Statistical asymmetry analysis of volumetric MRI and FDG PET in temporal lobe epilepsy.

PURPOSE: To analyze statistically derived threshold values of volumetric MRI and 18F fluorodeoxyglucose (FDG) PET asymmetry, independent of normative data, for non-invasive detection/exclusion of temporal lobe epilepsy (TLE). METHODS: We retrospectively analyzed amygdalohippocampal volumetry and temporal FDG PET metabolism in 33 patients (age: 29.27 ±â€¯8.56 years) who underwent surgery following Stereo-EEG implantation and had postsurgical seizure freedom lasting >12 months. The temporal lobe epilepsy group and the extratemporal lobe epilepsy (ETLE) group were compared. Percentage volume loss (PVL) was calculated from manually traced amygdalohippocampal volumetry whereas percentage metabolic loss (PML) was calculated from PET using amygdalohippocampal trace and temporal neocortical Brodmann areas (BA) template. RESULTS: Receiver operating characteristic (ROC) curve analysis identified a cutoff hippocampal PVL of 4.21% as the minimum indicating probable hippocampal involvement in seizure onset, with sensitivity of 88.89% and the specificity of 100% (p < 0.001). Region of interest (ROI)-based PML values in PET imaging showed a significant correlation with the presence of TLE in the TLE group of patients and its absence in the ETLE group of patients. Region of interest curve analysis yielded PML cutoffs of 5.77% and 8.36%, respectively, for the hippocampus and BA 38 (temporopolar neocortex) to detect TLE with the sensitivity of 72.7% and specificity of 77.8%. CONCLUSION: We describe statistical thresholds for asymmetry analysis of hippocampal volumetry and FDG PET to improve detection of TLE. These threshold parameters warrant further validation in prospective studies.

Diagnostic performance of hippocampal volumetry in Alzheimer's disease or mild cognitive impairment: a meta-analysis.

OBJECTIVE: To evaluate the diagnostic performance of hippocampal volumetry for Alzheimer's disease (AD) or mild cognitive impairment (MCI). METHODS: The MEDLINE and Embase databases were searched for articles that evaluated the diagnostic performance of hippocampal volumetry in differentiating AD or MCI from normal controls, published up to March 6, 2022. The quality of the articles was evaluated by the QUADAS-2 tool. A bivariate random-effects model was used to pool sensitivity, specificity, and area under the curve. Sensitivity analysis and meta-regression were conducted to explain study heterogeneity. The diagnostic performance of entorhinal cortex volumetry was also pooled. RESULTS: Thirty-three articles (5157 patients) were included. The pooled sensitivity and specificity for AD were 82% (95% confidence interval [CI], 77-86%) and 87% (95% CI, 82-91%), whereas those for MCI were 60% (95% CI, 51-69%) and 75% (95% CI, 67-81%), respectively. No difference in the diagnostic performance was observed between automatic and manual segmentation (p = 0.11). MMSE scores, study design, and the reference standard being used were associated with study heterogeneity (p < 0.01). Subgroup analysis demonstrated a higher diagnostic performance of entorhinal cortex volumetry for both AD (pooled sensitivity: 88% vs. 79%, specificity: 92% vs. 89%, p = 0.07) and MCI (pooled sensitivity: 71% vs. 55%, specificity: 83% vs. 68%, p = 0.06). CONCLUSIONS: Our meta-analysis demonstrated good diagnostic performance of hippocampal volumetry for AD or MCI. Entorhinal cortex volumetry might have superior diagnostic performance to hippocampal volumetry. However, due to a small number of studies, the diagnostic performance of entorhinal cortex volumetry is yet to be determined. KEY POINTS: • The pooled sensitivity and specificity of hippocampal volumetry for Alzheimer's disease were 82% and 87%, whereas those for mild cognitive impairment were 60% and 75%, respectively. • No significant difference in the diagnostic performance was observed between automatic and manual segmentation. • Subgroup analysis demonstrated superior diagnostic performance of entorhinal cortex volumetry for AD (pooled sensitivity: 88%, specificity: 92%) and MCI (pooled sensitivity: 71%, specificity: 83%).

