Brain morphometry and estimation of aging brain in subjects with congenital untreated isolated GH deficiency.

PURPOSE: Individuals with isolated GH deficiency (IGHD) due to a mutation in the GHRH receptor gene have a normal life expectancy and above 50 years of age, similar total cognitive performance, with better attention and executive function than controls. Our objectives were to evaluate their brain morphometry and brain aging using MRI. METHODS: Thirteen IGHD and 14 controls matched by age, sex, and education, were enrolled. Quantitative volumetric data and cortical thickness were obtained by automatic segmentation using Freesurfer software. The volume of each brain region was normalized by the intracranial volume. The difference between the predicted brain age estimated by MRI using a trained neuronal network, and the chronological age, was obtained. p < 0.005 was considered significant and 0.005 < p < 0.05 as a suggestive evidence of difference. RESULTS: In IGHD, most absolute values of cortical thickness and regional brain volumes were similar to controls, but normalized volumes were greater in the white matter in the frontal pole and in the insula bilaterally, and in the gray matter, in the right insula and in left Caudate (p < 0.005 for all comparisons) We also noticed suggestive evidence of a larger volume in IGHD in left thalamus (p = 0.006), right thalamus (p = 0.025), right caudate (p = 0.046) and right putamen (p = 0.013). Predicted brain ages were similar between groups. CONCLUSION: IGHD is primarily associated with similar absolute brain measurements, and a set of larger normalized volumes, and does not appear to alter the process of brain aging.

Preliminary findings on long-term effects of fMRI neurofeedback training on functional networks involved in sustained attention.

INTRODUCTION: Neurofeedback based on functional magnetic resonance imaging allows for learning voluntary control over one's own brain activity, aiming to enhance cognition and clinical symptoms. We previously reported improved sustained attention temporarily by training healthy participants to up-regulate the differential activity of the sustained attention network minus the default mode network (DMN). However, the long-term brain and behavioral effects of this training have not yet been studied. In general, despite their relevance, long-term learning effects of neurofeedback training remain under-explored. METHODS: Here, we complement our previously reported results by evaluating the neurofeedback training effects on functional networks involved in sustained attention and by assessing behavioral and brain measures before, after, and 2 months after training. The behavioral measures include task as well as questionnaire scores, and the brain measures include activity and connectivity during self-regulation runs without feedback (i.e., transfer runs) and during resting-state runs from 15 healthy individuals. RESULTS: Neurally, we found that participants maintained their ability to control the differential activity during follow-up sessions. Further, exploratory analyses showed that the training increased the functional connectivity between the DMN and the occipital gyrus, which was maintained during follow-up transfer runs but not during follow-up resting-state runs. Behaviorally, we found that enhanced sustained attention right after training returned to baseline level during follow-up. CONCLUSION: The discrepancy between lasting regulation-related brain changes but transient behavioral and resting-state effects raises the question of how neural changes induced by neurofeedback training translate to potential behavioral improvements. Since neurofeedback directly targets brain measures to indirectly improve behavior in the long term, a better understanding of the brain-behavior associations during and after neurofeedback training is needed to develop its full potential as a promising scientific and clinical tool.

Evaluation of multi-channel phase reconstruction methods for quantitative susceptibility mapping on postmortem human brain.

Quantitative Susceptibility Mapping (QSM) is an established Magnetic Resonance Imaging (MRI) technique with high potential in brain iron studies associated to several neurodegenerative diseases. Unlike other MRI techniques, QSM relies on phase images to estimate tissue's relative susceptibility, therefore requiring a reliable phase data. Phase images from a multi-channel acquisition should be reconstructed in a proper way. On this work it was compared the performance of combination of phase matching algorithms (MCPC3D-S and VRC) and phase combination methods based on a complex weighted sum of phases, considering the magnitude at different powers (k = 0 to 4) as the weighting factor. These reconstruction methods were applied in two datasets: a simulated brain dataset for a 4-coil array and data of 22 postmortem subjects acquired at a 7T scanner using a 32 channels coil. For the simulated dataset, differences between the ground truth and the Root Mean Squared Error (RMSE) were evaluated. For both simulated and postmortem data, the mean (MS) and standard deviation (SD) of susceptibility values of five deep gray matter regions were calculated. For the postmortem subjects, MS and SD were statistically compared across all subjects. A qualitative analysis indicated no differences between methods, except for the Adaptive approach on postmortem data, which showed intense artifacts. In the 20% noise level case, the simulated data showed increased noise in central regions. Quantitative analysis showed that both MS and SD were not statistically different when comparing k = 1 and k = 2 on postmortem brain images, however visual inspection showed some boundaries artifacts on k = 2. Furthermore, the RMSE decreased (on regions near the coils) and increased (on central regions and on overall QSM) with increasing k. In conclusion, for reconstruction of phase images from multiple coils with no reference available, alternative methods are needed. In this study it was found that overall, the phase combination with k = 1 is preferred over other powers of k.

