the ability of commonly used methods to detect epileptogenic lesions in magnetic resonance MRI-positive and MRI-negative patients, and to estimate their diagnostic yield. METHODS: We identified 144 presurgical focal epilepsy patients, 15 of whom had a histopathologically proven and MRI-visible focal cortical dysplasia; 129 patients were MRI negative with a clinical hypothesis of seizure origin, 27 of whom had resections. We applied four types of voxel-based morphometry (VBM), three based on T1 images (gray matter volume, gray matter concentration, junction map [JM]) and one based on normalized fluid-attenuated inversion recovery (nFSI). Specificity was derived from analysis of 50 healthy controls. RESULTS: The four maps had different sensitivity and specificity profiles. All maps showed detection rates for focal cortical dysplasia patients (MRI positive and negative) of >30% at a strict threshold of p < 0.05 (family-wise error) and >60% with a liberal threshold of p < 0.0001 (uncorrected), except for gray matter volume (14% and 27% detection rate). All maps except nFSI showed poor specificity, with high rates of false-positive findings in controls. In the MRI-negative patients, absolute detection rates were lower. A concordant nFSI finding had a significant positive odds ratio of 7.33 for a favorable postsurgical outcome in the MRI-negative group. Spatial colocalization of JM and nFSI was rare, yet showed good specificity throughout the thresholds. SIGNIFICANCE: All VBM variants had specific diagnostic properties that need to be considered for an adequate interpretation of the results. Overall, structural postprocessing can be a useful tool in presurgical diagnostics, but the low specificity of some maps has to be taken into consideration.

Working memory network plasticity after anterior temporal lobe resection: a longitudinal functional magnetic resonance imaging study.

Working memory is a crucial cognitive function that is disrupted in temporal lobe epilepsy. It is unclear whether this impairment is a consequence of temporal lobe involvement in working memory processes or due to seizure spread to extratemporal eloquent cortex. Anterior temporal lobe resection controls seizures in 50-80% of patients with drug-resistant temporal lobe epilepsy and the effect of surgery on working memory are poorly understood both at a behavioural and neural level. We investigated the impact of temporal lobe resection on the efficiency and functional anatomy of working memory networks. We studied 33 patients with unilateral medial temporal lobe epilepsy (16 left) before, 3 and 12 months after anterior temporal lobe resection. Fifteen healthy control subjects were also assessed in parallel. All subjects had neuropsychological testing and performed a visuospatial working memory functional magnetic resonance imaging paradigm on these three separate occasions. Changes in activation and deactivation patterns were modelled individually and compared between groups. Changes in task performance were included as regressors of interest to assess the efficiency of changes in the networks. Left and right temporal lobe epilepsy patients were impaired on preoperative measures of working memory compared to controls. Working memory performance did not decline following left or right temporal lobe resection, but improved at 3 and 12 months following left and, to a lesser extent, following right anterior temporal lobe resection. After left anterior temporal lobe resection, improved performance correlated with greater deactivation of the left hippocampal remnant and the contralateral right hippocampus. There was a failure of increased deactivation of the left hippocampal remnant at 3 months after left temporal lobe resection compared to control subjects, which had normalized 12 months after surgery. Following right anterior temporal lobe resection there was a progressive increase of activation in the right superior parietal lobe at 3 and 12 months after surgery. There was greater deactivation of the right hippocampal remnant compared to controls between 3 and 12 months after right anterior temporal lobe resection that was associated with lesser improvement in task performance. Working memory improved after anterior temporal lobe resection, particularly following left-sided resections. Postoperative working memory was reliant on the functional capacity of the hippocampal remnant and, following left resections, the functional reserve of the right hippocampus. These data suggest that working memory following temporal lobe resection is dependent on the engagement of the posterior medial temporal lobes and eloquent cortex.

Automated hippocampal segmentation in patients with epilepsy: available free online.