Histopathological validation and clinical correlates of hippocampal subfield volumetry based on T2-weighted MRI in temporal lobe epilepsy with hippocampal sclerosis.

The objectives of this study were 1) to histologically validate the hippocampal subfield volumetry based on T2-weighted MRI, and 2) to explore its clinical impact on postsurgical memory function and seizure outcome in temporal lobe epilepsy (TLE) with hippocampal sclerosis (HS). We analyzed the cases of 24 patients with medial TLE (12 left, 12 right) and HS who were preoperatively examined with T2-weighted high-resolution MRI. The volume of each hippocampal subfield was calculated with an automatic segmentation of hippocampal subfields (ASHS) program. Hippocampal sclerosis patterns were determined pathologically, and the cross-sectional area and neuronal cell density of the CA1 and CA4 subfields were calculated using tissue specimens. Pre- and postoperative memory evaluations based on the Wechsler Memory Scale-Revised (WMS-R) were performed. We compared the presurgical MRI-based volumes with the pathological measurements in each subfield and then compared them with the change in the patients' neurocognitive function. As a result, there was a significant relationship between the presurgical MRI-based volume of CA4/dentate gyrus (DG) and the cross-sectional area of CA4 calculated with tissue specimens (Spearman's rs = 0.482, p = 0.023), and a similar trend-level correlation was observed in CA1 (rs = 0.455, p = 0.058). Some of MRI-based or pathology-based parameters in the subfields preliminarily showed relationships with the postsurgical memory changes. In conclusion, automated subfield volumetry for patients with hippocampal sclerosis moderately reflects their subfield atrophy and might be useful to predict the postsurgical change of memory function in these patients.

Relationship between hippocampal subfields and Verbal and Visual memory function in Mesial Temporal Lobe Epilepsy patients.

OBJECTIVE: High-resolution protocols used in magnetic resonance imaging (MRI) currently enable the detailed analysis of the hippocampus along with its subfield segmentation. The relationship between episodic memory and the hippocampus is well established, and there is growing evidence that some specific memory processing steps are associated with individual hippocampal segments, but there are inconsistencies in the literature. We focused our analysis on hippocampal subfield volumetry and neuropsychological visual and verbal memory tests in patients with temporal lobe epilepsy (TLE) presenting with unilateral hippocampal atrophy. METHODS: The study involved a cohort of 62 patients with unilateral TLE, including unilateral hippocampal atrophy (29 on the left side) based on MRI and unequivocal ipsilateral ictal onsets based on surface video electroencephalography recordings. The hippocampal subfield volumes were evaluated using FreeSurfer version 7.1. We used the Rey-Auditory Verbal Learning Test to evaluate short-term (A1), learning (ΣA1-A5), immediate (A6), and delayed (A7) recall of episodic verbal memory. We used the Rey-Osterrieth Complex Figure Test to evaluate the immediate and delayed recall of visual memory. We analyzed the correlations between the asymmetry index scores for the hippocampal subfield volumes of thecornu ammonis (CA)1, CA2/3, and CA4 and memory test performance. RESULTS: Moderate associations were established between the CA2/3 asymmetry index scores and visual memory in TLE (both right and left hippocampal atrophy), as well as visual memory and CA4 in the right atrophy cases. The CA1 asymmetry index scores did not correlate with any of the memory test results. We did not find any significant correlation between verbal memory tests and specific hippocampal subfields. CONCLUSIONS: The use of high-resolution MRI protocols andin vivo automated segmentation processing revealed moderate associations between hippocampal subfields and memory parameters. Further investigations are needed to establish the utility of these results for clinical decisions.

Are HFOs in the Intra-operative ECoG Related to Hippocampal Sclerosis, Volume and IQ?