Six-point DIXON and Magnetic Resonance Spectroscopy Techniques in Quantifying Bone Marrow Fat in Sickle Cell Disease.

RATIONALE AND OBJECTIVES: To compare bone marrow fat quantification using magnetic resonance spectroscopy (MRS) and six-point DIXON (6PD) techniques in patients with sickle cell disease (SCD) and healthy subjects. MATERIALS AND METHODS: Prospective study, with 43 SCD patients (24 homozygous [SS], 19 double heterozygous [SC), and 41 healthy subjects paired by age, weight and sex with SCD patients. All participants underwent magnetic resonance imaging with 6PD and single voxel MRS in the L3 vertebral body. Pearson's correlation, ROC curve, and bland-altman analysis were performed, p-values ​​≤0.05 were considered statistically significant for all tests. RESULTS: Significant linear correlation was found between fat fraction (FF) by 6PD and Total Lipids (TL) (r = 0.932; p < 0.001) and Saturated Lipids (SL) (r = 0.934; p < 0.001), in all subjects. Strong correlations were also identified considering subjects of the SS/SC subgroups. Despite high correlations, no significant difference was observed only between FF and SL in the SS subgroup (Bland-Altman analysis), indicating excellent agreement between the fat estimations in this specific situation. Significant differences were observed in all variables (FF, TL, SL) comparing the SCD and healthy subjects. The ROC curve between SCD and healthy subjects showed the following areas under the curve: FF(0.924) > TL(0.883) > SL(0.892). CONCLUSIONS: The comparison between fat quantification by the 6PD with MRS demonstrated an excellent correlation in SCD patients, especially in the SS subgroup, which usually has a higher degree of hemolysis. The diagnostic performance of 6PD and MRS is similar, with advantages of shorter imaging processing time and larger studied area with the 6PD.

Linking Brain Biology to Intellectual Endowment: A Review on the Associations of Human Intelligence With Neuroimaging Data.

Human intelligence has always been a fascinating subject for scientists. Since the inception of Spearman's general intelligence in the early 1900s, there has been significant progress towards characterizing different aspects of intelligence and its relationship with structural and functional features of the brain. In recent years, the invention of sophisticated brain imaging devices using Diffusion-Weighted Imaging (DWI) and functional Magnetic Resonance Imaging (fMRI) has allowed researchers to test hypotheses about neural correlates of intelligence in humans.This review summarizes recent findings on the associations of human intelligence with neuroimaging data. To this end, first, we review the literature that has related brain morphometry to intelligence. Next, we elaborate on the applications of DWI and restingstate fMRI on the investigation of intelligence. Then, we provide a survey of literature that has used multimodal DWI-fMRI to shed light on intelligence. Finally, we discuss the state-of-the-art of individualized prediction of intelligence from neuroimaging data and point out future strategies. Future studies hold promising outcomes for machine learning-based predictive frameworks using neuroimaging features to estimate human intelligence.

Qualitative and quantitative magnetic resonance imaging evaluation of bone tissue vaso-occlusive events in patients with sickle cell disease.

OBJECTIVE: To evaluate the association between bone changes due to vaso-occlusive events in sickle cell disease (SCD) revealed by conventional MRI sequences and the fat fraction obtained using a 6-point DIXON technique (FFdix), in an attempt to use quantitative data as a biomarker for bone complications. METHODS: Cross-sectional study, with 48 SCD patients, 26-homozygous (HbSS), and 22-compound heterozygous (HbSC). Forty-eight healthy individuals paired by age, weight, and sex with SCD patients. All participants underwent lumbar spine and pelvis MRI. Conventional sequences: bone complications related to vaso-occlusive events-femoral head avascular necrosis, bone infarctions, "H"-shaped vertebrae, bone marrow necrosis. Six-point DIXON technique: quantitative evaluation of the bone marrow at pre-established sites (lumbar vertebrae, sacrum, iliacs, femoral heads, greater femoral trochanters, femoral necks). Pearson's correlation, ROC curve, and binary logistic regression analysis were performed. RESULTS: The most frequent findings in the SCD group included femoral head avascular necrosis (75%), bone infarctions (58.3%), "H"-shaped vertebrae (58.3%), and typical imaging findings of bone marrow necrosis (8.3%). Cortical bone thickness in the proximal femoral diaphysis in patients with SCD was moderately negatively correlated with FFdix in lumbar vertebrae, iliacs, femoral necks, and first sacral vertebrae. The ROC curves and odds ratios demonstrated excellent performance of FFdix in all the evaluated anatomical sites and identified patients having bone complications. CONCLUSIONS: FFdix could serve as a potential biomarker in SCD because of its association with bone complications secondary to vaso-occlusive events in patients with SCD, especially in femoral heads, femoral necks, and iliacs.