PURPOSE: Hippocampal sclerosis, a common cause of refractory focal epilepsy, requires hippocampal volumetry for accurate diagnosis and surgical planning. Manual segmentation is time-consuming and subject to interrater/intrarater variability. Automated algorithms perform poorly in patients with temporal lobe epilepsy. We validate and make freely available online a novel automated method. METHODS: Manual hippocampal segmentation was performed on 876, 3T MRI scans and 202, 1.5T scans. A template database of 400 high-quality manual segmentations was used to perform automated segmentation of all scans with a multi-atlas-based segmentation propagation method adapted to perform label fusion based on local similarity to ensure accurate segmentation regardless of pathology. Agreement between manual and automated segmentations was assessed by degree of overlap (Dice coefficient) and comparison of hippocampal volumes. KEY FINDINGS: The automated segmentation algorithm provided robust delineation of the hippocampi on 3T scans with no more variability than that seen between different human raters (Dice coefficients: interrater 0.832, manual vs. automated 0.847). In addition, the algorithm provided excellent results with the 1.5T scans (Dice coefficient 0.827), and automated segmentation remained accurate even in small sclerotic hippocampi. There was a strong correlation between manual and automated hippocampal volumes (Pearson correlation coefficient 0.929 on the left and 0.941 on the right in 3T scans). SIGNIFICANCE: We demonstrate reliable identification of hippocampal atrophy in patients with hippocampal sclerosis, which is crucial for clinical management of epilepsy, particularly if surgical treatment is being contemplated. We provide a free online Web-based service to enable hippocampal volumetry to be available globally, with consequent greatly improved evaluation of those with epilepsy.

High-resolution diffusion tensor imaging of the hippocampus in temporal lobe epilepsy.

PURPOSE: To assess the quantitative diffusion characteristics of the hippocampus with high-resolution diffusion tensor imaging (DTI) in temporal lobe epilepsy (TLE). METHODS: Thirteen controls and seven unilateral TLE patients (six with hippocampal sclerosis, one with normal magnetic resonance imaging (MRI)) were scanned with DTI using a zonally magnified oblique multislice echo planar imaging (ZOOM-EPI) acquisition. Fractional anisotropy (FA) and mean diffusivity (MD) were measured in the hippocampi. RESULTS: The mean hippocampal MD ipsilateral to the seizure focus was higher than the contralateral MD in patients (p<0.05) and the mean MD in controls (p<0.001). Hippocampal FA ipsilateral to the seizure focus was lower than the mean FA in controls (p<0.05). MD asymmetry indexes were significantly different between the patient and control groups (p<0.01). All six individual HS patients had ipsilateral hippocampal MD >or=2 standard deviations (S.D.) above the control mean. The patient with normal structural MRI had bilaterally low hippocampal FA and high MD. DISCUSSION: High-resolution DTI identifies lateralizing abnormalities of MD and FA in TLE patients. This quantitative data on hippocampal integrity may assist in evaluating TLE patients with normal MRI, and in longitudinal studies.

The value of repeat neuroimaging for epilepsy at a tertiary referral centre: 16 years of experience.

PURPOSE: Magnetic resonance imaging (MRI) is the investigation of choice for detecting structural lesions that underlie and may accompany epilepsy. Despite advances in imaging technology, 20-30% of patients with refractory focal epilepsy have normal MRI scans. We evaluated the role of repeated imaging with improved MRI technology - an increase in field strength from 1.5T to 3T and superior head coils - in detecting pathology not previously seen. METHODS: Retrospective review of a large cohort of patients attending a tertiary epilepsy referral centre who underwent MRI at 1.5T (1995-2004) and subsequently 3T (2004-2011) with improved head coils. Scan reports were reviewed for the diagnoses and medical notes for the epilepsy classification. RESULTS: 804 patients underwent imaging on both scanners, the majority with focal epilepsy (87%). On repeat scanning at 3T, 37% of scans were normal and 20% showed incidental findings. Positive findings included hippocampal sclerosis (13%), malformations of cortical development (8%), other abnormalities (4%) and previous surgery (18%). A total of 37 (5%) relevant new diagnoses were made on the 3T scans not previously seen at 1.5T. The most common new findings were hippocampal sclerosis, focal cortical dysplasia and dysembryoplastic neuroepithelial tumour. These findings affected patient management with several patients undergoing neurosurgery. CONCLUSIONS: The higher field strength and improved head coils were associated with a clinically relevant increased diagnostic yield from MRI. This highlights the importance of technological advances and suggests that rescanning patients with focal epilepsy and previously negative scans is clinically beneficial.

Voxel-based diffusion tensor imaging in patients with mesial temporal lobe epilepsy and hippocampal sclerosis.