Temporal lobe epilepsy (TLE) is the most common form of refractory focal epilepsy and is often associated with hippocampal sclerosis (HS) and cognitive disturbances. Over the last decade, high frequency oscillations (HFOs) in the intraoperative electrocorticography (ioECoG) have been proposed to be biomarkers for the delineation of epileptic tissue but hippocampal ripples have also been associated with memory consolidation. Healthy hippocampi can show prolonged ripple activity in stereo- EEG. We aimed to identify how the HFO rates [ripples (80-250 Hz, fast ripples (250-500 Hz); prolonged ripples (80-250 Hz, 200-500 ms)] in the pre-resection ioECoG over subtemporal area (hippocampus) and lateral temporal neocortex relate to presence of hippocampal sclerosis, the hippocampal volume quantified on MRI and the severity of cognitive impairment in TLE patients. Volumetric measurement of hippocampal subregions was performed in 47 patients with TLE, who underwent ioECoG. Ripples, prolonged ripples, and fast ripples were visually marked and rates of HFOs were calculated. The intellectual quotient (IQ) before resection was determined. There was a trend toward higher rates of ripples and fast ripples in subtemporal electrodes vs. the lateral neocortex (ripples: 2.1 vs. 1.3/min; fast ripples: 0.9 vs. 0.2/min). Patients with HS showed higher rates of subtemporal fast ripples than other patients (Z = -2.51, p = 0.012). Prolonged ripples were only found in the lateral temporal neocortex. The normalized ratio (smallest/largest) of hippocampal volume was correlated to pre-resection IQ (r = 0.45, p = 0.015). There was no correlation between HFO rates and hippocampal volumes or HFO rates and IQ. To conclude, intra-operative fast ripples were a marker for HS, but ripples and fast ripples were not linearly correlated with either the amount of hippocampal atrophy, nor for pre-surgical IQ.

Comparative analysis of methods of volume adjustment in hippocampal volumetry for the diagnosis of Alzheimer disease.

INTRODUCTION: Hippocampal volumetry can discriminate normal subjects from patients with amnestic mild cognitive impairment (MCI) or Alzheimer disease (AD). We have analyzed the effects of different methods of hippocampal volume (HV) adjustment on the diagnostic accuracy of this technique. METHODS: Cross-sectional analysis of 148 subjects of the ADNI database (48 normal, 66 MCI, 34 AD). Brain volumes were calculated from 3T MRI scans with gm extractor, a fully automated script based on FSL. A series of logistic regression models was obtained using 9 volumes of reference and 3 methods of adjustment (normalization, covariance, bilinear regression). Diagnostic accuracy was evaluated with the receiver operating characteristic curve method. External validity was assessed with 10-fold cross-validation. RESULTS: The models with the highest area under the curve (AUC) were those including the HV normalized by total intracranial volume (TIV). The differences with bilinear regression and the covariance method adjusted by TIV were minor and not statistically significant. The lowest AUCs corresponded to the models based on raw (unadjusted) HVs. The results were qualitatively similar in two clinical settings (normal versus MCI, and normal versus AD), but the differences were higher in the normal versus MCI context. CONCLUSION: The accuracy of hippocampal volumetry for the differential diagnosis between normal subjects and patients with MCI or AD was maximized by normalizing the HV by the TIV. Our results do not exclude the potential superiority of non-linear models.

Hippocampal profiling: Localized magnetic resonance imaging volumetry and T2 relaxometry for hippocampal sclerosis.