Applications of the Dixon technique in the evaluation of the musculoskeletal system.

The acquisition of images with suppression of the fat signal is very useful in clinical practice and can be achieved in a variety of sequences. The Dixon technique, unlike other fat suppression techniques, allows the signal of fat to be suppressed in the postprocessing rather than during acquisition, as well as allowing the visualization of maps showing the distribution of water and fat. This review of the Dixon technique aims to illustrate the basic physical principles, to compare the technique with other magnetic resonance imaging sequences for fat suppression or fat quantification, and to describe its applications in the study of diseases of the musculoskeletal system. Many variants of the Dixon technique have been developed, providing more consistent separation of the fat and water signals, as well as allowing correction for many confounding factors. It allows homogeneous fat suppression, being able to be acquired in combination with several other sequences, as well as with different weightings. The technique also makes it possible to obtain images with and without fat suppression from a single acquisition. In addition, the Dixon technique can be used as a quantitative method, allowing the proportion of tissue fat to be determined, and, in more updated versions, can quantify tissue iron.

A aquisição de imagens com supressão do sinal da gordura é um recurso de grande utilidade diagnóstica, existindo várias sequências capazes de realizá-la. A técnica Dixon, ao contrário de outras técnicas de supressão de gordura, permite suprimir a contribuição do sinal de gordura no pós-processamento e não durante a aquisição, além de permitir a visualização de mapas com a distribuição da água e da gordura. Esta revisão sobre a técnica Dixon almeja ilustrar os princípios físicos básicos, comparar a técnica com outras sequências de ressonância magnética para supressão ou quantificação de gordura, e descrever suas aplicações no estudo de doenças do sistema musculoesquelético. Muitas variantes da técnica Dixon foram desenvolvidas, proporcionando separação mais consistente dos sinais de gordura e água e permitindo correção de muitos fatores de confusão. Permite obter supressão homogênea de gordura, podendo ser adquirida de forma combinada com várias outras sequências, bem como com diferentes ponderações. Esta técnica possibilita também a obtenção de imagens com e sem supressão de gordura a partir de uma única aquisição. Adicionalmente, a técnica Dixon pode ser utilizada como recurso quantitativo, pois permite a mensuração do porcentual de gordura e, em versões mais atualizadas, consegue quantificar ferro tecidual.

Age-related assessment of diffusion parameters in specific brain tracts correlated with cortical thinning.

The aging process is associated with many brain structural alterations. These changes are not associated with neuronal loss but can be due to cortical structural changes that may be related to white matter (WM) structural alterations. In this study, we evaluated age-related changes in WM and gray matter (GM) parameters and how they correlate for specific brain tracts in a cohort of 158 healthy individuals, aged between 18 and 83 years old. In the tract-cortical analysis, cortical regions connected by tracts demonstrated similar thinning patterns for the majority of tracts. Additionally, a significant relationship was found between mean cortical thinning rate with fractional anisotropy (FA) and mean diffusivity (MD) alteration rates. For all tracts, age was the main effect controlling diffusion parameter alterations. We found no direct correlations between cortical thickness and FA or MD, except for in the fornix, for which the subcallosal gyrus thickness was significantly correlated to FA and MD (p < 0.05 FDR corrected). Our findings lead to the conclusion that alterations in the WM diffusion parameters are explained by the aging process, also associated with cortical thickness changes. Also, the alteration rates of the structural parameters are correlated to the different brain tracts in the aging process.

Association of bone mineral density with bone texture attributes extracted using routine magnetic resonance imaging.

