Ten simple rules for reporting voxel-based morphometry studies

Voxel-based morphometry [Ashburner, J. and Friston, K.J., 2000. Voxel-based morphometry—the methods. NeuroImage 11(6 Pt 1), 805–821] is a commonly used tool for studying patterns of brain change in development or disease and neuroanatomical correlates of subject characteristics. In performing a VBM study, many methodological options are available; if the study is to be easily interpretable and repeatable, the processing steps and decisions must be clearly described. Similarly, unusual methods and parameter choices should be justified in order to aid readers in judging the importance of such options or in comparing the work with other studies. This editorial suggests core principles that should be followed and information that should be included when reporting a VBM study in order to make it transparent, replicable and useful

Neuroimaging Evidence of Major Morpho-Anatomical and Functional Abnormalities in the BTBR T+TF/J Mouse Model of Autism

BTBR T+tf/J (BTBR) mice display prominent behavioural deficits analogous to the defining symptoms of autism, a feature that has prompted a widespread use of the model in preclinical autism research. Because neuro-behavioural traits are described with respect to reference populations, multiple investigators have examined and described the behaviour of BTBR mice against that exhibited by C57BL/6J (B6), a mouse line characterised by high sociability and low self-grooming. In an attempt to probe the translational relevance of this comparison for autism research, we used Magnetic Resonance Imaging (MRI) to map in both strain multiple morpho-anatomical and functional neuroimaging readouts that have been extensively used in patient populations. Diffusion tensor tractography confirmed previous reports of callosal agenesis and lack of hippocampal commissure in BTBR mice, and revealed a concomitant rostro-caudal reorganisation of major cortical white matter bundles. Intact inter-hemispheric tracts were found in the anterior commissure, ventro-medial thalamus, and in a strain-specific white matter formation located above the third ventricle. BTBR also exhibited decreased fronto-cortical, occipital and thalamic gray matter volume and widespread reductions in cortical thickness with respect to control B6 mice. Foci of increased gray matter volume and thickness were observed in the medial prefrontal and insular cortex. Mapping of resting-state brain activity using cerebral blood volume weighted fMRI revealed reduced cortico-thalamic function together with foci of increased activity in the hypothalamus and dorsal hippocampus of BTBR mice. Collectively, our results show pronounced functional and structural abnormalities in the brain of BTBR mice with respect to control B6 mice. The large and widespread white and gray matter abnormalities observed do not appear to be representative of the neuroanatomical alterations typically observed in autistic patients. The presence of reduced fronto-cortical metabolism is of potential translational relevance, as this feature recapitulates previously-reported clinical observations

Personality, Alzheimer's disease and behavioural and cognitive symptoms of dementia: the PACO prospective cohort study protocol

International audienceBACKGROUND: Alzheimer's disease is characterised by a loss of cognitive function and behavioural problems as set out in the term "Behavioural and Psychological Symptoms of Dementia". These behavioural symptoms have heavy consequences for the patients and their families. A greater understanding of behavioural symptoms risk factors would allow better detection of those patients, a better understanding of crisis situations and better management of these patients. Some retrospective studies or simple observations suggested that personality could play a role in the occurrence of behavioural symptoms. Finally, performance in social cognition like facial recognition and perspective taking could be linked to certain personality traits and the subsequent risks of behavioural symptoms. We propose to clarify this through a prospective, multicentre, multidisciplinary study. Main Objective: -To assess the effect of personality and life events on the risk of developing behavioural symptoms. Secondary Objectives: -To evaluate, at the time of inclusion, the connection between personality and performance in social cognition tests; -To evaluate the correlation between performance in social cognition at inclusion and the risks of occurrence of behavioural symptoms; -To evaluate the correlation between regional cerebral atrophy, using brain Magnetic Resonance Imaging at baseline, and the risk of behavioural symptoms.METHODS/DESIGN: Study type and Population: Prospective multicentre cohort study with 252 patients with Alzheimer's disease at prodromal or mild dementia stage. The inclusion period will be of 18 months and the patients will be followed during 18 months. The initial evaluation will include: a clinical and neuropsychological examination, collection of behavioural symptoms data (Neuropsychiatric-Inventory scale) and their risk factors, a personality study using both a dimensional (personality traits) and categorical approach, an inventory of life events, social cognition tests and an Magnetic Resonance Imaging. Patients will be followed every 6 months (clinical examination and collection of behavioural symptoms data and risk factors) during 18 months.DISCUSSION: This study aims at better identifying the patients with Alzheimer's disease at high risk of developing behavioural symptoms, to anticipate, detect and quickly treat these disorders and so, prevent serious consequences for the patient and his caregivers.TRIAL REGISTRATION: ClincalTrials.gov: NCT01297140