OBJECTIVE: Hippocampal sclerosis (HS) is the most common cause of drug-resistant temporal lobe epilepsy, and its accurate detection is important to guide epilepsy surgery. Radiological features of HS include hippocampal volume loss and increased T2 signal, which can both be quantified to help improve detection. In this work, we extend these quantitative methods to generate cross-sectional area and T2 profiles along the hippocampal long axis to improve the localization of hippocampal abnormalities. METHODS: T1-weighted and T2 relaxometry data from 69 HS patients (32 left, 32 right, 5 bilateral) and 111 healthy controls were acquired on a 3-T magnetic resonance imaging (MRI) scanner. Automated hippocampal segmentation and T2 relaxometry were performed and used to calculate whole-hippocampal volumes and to estimate quantitative T2 (qT2) values. By generating a group template from the controls, and aligning this so that the hippocampal long axes were along the anterior-posterior axis, we were able to calculate hippocampal cross-sectional area and qT2 by a slicewise method to localize any volume loss or T2 hyperintensity. Individual patient profiles were compared with normative data generated from the healthy controls. RESULTS: Profiling of hippocampal volumetric and qT2 data could be performed automatically and reproducibly. HS patients commonly showed widespread decreases in volume and increases in T2 along the length of the affected hippocampus, and focal changes may also be identified. Patterns of atrophy and T2 increase in the left hippocampus were similar between left, right, and bilateral HS. These profiles have potential to distinguish between sclerosis affecting volume and qT2 in the whole or parts of the hippocampus, and may aid the radiological diagnosis in uncertain cases or cases with subtle or focal abnormalities where standard whole-hippocampal measurements yield normal values. SIGNIFICANCE: Hippocampal profiling of volumetry and qT2 values can help spatially localize hippocampal MRI abnormalities and work toward improved sensitivity of subtle focal lesions.

Hippocampal volumetric integrity in mesial temporal lobe epilepsy: A fast novel method for analysis of structural MRI.

OBJECTIVE: We investigate whether a rapid and novel automated MRI processing technique for assessing hippocampal volumetric integrity (HVI) can be used to identify hippocampal sclerosis (HS) in patients with mesial temporal lobe epilepsy (mTLE) and determine its performance relative to hippocampal volumetry (HV) and visual inspection. METHODS: We applied the HVI technique to T1-weighted brain images from healthy control (n = 35), mTLE (n = 29), non-HS temporal lobe epilepsy (TLE, n = 44), and extratemporal focal epilepsy (EXTLE, n = 25) subjects imaged using a standardized epilepsy research imaging protocol and on non-standardized clinically acquired images from mTLE subjects (n = 40) to investigate if the technique is translatable to clinical practice. Performance of HVI, HV, and visual inspection was assessed using receiver operating characteristic (ROC) analysis. RESULTS: mTLE patients from both research and clinical groups had significantly reduced ipsilateral HVI relative to controls (effect size: -0.053, 5.62%, p =  0.002 using a standardized research imaging protocol). For lateralizing mTLE, HVI had a sensitivity of 88% compared with a HV sensitivity of 92% when using specificity equal to 70%. CONCLUSIONS: The novel HVI approach can effectively detect HS in clinical populations, with an average image processing time of less than a minute. The fast processing speed suggests this technique could have utility as a quantitative tool to assist with imaging-based diagnosis and lateralization of HS in a clinical setting.

Long-term outcome and neuroradiologic changes after multiple hippocampal transection combined with multiple subpial transection or lesionectomy for temporal lobe epilepsy.