OBJECTIVE: Dual-energy X-ray absorptiometry (DXA)-derived bone mineral density (BMD) often fails to predict fragility fractures. Quantitative textural analysis using magnetic resonance imaging (MRI) may potentially yield useful radiomic features to predict fractures. We aimed to investigate the correlation between BMD and texture attributes (TAs) extracted from MRI scans and the interobserver reproducibility of the analysis. METHODS: Forty-nine volunteers underwent lumbar spine 1.5-T MRI and DXA. Three-dimensional (3-D) gray-level co-occurrence matrices were measured from routine sagittal T2 fast spin-echo images using the IBEX software. Twenty-two TAs were extracted from 3-D segmented L3 vertebrae. The estimated concordance coefficient was calculated using linear regression analysis. A Pearson correlation coefficient analysis was performed to evaluate the correlation between BMD and the TAs. Interobserver reproducibility was assessed with the concordance coefficient described by Lin. RESULTS: The results revealed a fair-to-moderate significant correlation between BMD and 13 TAs (r=-0.20 to 0.39; p<0.05). Eight TAs (autocorrelation, energy, homogeneity 1, homogeneity 1.1, maximum probability, sum average, sum variance, and inverse difference normalized) negatively correlated with BMD (r=-0.20 to -0.38; p<0.05), whereas five TAs (dissimilarity, difference entropy, entropy, sum entropy, and information measure corr 1) positively correlated with BMD (r=0.29-0.39; p<0.05). The interobserver agreement was almost perfect for all significant TAs (95% confidence interval, 0.92-1.00; p<0.05). CONCLUSION: Specific TAs could be reliably extracted from routine MRI and correlated with BMD. Our results encourage future evaluation of the potential usefulness of quantitative texture measurements from MRI scans for predicting fragility fractures.

Histological correlates of hippocampal magnetization transfer images in drug-resistant temporal lobe epilepsy patients.

OBJECTIVE: Temporal lobe epilepsy patients (TLE) often present with hippocampal atrophy, increased T2 relaxation, and reduced magnetization transfer ratio (MTR) in magnetic resonance images (MRI). The histological correlates of the reduced hippocampal MTR are so far unknown. Since MTR is dependent on the tissue's macromolecules, our aim was to evaluate the correlations between cellular populations, extracellular matrix molecules and the MTR in TLE patients. METHODS: Patients with TLE (n = 26) and voluntaries (=20) were scanned in a 3 Tesla MRI scanner, and MTR images were calculated from 3DT1 sequences with magnetization pulse on resonance. Immunohistochemistry for neurons, reactive astrocytes, activated microglia, and extracellular matrix chondroitin sulfate were performed in formalin fixed, paraffin embedded tissues of TLE and autopsy controls (n = 10). Results were considered significant with adjusted p < 0.05. RESULTS: Compared to the respective controls, TLE patients had reduced hippocampal MTR, increased reactive astrocytes and activated microglia, increased extracellular chondroitin sulfate, and reduced neuron density, compares to controls. MTR correlated positively with neuron density in CA3 and with chondroitin sulfate in CA3 and CA1. Multiple linear regressions reinforced the correlations between chondroitin sulfate and MTR. SIGNIFICANCE: Our data indicate that extracellular matrix molecules are the most significant histological correlates of magnetization transfer ratio in the hippocampus of TLE patients.

Association of bone mineral density with bone texture attributes extracted using routine magnetic resonance imaging

OBJECTIVE: Dual-energy X-ray absorptiometry (DXA)-derived bone mineral density (BMD) often fails to predict fragility fractures. Quantitative textural analysis using magnetic resonance imaging (MRI) may potentially yield useful radiomic features to predict fractures. We aimed to investigate the correlation between BMD and texture attributes (TAs) extracted from MRI scans and the interobserver reproducibility of the analysis. METHODS: Forty-nine volunteers underwent lumbar spine 1.5-T MRI and DXA. Three-dimensional (3-D) gray-level co-occurrence matrices were measured from routine sagittal T2 fast spin-echo images using the IBEX software. Twenty-two TAs were extracted from 3-D segmented L3 vertebrae. The estimated concordance coefficient was calculated using linear regression analysis. A Pearson correlation coefficient analysis was performed to evaluate the correlation between BMD and the TAs. Interobserver reproducibility was assessed with the concordance coefficient described by Lin. RESULTS: The results revealed a fair-to-moderate significant correlation between BMD and 13 TAs (r=−0.20 to 0.39; p<0.05). Eight TAs (autocorrelation, energy, homogeneity 1, homogeneity 1.1, maximum probability, sum average, sum variance, and inverse difference normalized) negatively correlated with BMD (r=−0.20 to −0.38; p<0.05), whereas five TAs (dissimilarity, difference entropy, entropy, sum entropy, and information measure corr 1) positively correlated with BMD (r=0.29-0.39; p<0.05). The interobserver agreement was almost perfect for all significant TAs (95% confidence interval, 0.92-1.00; p<0.05). CONCLUSION: Specific TAs could be reliably extracted from routine MRI and correlated with BMD. Our results encourage future evaluation of the potential usefulness of quantitative texture measurements from MRI scans for predicting fragility fractures.