Neuroimaging signatures of frontotemporal dementia genetics: C9ORF72, tau, progranulin and sporadics

A major recent discovery was the identification of an expansion of a non-coding GGGGCC hexanucleotide repeat in the C9ORF72 gene in patients with frontotemporal dementia and amyotrophic lateral sclerosis. Mutations in two other genes are known to account for familial frontotemporal dementia: microtubule-associated protein tau and progranulin. Although imaging features have been previously reported in subjects with mutations in tau and progranulin, no imaging features have been published in C9ORF72. Furthermore, it remains unknown whether there are differences in atrophy patterns across these mutations, and whether regional differences could help differentiate C9ORF72 from the other two mutations at the single-subject level. We aimed to determine the regional pattern of brain atrophy associated with the C9ORF72 gene mutation, and to determine which regions best differentiate C9ORF72 from subjects with mutations in tau and progranulin, and from sporadic frontotemporal dementia. A total of 76 subjects, including 56 with a clinical diagnosis of behavioural variant frontotemporal dementia and a mutation in one of these genes (19 with C9ORF72 mutations, 25 with tau mutations and 12 with progranulin mutations) and 20 sporadic subjects with behavioural variant frontotemporal dementia (including 50% with amyotrophic lateral sclerosis), with magnetic resonance imaging were included in this study. Voxel-based morphometry was used to assess and compare patterns of grey matter atrophy. Atlas-based parcellation was performed utilizing the automated anatomical labelling atlas and Statistical Parametric Mapping software to compute volumes of 37 regions of interest. Hemispheric asymmetry was calculated. Penalized multinomial logistic regression was utilized to create a prediction model to discriminate among groups using regional volumes and asymmetry score. Principal component analysis assessed for variance within groups. C9ORF72 was associated with symmetric atrophy predominantly involving dorsolateral, medial and orbitofrontal lobes, with additional loss in anterior temporal lobes, parietal lobes, occipital lobes and cerebellum. In contrast, striking anteromedial temporal atrophy was associated with tau mutations and temporoparietal atrophy was associated with progranulin mutations. The sporadic group was associated with frontal and anterior temporal atrophy. A conservative penalized multinomial logistic regression model identified 14 variables that could accurately classify subjects, including frontal, temporal, parietal, occipital and cerebellum volume. The principal component analysis revealed similar degrees of heterogeneity within all disease groups. Patterns of atrophy therefore differed across subjects with C9ORF72, tau and progranulin mutations and sporadic frontotemporal dementia. Our analysis suggested that imaging has the potential to be useful to help differentiate C9ORF72 from these other groups at the single-subject level

Brain Morphological Signatures for Chronic Pain

Chronic pain can be understood not only as an altered functional state, but also as a consequence of neuronal plasticity. Here we use in vivo structural MRI to compare global, local, and architectural changes in gray matter properties in patients suffering from chronic back pain (CBP), complex regional pain syndrome (CRPS) and knee osteoarthritis (OA), relative to healthy controls. We find that different chronic pain types exhibit unique anatomical ‘brain signatures’. Only the CBP group showed altered whole-brain gray matter volume, while regional gray matter density was distinct for each group. Voxel-wise comparison of gray matter density showed that the impact on the extent of chronicity of pain was localized to a common set of regions across all conditions. When gray matter density was examined for large regions approximating Brodmann areas, it exhibited unique large-scale distributed networks for each group. We derived a barcode, summarized by a single index of within-subject co-variation of gray matter density, which enabled classification of individual brains to their conditions with high accuracy. This index also enabled calculating time constants and asymptotic amplitudes for an exponential increase in brain re-organization with pain chronicity, and showed that brain reorganization with pain chronicity was 6 times slower and twice as large in CBP in comparison to CRPS. The results show an exuberance of brain anatomical reorganization peculiar to each condition and as such reflecting the unique maladaptive physiology of different types of chronic pain

Untersuchungen zur Reversibilität von Volumenabnahmen der grauen Hirnsubstanz bei Patienten mit sinunasaler Riechstörung nach Nasennebenhöhlen-Operation

Bisher konnten im Bereich zentraler olfaktorischer Areale Volumenminderungen bei Beeinträchtigung des Riechvermögens nachgewiesen werden. In der vorliegenden Studie wurden MRT-Datensätze von 15 Probanden mit sinunasaler Riechstörung mittels voxelbasierter Morphometrie untersucht, bei welchen sich das Riechvermögen ca. drei Monate nach einer Nasennebenhöhlen-Operation verbessert hat (Verbesserung im SDI-Riechtest > 3 Punkte). Hierbei zeigten sich Volumenzunahmen im Bereich des anterioren Cingulums auf der rechten Seite und des Inselcortex beidseits. In der Zusammenschau der Ergebnisse konnte die angenommene Hypothese der Reversibilität von Atrophien im Bereich zentraler Riechstrukturen bei sinunasalen Dysosmien bestätigt werden