OBJECTIVE: Multiple hippocampal transection (MHT) is a surgical procedure developed to avoid postoperative memory decline. Its efficacy has been documented in only a few small series with relatively short observation periods. We prospectively evaluated the long-term seizure and cognitive outcomes of MHT combined with multiple subpial transection or lesionectomy (MHT + MST/L). Moreover, we quantitatively evaluated the structural and metabolic neuroradiologic changes after the procedure to elucidate the anatomofunctional correlates of memory preservation. METHODS: Twenty-four patients underwent MHT + MST/L for treatment of drug-resistant mesial temporal lobe epilepsy (mTLE) and were followed for more than 5 years. Indications for the procedure were the following: (1) verbally dominant-sided surgery in patients with a radiologically normal hippocampus or normal/near normal memory, and (2) surgery for patients with concomitant epileptic activity on the contralateral side, that is, when the surgery was considered a high risk for severe postoperative memory decline. Seizure outcome was evaluated using Engel's classification 1, 2, and 3 years after surgery, and at the last visit (LV). Three subgroups were evaluated as well: magnetic resonance imaging (MRI) negative (MN), hippocampal sclerosis (HS), and normal hippocampus with extrahippocampal lesion (NHEL). The long-term cognitive outcome was followed through to LV in patients who underwent verbally dominant-sided surgery. Hippocampal volume (HV), diffusion tensor parameters (DTP), and glucose utilization (GU) were determined from MRI and fluorodeoxyglucose-positron emission tomography (FDG-PET) studies performed before and >6 months after surgery. RESULTS: Whereas the rate of Engel class I as a whole was 71% at 1 year and 67% at LV, the rates in the MN, HS, and NHEL groups were 60%, 67%, and 100% at 1 year, respectively, and 70%, 56%, and 80% at LV, respectively. Memory indices after verbally dominant-sided surgery transiently declined at 1 month but recovered to and remained at the preoperative level through LV. The HV, DTP of the fornix, and GU of the temporal lobe on the treated side showed pathologic changes even when the transiently declined memory indices had recovered to the preoperative level. SIGNIFICANCE: The long-term outcome for complex partial seizures after MHT + MST/L was comparable to that seen after anterior temporal lobectomy. The long-term cognitive outcome was favorable, even for patients with a high risk of severe postoperative memory decline. MHT + MST/L may be a treatment option for mTLE in which resective surgery carries a risk of postoperative memory decline, particularly in patients without MRI lesion. A discrepancy between the preserved memory and the pathologic neuroradiologic changes indicates the necessity for further studies including functional MRI.

Performance of Hippocampus Volumetry with FSL-FIRST for Prediction of Alzheimer's Disease Dementia in at Risk Subjects with Amnestic Mild Cognitive Impairment.

MRI-based hippocampus volume, a core feasible biomarker of Alzheimer's disease (AD), is not yet widely used in clinical patient care, partly due to lack of validation of software tools for hippocampal volumetry that are compatible with routine workflow. Here, we evaluate fully-automated and computationally efficient hippocampal volumetry with FSL-FIRST for prediction of AD dementia (ADD) in subjects with amnestic mild cognitive impairment (aMCI) from phase 1 of the Alzheimer's Disease Neuroimaging Initiative. Receiver operating characteristic analysis of FSL-FIRST hippocampal volume (corrected for head size and age) revealed an area under the curve of 0.79, 0.70, and 0.70 for prediction of aMCI-to-ADD conversion within 12, 24, or 36 months, respectively. Thus, FSL-FIRST provides about the same power for prediction of progression to ADD in aMCI as other volumetry methods.

No difference in paired associative stimulation induced cortical neuroplasticity between patients with mild cognitive impairment and elderly controls.

OBJECTIVE: Paired associative stimulation (PAS) is a widely used transcranial magnetic stimulation (TMS) paradigm to induce synaptic long-term potentiation (LTP)-like plasticity in the intact human brain. The PAS effect is reduced in Alzheimer's dementia (AD) but has not yet been assessed in patients with mild cognitive impairment (MCI). METHODS: PAS was assessed in a group of 24 MCI patients and 24 elderly controls. MCI patients were further stratified by their cognitive profile as well as hippocampal atrophy and Apolipoprotein E (ApoE) genotype. RESULTS: There was no difference in PAS effects between MCI patients and healthy controls. MCI patients tended to show a higher response rate and an average PAS effect. PAS effects were not correlated with markers of disease severity or ApoE genotype but were more pronounced in individuals with shorter sleep duration and in MCI subjects with higher ratings of subjective alertness. CONCLUSIONS: Contrary to our initial hypothesis, there was no clear difference in PAS between MCI patients and healthy controls. SIGNIFICANCE: Our results argue against a continuous reduction of LTP-like plasticity along the spectrum of clinical MCI when stratified by MCI-subtype, APOE genotype or hippocampus atrophy.

Temporal lobe epilepsy patients with severe hippocampal neuron loss but normal hippocampal volume: Extracellular matrix molecules are important for the maintenance of hippocampal volume.