Anatomic and neuropsychological findings in low-educated cognitively intact elderly from a Brazilian cohort.

In elderly individuals, low educational level may represent a risk factor for the development of dementia and a proxy of cognitive reserve. OBJECTIVE: This study examined the cognitive and neuroanatomic correlates of high versus low educational levels in cognitively healthy community-dwelling older adults in Brazil. METHODS: Fifty-three older adults (mean age: 68±5.3 years) were divided into a "low education" group [LE; 1-4 years of education (N=33)] and "high education" group [HE; >11 years of education (N=20)]. Both groups completed a comprehensive neuropsychological battery and underwent in vivo structural MRI close to the time of testing. RESULTS: Higher educational level increased the chance of having better scores on neuropsychological tests, including verbal and visual delayed recall of information, verbal learning, category fluency, global cognition, and vocabulary. Better scores on these tests were observed in the HE group relative to the LE group. Despite this, there were no group differences between MRI measures. CONCLUSION: Older adults with higher educational levels showed better scores on neuropsychological measures of cognition, highlighting the need for education-adjusted norms in developing countries. Given the absence of differences in structural anatomy between the groups, these findings appear to be best explained by theories of cognitive reserve.

Sabe-se que baixos níveis de educação são comuns em países em desenvolvimento. Em indivíduos idosos, em particular, baixos níveis de educação podem representar um fator de risco para o desenvolvimento de demência. Objetivo: Este estudo examina os correlatos cognitivos e neuroanatômicos de escolaridade alta versus baixa, em idosos cognitivamente saudáveis,vivendo em comunidade no Brasil. Métodos: Cinquenta e três idosos (média de idade: 68±5,3) foram divididos em um grupo de "baixa escolaridade" [LE; 1-4 anos de escolaridade (N=33)] e um grupo de "alta escolaridade" [HE; >11 anos de escolaridade (N=20)]. Ambos os grupos completaram uma bateria neuropsicológica abrangente e foram submetidos à RM estrutural in vivo próximo à testagem. Resultados: O nível educacional aumentou a chance de se obter melhores pontuações em testes neuropsicológicos, incluindo evocação verbal e visual da informação, aprendizagem verbal, fluência de categoria, cognição global e vocabulário. Escores mais altos foram encontrados no grupo HE, em detrimento do LE. Apesar disso, não houve diferenças entre os grupos nas medidas de ressonância magnética in vivo. Conclusão: Idosos com maiores níveis de escolaridade apresentaram melhores pontuações nas medidas neuropsicológicas da cognição, destacando a necessidade de normas ajustadas à educação nos países em desenvolvimento. Não havendo diferenças na anatomia estrutural entre os grupos, os achados parecem ser melhor explicados pelas teorias da "reserva cognitiva".

Anatomic and neuropsychological findings in low-educated cognitively intact elderly from a Brazilian cohort / Achados Anatômicos e Neuropsicológicos de Idosos Cognitivamente Saudáveis com Baixa Escolaridade em uma Coorte Brasileira

ABSTRACT In elderly individuals, low educational level may represent a risk factor for the development of dementia and a proxy of cognitive reserve. Objective: This study examined the cognitive and neuroanatomic correlates of high versus low educational levels in cognitively healthy community-dwelling older adults in Brazil. Methods: Fifty-three older adults (mean age: 68±5.3 years) were divided into a "low education" group [LE; 1-4 years of education (N=33)] and "high education" group [HE; >11 years of education (N=20)]. Both groups completed a comprehensive neuropsychological battery and underwent in vivo structural MRI close to the time of testing. Results: Higher educational level increased the chance of having better scores on neuropsychological tests, including verbal and visual delayed recall of information, verbal learning, category fluency, global cognition, and vocabulary. Better scores on these tests were observed in the HE group relative to the LE group. Despite this, there were no group differences between MRI measures. Conclusion: Older adults with higher educational levels showed better scores on neuropsychological measures of cognition, highlighting the need for education-adjusted norms in developing countries. Given the absence of differences in structural anatomy between the groups, these findings appear to be best explained by theories of cognitive reserve.

