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de Souza L.C.,University Pierre and Marie Curie | de Souza L.C.,French Institute of Health and Medical Research | de Souza L.C.,French National Center for Scientific Research | de Souza L.C.,Alzheimer Institute | And 24 more authors.
Neurobiology of Aging | Year: 2012

Hippocampal atrophy as assessed by magnetic resonance imaging (MRI) and abnormal cerebrospinal fluid (CSF) biomarkers are supportive features for the diagnosis of Alzheimer's disease (AD) and are assumed to be indirect pathological markers of the disease. In AD patients, antemortem MRI hippocampal volumes (HVs) correlate with the density of neurofibrillary tangles (but not with senile plaques) at autopsy suggesting that HVs may better correlate with CSF tau and hyperphosphorylated tau (P-tau) levels than CSF amyloid beta protein (Aβ)42 level. Here, we tested this hypothesis in a well-defined AD group. Patients were selected according to the New Research Criteria for AD, including specific episodic memory deficit and CSF AD profile (defined as abnormal ratio of Aβ42:tau). MRI was performed within 6 months of lumbar puncture. HVs were obtained using automated segmentation software. Thirty-six patients were included. Left HV correlated with CSF tau (R = -0.53) and P-tau (R = -0.56) levels. Mean HVs correlated with the CSF P-tau level (R = -0.52). No correlation was found between any brain measurement and CSF Aβ42 level. The CSF tau and P-tau levels, but not the CSF Aβ42 level, correlated with HV, suggesting that CSF tau markers reflect the neuronal loss associated with the physiopathological process of AD. © 2012 Elsevier Inc.

Henry T.R.,University of Minnesota | Chupin M.,University Pierre and Marie Curie | Lehericy S.,University Pierre and Marie Curie | Lehericy S.,Center for Neuroimaging Research | And 5 more authors.
Radiology | Year: 2011

Purpose: To determine if ultrahigh-field-strength magnetic resonance (MR) imaging can be used to detect subregional hippocampal alterations. Materials and Methods: Subjects provided written consent to participate in this prospective institutional review board-approved HIPAA-compliant study. T1- and T2-weighted 7-T brain MR images were acquired in 11 healthy subjects and eight patients with temporal lobe epilepsy (TLE). In all subjects, images were qualitatively examined for evidence of hippocampal atrophy, signal change, and malrotation with the Bernasconi definition, and digitations of the hippocampal heads were counted (agreement was measured with the κ statistic). Data were analyzed quantitatively with manual subregional hippocampal body segmentation. Subregional data in individual subjects with TLE were compared with data in control subjects to detect deviation from the control range for volume measures on each side and with asymmetry indexes. Results: All eight patients with TLE had hippocampal abnormalities on the epileptogenic side. Subregional analysis revealed selective lateral Ammon horn atrophy in six patients and diffuse Ammon horn and dentate gyrus atrophy in one patient. Paucity of hippocampal digitations occurred on the epileptogenic side in all patients with TLE and also on the contralateral side in three patients (interrater κ value, 0.80). Hippocampal malrotation was observed in three patients with TLE and four control subjects. Conclusion: Ultrahigh-field-strength MR imaging permitted detection of selectively greater Ammon horn atrophy in patients with TLE and hippocampal sclerosis. Paucity of digitations is a deformity of the hippocampal head that was detected independent of hippocampal atrophy in patients with mesial TLE. © RSNA, 2011.

Yao B.,U.S. National Institutes of Health | Yao B.,Center for Neuroimaging Research | Hametner S.,Medical University of Vienna | Van Gelderen P.,U.S. National Institutes of Health | And 6 more authors.
PLoS ONE | Year: 2014