OBJECTIVE: Hippocampal sclerosis is a common finding in patients with temporal lobe epilepsy (TLE), and magnetic resonance imaging (MRI) studies associate the reduction of hippocampal volume with the neuron loss seen on histologic evaluation. Astrogliosis and increased levels of chondroitin sulfate, a major component of brain extracellular matrix, are also seen in hippocampal sclerosis. Our aim was to evaluate the association between hippocampal volume and chondroitin sulfate, as well as neuronal and astroglial populations in the hippocampus of patients with TLE. METHODS: Patients with drug-resistant TLE were subdivided, according to hippocampal volume measured by MRI, into two groups: hippocampal atrophy (HA) or normal volume (NV) cases. Hippocampi from TLE patients and age-matched controls were submitted to immunohistochemistry to evaluate neuronal population, astroglial population, and chondroitin sulfate expression with antibodies against neuron nuclei protein (NeuN), glial fibrillary acidic protein (GFAP), and chondroitin sulfate (CS-56) antigens, respectively. RESULTS: Both TLE groups were clinically similar. NV cases had higher hippocampal volume, both ipsilateral and contralateral, when compared to HA. Compared to controls, NV and HA patients had reduced neuron density, and increased GFAP and CS-56 immunopositive area. There was no statistical difference between NV and HA groups in neuron density or immunopositive areas for GFAP and CS-56. Hippocampal volume correlated positively with neuron density in CA1 and prosubiculum, and with immunopositive areas for CS-56 in CA1, and negatively with immunopositive area for GFAP in CA1. Multiple linear regression analysis indicated that both neuron density and CS-56 immunopositive area in CA1 were statistically significant predictors of hippocampal volume. SIGNIFICANCE: Our findings indicate that neuron density and chondroitin sulfate immunopositive area in the CA1 subfield are crucial for the hippocampal volume, and that chondroitin sulfate is important for the maintenance of a normal hippocampal volume in some cases with severe neuron loss.

Fully automated atlas-based hippocampal volumetry for detection of Alzheimer's disease in a memory clinic setting.

Hippocampal volume is a promising biomarker to enhance the accuracy of the diagnosis of dementia due to Alzheimer's disease (AD). However, whereas hippocampal volume is well studied in patient samples from clinical trials, its value in clinical routine patient care is still rather unclear. The aim of the present study, therefore, was to evaluate fully automated atlas-based hippocampal volumetry for detection of AD in the setting of a secondary care expert memory clinic for outpatients. One-hundred consecutive patients with memory complaints were clinically evaluated and categorized into three diagnostic groups: AD, intermediate AD, and non-AD. A software tool based on open source software (Statistical Parametric Mapping SPM8) was employed for fully automated tissue segmentation and stereotactical normalization of high-resolution three-dimensional T1-weighted magnetic resonance images. Predefined standard masks were used for computation of grey matter volume of the left and right hippocampus which then was scaled to the patient's total grey matter volume. The right hippocampal volume provided an area under the receiver operating characteristic curve of 84% for detection of AD patients in the whole sample. This indicates that fully automated MR-based hippocampal volumetry fulfills the requirements for a relevant core feasible biomarker for detection of AD in everyday patient care in a secondary care memory clinic for outpatients. The software used in the present study has been made freely available as an SPM8 toolbox. It is robust and fast so that it is easily integrated into routine workflow.

Volumetric analysis of hippocampal sub-regions in late onset depression: a 3 tesla magnetic resonance imaging study.