RESUMO Sabe-se que baixos níveis de educação são comuns em países em desenvolvimento. Em indivíduos idosos, em particular, baixos níveis de educação podem representar um fator de risco para o desenvolvimento de demência. Objetivo: Este estudo examina os correlatos cognitivos e neuroanatômicos de escolaridade alta versus baixa, em idosos cognitivamente saudáveis,vivendo em comunidade no Brasil. Métodos: Cinquenta e três idosos (média de idade: 68±5,3) foram divididos em um grupo de "baixa escolaridade" [LE; 1-4 anos de escolaridade (N=33)] e um grupo de "alta escolaridade" [HE; >11 anos de escolaridade (N=20)]. Ambos os grupos completaram uma bateria neuropsicológica abrangente e foram submetidos à RM estrutural in vivo próximo à testagem. Resultados: O nível educacional aumentou a chance de se obter melhores pontuações em testes neuropsicológicos, incluindo evocação verbal e visual da informação, aprendizagem verbal, fluência de categoria, cognição global e vocabulário. Escores mais altos foram encontrados no grupo HE, em detrimento do LE. Apesar disso, não houve diferenças entre os grupos nas medidas de ressonância magnética in vivo. Conclusão: Idosos com maiores níveis de escolaridade apresentaram melhores pontuações nas medidas neuropsicológicas da cognição, destacando a necessidade de normas ajustadas à educação nos países em desenvolvimento. Não havendo diferenças na anatomia estrutural entre os grupos, os achados parecem ser melhor explicados pelas teorias da "reserva cognitiva".

Multimodal quantitative magnetic resonance imaging analysis with individualized postprocessing in patients with drug-resistant focal epilepsy and conventional visual inspection negative for epileptogenic lesions.

OBJECTIVES: Approximately one-third of candidates for epilepsy surgery have no visible abnormalities on conventional magnetic resonance imaging. This is extremely discouraging, as these patients have a less favorable prognosis. We aimed to evaluate the utility of quantitative magnetic resonance imaging in patients with drug-resistant neocortical focal epilepsy and negative imaging. METHODS: A prospective study including 46 patients evaluated through individualized postprocessing of five quantitative measures: cortical thickness, white and gray matter junction signal, relaxation rate, magnetization transfer ratio, and mean diffusivity. Scalp video-electroencephalography was used to suggest the epileptogenic zone. A volumetric fluid-attenuated inversion recovery sequence was performed to aid visual inspection. A critical assessment of follow-up was also conducted throughout the study. RESULTS: In the subgroup classified as having an epileptogenic zone, individualized postprocessing detected abnormalities within the region of electroclinical origin in 9.7% to 31.0% of patients. Abnormalities outside the epileptogenic zone were more frequent, up to 51.7%. In five patients initially included with negative imaging, an epileptogenic structural abnormality was identified when a new visual magnetic resonance imaging inspection was guided by information gleaned from postprocessing. In three patients, epileptogenic lesions were detected after visual evaluation with volumetric fluid-attenuated sequence guided by video electroencephalography. CONCLUSION: Although quantitative magnetic resonance imaging analyses may suggest hidden structural lesions, caution is warranted because of the apparent low specificity of these findings for the epileptogenic zone. Conversely, these methods can be used to prevent visible lesions from being ignored, even in referral centers. In parallel, we need to highlight the positive contribution of the volumetric fluid-attenuated sequence.

Multimodal quantitative magnetic resonance imaging analysis with individualized postprocessing in patients with drug-resistant focal epilepsy and conventional visual inspection negative for epileptogenic lesions

OBJECTIVES: Approximately one-third of candidates for epilepsy surgery have no visible abnormalities on conventional magnetic resonance imaging. This is extremely discouraging, as these patients have a less favorable prognosis. We aimed to evaluate the utility of quantitative magnetic resonance imaging in patients with drug-resistant neocortical focal epilepsy and negative imaging. METHODS: A prospective study including 46 patients evaluated through individualized postprocessing of five quantitative measures: cortical thickness, white and gray matter junction signal, relaxation rate, magnetization transfer ratio, and mean diffusivity. Scalp video-electroencephalography was used to suggest the epileptogenic zone. A volumetric fluid-attenuated inversion recovery sequence was performed to aid visual inspection. A critical assessment of follow-up was also conducted throughout the study. RESULTS: In the subgroup classified as having an epileptogenic zone, individualized postprocessing detected abnormalities within the region of electroclinical origin in 9.7% to 31.0% of patients. Abnormalities outside the epileptogenic zone were more frequent, up to 51.7%. In five patients initially included with negative imaging, an epileptogenic structural abnormality was identified when a new visual magnetic resonance imaging inspection was guided by information gleaned from postprocessing. In three patients, epileptogenic lesions were detected after visual evaluation with volumetric fluid-attenuated sequence guided by video electroencephalography. CONCLUSION: Although quantitative magnetic resonance imaging analyses may suggest hidden structural lesions, caution is warranted because of the apparent low specificity of these findings for the epileptogenic zone. Conversely, these methods can be used to prevent visible lesions from being ignored, even in referral centers. In parallel, we need to highlight the positive contribution of the volumetric fluid-attenuated sequence.