BACKGROUND: Mesial temporal lobe epilepsy (mTLE) with hippocampus sclerosis (HS) is an important cause for focal epilepsy. In this study, we explored the integrity of connecting networks using diffusion tensor imaging (DTI) and two whole-brain voxel-based methods: statistical parametric mapping (SPM) and tract-based spatial statistics (TBSS). METHODS: Thirty-three consecutive patients with mTLE and HS undergoing presurgical evaluation were scanned at 3 T, a DTI data set was acquired and parametric maps of fractional anisotropy (FA) and mean diffusivity (MD) were calculated. Twenty-one patients had left hippocampal sclerosis (LHS) and 12 patients had right HS (RHS). These groups were compared to 37 normal control subjects using both SPM5 and TBSS. RESULTS: The ipsilateral temporal lobe showed widespread FA reduction in both groups. The limbic system was clearly abnormal in the LHS group, also involving the arcuate fasciculus. In RHS, changes were more restricted but also showed involvement of the contralateral temporal and inferior frontal lobe. Increased MD was found in the ipsilateral hippocampus by SPM that was only marginally detected by TBSS. In white matter regions, however, TBSS was more sensitive to changes than SPM. CONCLUSION: DTI detects extensive changes in mTLE with HS. The affected networks were principally in the ipsilateral temporal lobe and the limbic system but also the arcuate fasciculus. SPM and TBSS gave complementary information with higher sensitivity to FA changes using TBSS.

PROPELLER MRI visualizes detailed pathology of hippocampal sclerosis.

PURPOSE: Hippocampal sclerosis (HS) is the most common cause of refractory temporal lobe epilepsy. Histopathologically, HS is characterized by neuron loss and gliosis. HS can be identified on MRI by signal increase on T(2)-weighted images and volume loss on T(1)-weighted volume images. The Periodically Rotated Overlapping Parallel Lines with Enhanced Reconstruction ("PROPELLER") sequence has excellent contrast between grey and white matter and compensates for subjects moving during the scan. The aim of the current report was to explore PROPELLER image quality of the hippocampus compared to routine sequences. METHODS: Routine sequences (T(1) volume, T(2)-weighted, PD and FLAIR images) and PROPELLER images were acquired in four presurgical patients with HS using a GE 3T Excite HD scanner (General Electric). Resected tissue was stained with LFB, and for GFAP, NeuN and dynorphin immunohistochemistry. Hippocampal sections were compared with PROPELLER images. RESULTS: PROPELLER images were T(2)-weighted and had superior tissue contrast compared to routine sequences. PROPELLER images showed the internal hippocampal structures and tissue changes associated with HS. This corresponded to changes seen on histopathological sections confirming that the sequence could distinguish between different strata and subfields of the hippocampus. DISCUSSION: The PROPELLER sequence shows promise for detailed in vivo imaging of the hippocampus in patients who did not move overtly, negating the inevitable subtle movements during scans. More detailed in vivo studies of the hippocampal formation, investigating subtle abnormalities such as end folium sclerosis, and the neocortex are now possible and may increase the diagnostic yield of MRI.

Cerebral damage in epilepsy: a population-based longitudinal quantitative MRI study.

PURPOSE: Whether cerebral damage results from epileptic seizures remains a contentious issue. We report on the first longitudinal community-based quantitative magnetic resonance imaging (MRI) study to investigate the effect of seizures on the hippocampus, cerebellum, and neocortex. METHODS: One hundred seventy-nine patients with epilepsy (66 temporal lobe epilepsy, 51 extratemporal partial epilepsy, and 62 generalized epilepsy) and 90 control subjects underwent two MRI brain scans 3.5 years apart. Automated and manual measurement techniques identified changes in global and regional brain volumes and hippocampal T2 relaxation times. RESULTS: Baseline hippocampal volumes were significantly reduced in patients with temporal lobe epilepsy and could be attributed to an antecedent neurologic insult. Rates of hippocampal, cerebral, and cerebellar atrophy were not syndrome specific and were similar in control and patient groups. Global and regional brain atrophy was determined primarily by age. A prior neurologic insult was associated with reduced hippocampal and cerebellar volumes and an increased rate of cerebellar atrophy. Significant atrophy of the hippocampus, neocortex, or cerebellum occurred in 17% of patients compared with 6.7% of control subjects. Patients with and without significant volume reduction were comparable in terms of seizure frequency, antiepileptic drug (AED) use, and epilepsy duration, with no identifiable risk factors for the development of atrophy. CONCLUSIONS: Overt structural cerebral damage is not an inevitable consequence of epileptic seizures. In general, brain volume reduction in epilepsy is the cumulative effect of an initial precipitating injury and age-related cerebral atrophy. Significant atrophy developed in individual patients, particularly those with temporal lobe and generalized epilepsy. Longer periods of observation may detect more subtle effects of seizures.