BACKGROUND: While many studies have reported reduced volume of hippocampus in late onset depression (LOD), the status of hippocampus sub-regions (anterior/posterior) is yet to be explored. Evaluating hippocampal sub-regions might facilitate better elucidation of the neurobiological basis of LOD. METHODS: Twenty five elderly subjects with LOD (mean age=65.28yr, SD=5.73, 15 females) and 20 healthy controls (mean age=65.35yr, SD=5.67, 7 females) were examined using 3-tesla magnetic resonance imaging (MRI). They were also evaluated with Montgomery Asberg Depression Rating Scale (MADRS) and Hindi Mental State Examination (HMSE). We examined the difference in volume of Hippocampal sub-regions between the LOD group and control group controlling for the age, sex and intracranial volume. RESULTS: Left posterior hippocampus volume was significantly smaller in LOD group than the control group (1.01±0.19ml vs 1.16±0.25ml, F=7.50, p=0.009). There was a similar trend for the right posterior hippocampus (1.08±0.19ml vs 1.18±0.27ml, F=3.18, p=0.082). Depression severity (mean MADRS score=20.64±8.99) had a significant negative correlation with volumes of right posterior hippocampus (r=-0.37, p=0.012) and left posterior hippocampus (r=-0.46, p=0.001) in the LOD group. CONCLUSIONS: Specific reduction of posterior hippocampus volume and its relationship with depression severity indicates sub region specific hippocampal volumetric abnormalities in LOD. Future studies need to evaluate sub region specific hippocampal volume in LOD longitudinally for better understanding of the pathogenesis of LOD in view of the functional differences between anterior and posterior hippocampus.

Operationalizing protocol differences for EADC-ADNI manual hippocampal segmentation.

BACKGROUND: Hippocampal volumetry on magnetic resonance imaging is recognized as an Alzheimer's disease (AD) biomarker, and manual segmentation is the gold standard for measurement. However, a standard procedure is lacking. We operationalize and quantitate landmark differences to help a Delphi panel converge on a set of landmarks. METHODS: One hundred percent of anatomic landmark variability across 12 different protocols for manual segmentation was reduced into four segmentation units (the minimum hippocampus, the alveus/fimbria, the tail, and the subiculum), which were segmented on magnetic resonance images by expert raters to estimate reliability and AD-related atrophy. RESULTS: Intra- and interrater reliability were more than 0.96 and 0.92, respectively, except for the alveus/fimbria, which were 0.86 and 0.77, respectively. Of all AD-related atrophy, the minimum hippocampus contributed to 67%; tail, 24%; alveus/fimbria, 4%; and the subiculum, 5%. CONCLUSIONS: Anatomic landmark variability in available protocols can be reduced to four discrete and measurable segmentation units. Their quantitative assessment will help a Delphi panel to define a set of landmarks for a harmonized protocol.

The EADC-ADNI Harmonized Protocol for manual hippocampal segmentation on magnetic resonance: evidence of validity.

BACKGROUND: An international Delphi panel has defined a harmonized protocol (HarP) for the manual segmentation of the hippocampus on MR. The aim of this study is to study the concurrent validity of the HarP toward local protocols, and its major sources of variance. METHODS: Fourteen tracers segmented 10 Alzheimer's Disease Neuroimaging Initiative (ADNI) cases scanned at 1.5 T and 3T following local protocols, qualified for segmentation based on the HarP through a standard web-platform and resegmented following the HarP. The five most accurate tracers followed the HarP to segment 15 ADNI cases acquired at three time points on both 1.5 T and 3T. RESULTS: The agreement among tracers was relatively low with the local protocols (absolute left/right ICC 0.44/0.43) and much higher with the HarP (absolute left/right ICC 0.88/0.89). On the larger set of 15 cases, the HarP agreement within (left/right ICC range: 0.94/0.95 to 0.99/0.99) and among tracers (left/right ICC range: 0.89/0.90) was very high. The volume variance due to different tracers was 0.9% of the total, comparing favorably to variance due to scanner manufacturer (1.2), atrophy rates (3.5), hemispheric asymmetry (3.7), field strength (4.4), and significantly smaller than the variance due to atrophy (33.5%, P < .001), and physiological variability (49.2%, P < .001). CONCLUSIONS: The HarP has high measurement stability compared with local segmentation protocols, and good reproducibility within and among human tracers. Hippocampi segmented with the HarP can be used as a reference for the qualification of human tracers and automated segmentation algorithms.

Magnetic resonance volumetry of the hippocampus in familial spontaneous epileptic cats.