Manual Hippocampal Subfield Segmentation Using High-Field MRI: Impact of Different Subfields in Hippocampal Volume Loss of Temporal Lobe Epilepsy Patients.

In patients with temporal lobe epilepsy (TLE), presurgical magnetic resonance imaging (MRI) often reveals hippocampal atrophy, while neuropathological assessment indicates the different types of hippocampal sclerosis (HS). Different HS types are not discriminated in MRI so far. We aimed to define the volume of each hippocampal subfield on MRI manually and to compare automatic and manual segmentations for the discrimination of HS types. The T2-weighted images from 14 formalin-fixed age-matched control hippocampi were obtained with 4.7T MRI to evaluate the volume of each subfield at the anatomical level of the hippocampal head, body, and tail. Formalin-fixed coronal sections at the level of the body of 14 control cases, as well as tissue samples from 24 TLE patients, were imaged with a similar high-resolution sequence at 3T. Presurgical three-dimensional (3D) T1-weighted images from TLE went through a FreeSurfer 6.0 hippocampal subfield automatic assessment. The manual delineation with the 4.7T MRI was identified using Luxol Fast Blue stained 10-µm-thin microscopy slides, collected at every millimeter. An additional section at the level of the body from controls and TLE cases was submitted to NeuN immunohistochemistry for neuronal density estimation. All TLE cases were classified according to the International League Against Epilepsy's (ILAE's) HS classification. Manual volumetry in controls revealed that the dentate gyrus (DG)+CA4 region, CA1, and subiculum accounted for almost 90% of the hippocampal volume. The manual 3T volumetry showed that all TLE patients with type 1 HS (TLE-HS1) had lower volumes for DG+CA4, CA2, and CA1, whereas those TLE patients with HS type 2 (TLE-HS2) had lower volumes only in CA1 (p ≤ 0.038). Neuronal cell densities always decreased in CA4, CA3, CA2, and CA1 of TLE-HS1 but only in CA1 of TLE-HS2 (p ≤ 0.003). In addition, TLE-HS2 had a higher volume (p = 0.016) and higher neuronal density (p < 0.001) than the TLE-HS1 in DG + CA4. Automatic segmentation failed to match the manual or histological findings and was unable to differentiate TLE-HS1 from TLE-HS2. Total hippocampal volume correlated with DG+CA4 and CA1 volumes and neuronal density. For the first time, we also identified subfield-specific pathology patterns in the manual evaluation of volumetric MRI scans, showing the importance of manual segmentation to assess subfield-specific pathology patterns.

Histogram Analysis of Adrenal Lesions With a Single Measurement for 10th Percentile: Feasibility and Incremental Value for Diagnosing Adenomas.

OBJECTIVE: Our purpose was to assess whether histogram analysis of adrenal lesions from a single measurement of mean attenuation and SD, using a threshold of 10% of negative voxels, can replace voxel counting while maintaining diagnostic accuracy. MATERIALS AND METHODS: In a 4-year period, 325 adrenal lesions were detected on CT examinations of 308 consecutive patients. After exclusions, 91 patients with 108 lesions, including 20 malignant lesions and 88 adenomas (defined by histologic results or follow-up), were enrolled. Two observers retrospectively measured lesion size, mean attenuation value, and SD attenuation value and generated a pixel histogram. The 10th percentile (P10) was obtained from the conventional histogram analysis and was also calculated from the following formula: P10 = mean attenuation - (1.282 × SD). Diagnostic accuracies of the mean attenuation criterion, histogram analysis, and calculated 10th percentile were compared. RESULTS: The study group was composed of 74 patients with 88 adenomas and 17 patients with 20 malignant lesions, including seven adrenocortical carcinomas and 13 metastases; 93.1% of histograms showed normal distribution. The correlation between histogram analysis and calculated 10th percentile was 0.9827 and 0.9843 for reader 1 and 2 (p < 0.00001 for both). For both readers, sensitivity and specificity of the mean attenuation analysis were 65.9% (95% CI, 55.0-75.7%) and 100.0% (95% CI, 83.2-100%). The sensitivity and specificity of histogram analysis and calculated 10th percentile were the same, 87.5% (95% CI, 78.7-93.6%) and 95.0% (95% CI, 75.1-99.8%), for both readers. The increment increase in sensitivity was significant (p < 0.001), whereas the decrease in specificity was not (p = 0.15). CONCLUSION: For most adrenal lesions, the pixel attenuation has a gaussian distribution, allowing estimation of 10th percentile with a single measurement. The accuracy of histogram analysis and calculated 10th percentile outperformed the mean attenuation as a diagnostic criterion for nonfunctioning adenomas.