A short-echo-time proton magnetic resonance spectroscopic imaging study of temporal lobe epilepsy.

PURPOSE: We used short-echo-time proton magnetic resonance spectroscopy imaging (MRSI) to study metabolite concentration variation through the temporal lobe in patients with temporal lobe epilepsy (TLE) with and without abnormal MRI. METHODS: MRSI was performed at TE = 30 ms to study 10 control subjects, 10 patients with TLE and unilateral hippocampal sclerosis, and 10 patients with TLE and unremarkable MRI (MRI negative). We measured the concentrations of N-acetyl aspartate +N-acetyl aspartyl-glutamate (NAAt), creatine (Cr), choline (Cho), glutamate + glutamine (Glx), and myoinositol, in the anterior, middle, and posterior medial temporal lobe (MTL), and in the posterior lateral temporal lobe. Segmented volumetric T1-weighted MRIs gave the tissue composition of each MRSI voxel. Normal ranges were defined as the control mean +/- 3 SD. RESULTS: In the hippocampal sclerosis group, seven of 10 had abnormally low NAAt in the ipsilateral anterior MTL. In the MRI-negative group, four of 10 had low NAAt in the middle MTL voxel ipsilateral to seizure onset. Metabolite ratios were less sensitive to abnormality than was the NAAt concentration. Group analysis showed low NAAt, Cr, and Cho in the anterior MTL in hippocampal sclerosis. Glx was elevated in the anterior voxel contralateral to seizure onset in the MRI-negative group. Metabolite concentrations were influenced by voxel position and tissue composition. CONCLUSIONS: (a) Low NAAt, Cr, and Cho were features of the anterior sclerotic hippocampus, whereas low NAAt was observed in the MRI-negative group in the middle MTL region. The posterior temporal lobe regions were not associated with significant metabolite abnormality; (b) The two patient groups demonstrated different metabolite profiles across the temporal lobe, with elevated Glx a feature of the MRI-negative group; and (c) Voxel tissue composition and position influenced obtained metabolite concentrations.

Progressive neocortical damage in epilepsy.

Our objective was to determine the pattern and extent of generalized and focal neocortical atrophy that develops in patients with epilepsy and the factors associated with such changes. As part of a prospective, longitudinal follow-up study of 122 patients with chronic epilepsy, 68 newly diagnosed patients, and 90 controls, serial magnetic resonance imaging scans were obtained 3.5 years apart. Image subtraction was used to identify diffuse and focal neocortical change that was quantified with a regional brain atlas and a fully automated segmentation algorithm. New focal or generalized neocortical volume losses were identified in 54% of patients with chronic epilepsy, 39% of newly diagnosed patients and 24% of controls. Patients with chronic epilepsy were significantly more likely to develop neocortical atrophy than control subjects. The increased risk of cerebral atrophy in epilepsy was not related to a history of documented seizures. Risk factors for neocortical atrophy were age and multiple antiepileptic drug exposure. Focal and generalized neocortical atrophy commonly develops in chronic epilepsy. Neocortical changes seen in a quarter of our control group over 3.5 years were likely to reflect physiological changes. Our results show that ongoing cerebral atrophy may be widespread and remote from the putative epileptic focus, possibly reflecting extensive networks and interconnections between cortical regions.

The structural consequences of newly diagnosed seizures.

Intractable epilepsy may be associated with widespread structural cerebral damage. We determined whether structural damage occurs to the hippocampus, cerebellum and neocortex in the first few years following a diagnosis of seizures. Sixty-eight patients over the age of 14 years with newly diagnosed seizures and 90 matched controls underwent serial magnetic resonance imaging (MRI) brain scans 3.5 years apart. Using quantitative analysis of serial scans, we determined changes in hippocampal volume, hippocampal T2 relaxometry and total and regional brain volumes. Thirty-four (50%) patients had recurrent unprovoked seizures between baseline and follow-up scans. One patient with pre-existing hippocampal sclerosis (HS) did not develop progressive hippocampal damage. Group analyses found no difference in change in cerebral measures between patients and controls or between patients with and without recurrent seizures. Significant quantitative changes in individuals were largely attributable to pre-existing cerebral lesions or alcohol abuse. Subtle changes detected in individuals over 3.5 years but were not related to a history of overt seizures. Our results show patients with newly diagnosed seizures are not generally at increased risk of seizure-induced structural cerebral damage as detected with MRI. Cerebral damage may occur before the onset of seizures or develop insidiously over a more prolonged period.