A strain of familial spontaneous epileptic cats (FSECs) with typical limbic seizures was identified in 2010. The electroencephalographic features suggested that an epileptogenic zone is present in the mesial temporal structures (i.e., amygdala and/or hippocampus). In this study, visual evaluations and quantitative analyses were performed by using 3D MR hippocampal volumetry in comparing FSECs with age-matched controls. Visual hippocampal asymmetries were seen in 8 of 14 (57.1%) FSECs. The FSEC group showed a significantly higher asymmetric ratio (4.15%) than the control group (0.99%). The smaller side of hippocampal volume (HV) (0.206 cm(3)) in FSECs was significantly smaller than the mean HV in controls (0.227 cm(3)). However, the means of left and right HVs and total HVs in FSECs showed no differences because the laterality of hippocampal atrophy was different in each individual. Therefore, since FSECs represent a true model of spontaneous epilepsy, hippocampal volumetry should be evaluated in each individual as well as in human patients. The significant asymmetry of HV suggests the potential for hippocampal atrophy in FSECs.

Hippocampal volumetry: Normative data in the Indian population.

BACKGROUND: Mesial temporal sclerosis (MTS) is the most common cause of temporal lobe epilepsy. Quantitative analysis of the hippocampus using volumetry is commonly being used in the diagnosis of MTS and is being used as a marker in prognostication of seizure control. Although normative data for hippocampal volume (HV) is available for the western population, no such data is available for the Indian population. AIM: The aim of the study was to establish normative data for HV for the Indian population, which can aid in the accurate diagnosis of MTS. MATERIALS AND METHODS: Magnetic resonance imaging (MRI) scans of 200 healthy volunteers were acquired using a 3 Tesla (3T) MRI scanner. Manual segmentation and volumetry was done using Siemens Syngo software. The data was analyzed using two tailed t-test to detect associations between HV and age, gender, and education. The data so obtained was also correlated with the data available from the rest of the world. RESULTS: A mean HV of 2.411 cm(3) (standard deviation -0.299) was found in the study, which was significantly smaller when compared to the data from the western population. The right hippocampus was larger than the left, with a mean volume of 2.424 cm(3) and 2.398 cm(3), respectively. HV was detected to be significantly higher in males. No association was found between HV and age and education. CONCLUSION: The values obtained in this study may be adopted as a standard in the evaluation of patients with intractable epilepsy.

Combination of MRI hippocampal volumetry and arterial spin labeling MR perfusion at 3-Tesla improves the efficacy in discriminating Alzheimer's disease from cognitively normal elderly adults.

BACKGROUND: Structural magnetic resonance imaging has been employed for evaluation of medial temporal atrophy in patients with Alzheimer's disease (AD). Arterial spin labeling (ASL) technique could detect cerebral perfusion abnormalities in AD. OBJECTIVE: We hypothesized that combination of hippocampal volumetry and cerebral blood flow yield higher accuracy than either method alone in discriminating AD patients from cognitively normal elderly adults. MATERIALS AND METHODS: 13 AD patients and 15 healthy controls were studied using a 3-tesla scanner. Standardized T1W 3D volumetric Fast Field Echo and QUASAR ASL sequences were employed for cerebral volumetry and perfusion respectively. Manual Right and left hippocampal volumetry was performed manually by ANALYZE software, with total intracranial volume normalization. ASL data were analyzed by institutional specially-design software to calculate cerebral blood flow of region-of-interests placed at the middle and posterior cingulate gyri. RESULTS: Right and left hippocampal volumes and middle and posterior cingulate gyri cerebral blood flows were significantly lower in the patients than in the controls (independent-samples t-tests, p < 0.05), and prediction accuracies of 89.3%, 82.1%, 75.0% and 71.4% were achieved for each of the above parameters, respectively. In distinguishing patients from controls using corresponding optimized cut-off values, various combinations of these parameters were used to create the Receiver Operating Characteristic curves. The highest area under curve value was 0.944, by combining cerebral blood flow at the middle cingulate gyrus, normalized right and left hippocampal volumes. CONCLUSIONS: A 'one-stop-shop' magnetic resonance study of combined hippocampal volumetry and cerebral perfusion has improved efficacy in discriminating AD patients from cognitively normal elderly adults.