Background: Neocortical lesions (NLs) are an important pathological component of multiple sclerosis (MS), but their visualization by magnetic resonance imaging (MRI) remains challenging.Objectives: We aimed at assessing the sensitivity of multi echo gradient echo (ME-GRE) T2-weighted MRI at 7.0 Tesla in depicting NLs compared to myelin and iron staining.Methods: Samples from two MS patients were imaged post mortem using a whole body 7T MRI scanner with a 24-channel receive-only array. Isotropic 200 micron resolution images with varying T2weighting were reconstructed from the ME-GRE data and converted into R2maps. Immunohistochemical staining for myelin (proteolipid protein, PLP) and diaminobenzidine-enhanced Turnbull blue staining for iron were performed.Results: Prospective and retrospective sensitivities of MRI for the detection of NLs were 48% and 67% respectively. We observed MRI maps detecting only a small portion of 20 subpial NLs extending over large cortical areas on PLP stainings. No MRI signal changes suggestive of iron accumulation in NLs were observed. Conversely, R2 maps indicated iron loss in NLs, which was confirmed by histological quantification.Conclusions: High-resolution post mortem imaging using R2 and magnitude maps permits detection of focal NLs. However, disclosing extensive subpial demyelination with MRI remains challenging.

Ercan E.,Leiden University | Magro-Checa C.,Leiden University | Valabregue R.,Center for NeuroImaging Research | Valabregue R.,University Pierre and Marie Curie | And 9 more authors.
Brain | Year: 2016

Systemic lupus erythematosus is an inflammatory autoimmune disease with multi-organ involvement. Central nervous system involvement in systemic lupus erythematosus is common and results in several neurological and psychiatric symptoms that are poorly linked to standard magnetic resonance imaging outcome. Magnetic resonance imaging methods sensitive to tissue microstructural changes, such as diffusion tensor imaging and magnetization transfer imaging, show some correlation with neuropsychiatric systemic lupus erythematosus (NPSLE) symptoms. Histological examination of NPSLE brains reveals presence of cerebral oedema, loss of neurons and myelinated axons, microglial proliferation and reactive astrocytosis, microinfacrts and diffuse ischaemic changes, all of which can affect both diffusion tensor imaging and magnetization transfer imaging in a non-specific manner. Here we investigated the underlying cell-type specific microstructural alterations in the brain of patients with systemic lupus erythematosus with and without a history of central nervous system involvement. We did so combining diffusion tensor imaging with diffusion-weighted magnetic resonance spectroscopy, a powerful tool capable of characterizing cell-specific cytomorphological changes based on diffusion of intracellular metabolites. We used a 7 T magnetic resonance imaging scanner to acquire T1-weighted images, diffusion tensor imaging datasets, and single volume diffusion-weighted magnetic resonance spectroscopy data from the anterior body of the corpus callosum of 13 patients with systemic lupus erythematosus with past NPSLE, 16 patients with systemic lupus erythematosus without past NPSLE, and 19 healthy control subjects. Group comparisons were made between patients with systemic lupus erythematosus with/without past NPSLE and healthy controls on diffusion tensor imaging metrics and on diffusion coefficients of three brain metabolites: the exclusively neuronal/axonal N-acetylaspartate, and the predominantly glial creatine + phosphocreatine and choline compounds. In patients with systemic lupus erythematosus with past NPSLE, significantly higher diffusion tensor imaging mean and radial diffusivities were accompanied by a significantly higher intracellular diffusion of total creatine (0.202 ± 0.032 μm2/ms, P = 0.018) and total choline (0.142 ± 0.031 μm2/ms, P = 0.044) compared to healthy controls (0.171 ± 0.024 μm2/ms, 0.124 ± 0.018 μm2/ms, respectively). Total N-acetylaspartate, total creatine and total choline diffusion values from all patients with systemic lupus erythematosus correlated positively with systemic lupus erythematosus disease activity index score (P = 0.033, P = 0.040, P = 0.008, respectively). Our results indicate that intracellular alterations, and in particular changes in glia, as evidenced by increase in the average diffusivities of total choline and total creatine, correlate with systemic lupus erythematosus activity. The higher diffusivity of total creatine and total choline in patients with NPSLE, as well as the positive correlation of these diffusivities with the systemic lupus erythematosus disease activity index are in line with cytomorphological changes in reactive glia, suggesting that the diffusivities of choline compounds and of total creatine are potentially unique markers for glial reactivity in response to inflammation. © 2016 The Author.

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