Acupuncture at ST36 exerts neuroprotective effects via inhibition of reactive astrogliosis in infantile rats with hydrocephalus.

BACKGROUND: Acupuncture has been associated with improved cerebral circulation, analgesia, neuromodulatory function and neurogenesis. In particular, acupuncture at ST36 has been widely used in several central nervous system (CNS) disorders, including neurodegenerative diseases. However, its effects on hydrocephalus have not been studied. Our aim was to evaluate the effects of acupuncture at ST36 on behaviour, motor development and reactive astrogliosis in infantile rats with hydrocephalus. METHODS: Hydrocephalus was induced in sixteen 7-day-old pup rats by injection of 20% kaolin into the cisterna magna. One day after hydrocephalus induction, acupuncture was applied once daily (for 30 min) for a total of 21 days in eight randomly selected animals (HAc group) while the remaining eight remained untreated (H group). An additional eight healthy animals were included as controls (C group). All animals were weighed daily and, from the fifth day after hydrocephalus induction, underwent MRI to determine the ventricular ratio (VR). Rats were also exposed to modified open-field tests every 3 days until the end of the experiment. After 21 days all the animals were euthanased and their brains removed for histology and immunohistochemistry. RESULTS: Hydrocephalic rats showed an increase in VR when compared with control rats (P<0.01). In addition, these animals exhibited delayed weight gain, which was attenuated with acupuncture treatment. Hydrocephalic animals treated with acupuncture performed better in open field tests (P<0.05), and had a reduction in reactive astrocyte cell density in the corpus callosum and external capsule, as assessed by GFAP (glial fibrillary acidic protein) immunohistochemistry (P<0.05). CONCLUSIONS: These findings indicate that acupuncture at ST36 has a neuroprotective potential mediated, in part, by inhibition of astrogliosis.

Correlations between changes in the hypothalamic-pituitary-adrenal axis and neurochemistry of the anterior cingulate gyrus in postpartum depression.

BACKGROUND: This study aimed to investigate associations between indicators of hypothalamic-pituitary-adrenal axis (HPA) functioning and metabolite levels in the anterior cingulate gyrus (ACG) of women with postpartum depression (PPD). METHODS: The sample (mean age = 28.5 ±â€¯4.6 years) consisted of 20 women with PPD and 19 postpartum euthymic (PPE) women. Brain metabolites were quantified by proton magnetic resonance spectroscopy (1H-MRS). Salivary cortisol samples were collected upon awakening and 30 min and 12 h later, at 20.6 ±â€¯6.6 (PPD) and 23.0 ±â€¯7.4 (PPE) weeks after childbirth. RESULTS: There were no significant differences between groups in respect to metabolite levels in the ACG. Compared with PPE, PPD women had less diurnal variation (DVr%). In the PPD group, positive correlations were found between DVr% and myo-inositol (mI/Cr) levels, and between cortisol awakening response (CARi%) and glutamate + glutamine (Glx/Cr) levels. The correlation between CARi% and Glx/Cr remained significant even after controlling for the interval, in weeks, from birth and MR spectroscopy and to hormonal data collection, and the use of contraceptives. LIMITATIONS: The limitations of the study include the small sample size and the use of oral contraceptives by around half of the sample. CONCLUSIONS: In the remote postpartum period (mean 21.8 ±â€¯6.9 weeks) and in the presence of depressive episodes, the decreased responsiveness of the HPA axis after awakening and a smaller decrease in cortisol levels over the day were associated with lower levels of metabolites in the ACG. These results may contribute to the development of biological models to explain the etiology of PPD.