Aplicaciones de la imagen médica en psiquiatría : un estudio transversal y longitudinal en primeros episodios psicóticos

RESUMEN: La esquizofrenia es una enfermedad cerebral asociada a anomalías morfométricas cerebrales. El objetivo principal de este trabajo fue investigar la existencia de anomalías morfométricas estructurales en pacientes con un primer episodio de trastornos del espectro de la esquizofrenia y la posible progresión de dichas anomalías durante un periodo de tres años. Se incluyeron 142 pacientes del programa PAFIP con un primer episodio de trastornos del espectro de la esquizofrenia con una RM basal y un grupo de 83 sujetos sanos. Los sujetos fueron sometidos a evaluaciones clínicas cognitivas y de RM en periodos regulares durante tres años. Los resultados muestran un mayor volumen de los ventrículos laterales y del LCR cortical y un menor volumen del tálamo y del tejido cerebral total así como un menor grosor cortical en pacientes con respecto a los controles. Las alteraciones morfométricas cerebrales observadas tras un primer episodio psicótico no sufrieron un deterioro progresivo durante los tres primeros años de la enfermedad.ABSTRACT: Schizophrenia is a chronic brain disorder associated with structural brain abnormalities. The aim of this study was to investigate brain abnormalities and their likely progressive changes in patients with a schizophrenia spectrum disorder during the first 3 years after initiating antipsychotic treatment. The study included 142 patients with a schizophrenia spectrum disorder and a control group of 83 healthy subjects. Subjects received detailed clinical and cognitive assessment and structural magnetic resonance imaging (MRI) at regular time points during a 3-year follow-up period. Overall, patients showed a enlarged lateral ventricle and cortical CSF volume and a lower total brain tissue and thalamic volume, as well as a reduced cortical thickness at baseline. We did not found a progressive deterioration of those abnormalities during the three year follow-up period.La realización de este trabajo no habría sido posible sin la financiación proporcionada por el CIBERSAM, el Instituto de Salud Carlos III (PI020499, PI050427, PI060507), la SENY Fundació Research Grant 2005-0308007 y la Fundación Marqués de Valdecilla (API07/011)

Strukturelle Veränderungen des Gehirns bei chronischer Migräne

Einleitung: Magnet Resonanz Tomographie basierte Methoden wie Voxel-basierte Morphometrie (VBM) und Diffusion Tensor Imaging (DTI), erlauben einen Vergleich der grauen Substanz beziehungsweise der Mikrostruktur der weißen Substanz des Gehirns zwischen verschiedenen Gruppen. Mit Hilfe dieser Methoden konnten strukturelle Veränderungen der grauen und weißen Substanz bei Patienten mit episodischer Migräne gezeigt werden. Einige dieser Veränderungen korrelierten mit der Krankheitsdauer und der Kopfschmerzfrequenz. Diese Erkenntnisse deuten daraufhin, dass es sich bei der Migräne um eine fortschreitende Erkrankung handeln könnte. Die vorliegende Arbeit untersucht strukturelle Veränderungen des Gehirns bei chronischer und episodischer Migräne um das Konzept der Migräne als progrediente Erkrankung zu erforschen. Methodik: Konventionelle Magnetresonanz- und DTI-Sequenzen wurden von nach Alter und Geschlecht angeglichenen chronischen Migränepatienten (CM), episodischen Migränepatienten (EM), beide ohne Aura, und gesunden Kontrollprobanden (n=21 pro Gruppe) erhoben. Die Analyse der DTI- und VBM-Daten wurde anhand der Tract-based spatial statistics Methode, beziehungsweise mit Hilfe von SPM8, durchgeführt. Die Fraktionelle Anisotropie (FA), die durchschnittliche, radiale und axiale Diffusivität sowie das Volumen der grauen Substanz (GMV) wurden zwischen den drei Gruppen verglichen. Zusätzlich wurde eine Korrelationsanalyse der bildgebenden Daten mit der Krankheitsschwere und -dauer durchgeführt. Ergebnisse: Die DTI Analyse ergab bei CM im Vergleich zu Kontrollprobanden und EM keine signifikante Veränderungen. Im Gegensatz zu vorherigen Studien konnten auch bei EM verglichen mit den Kontrollprobanden keine signifikante Veränderung der weißen Substanz beobachtet werden. Die FA korrelierte nicht mit der Krankheitsdauer oder der Kopfschmerzfrequenz. In der VBM Analyse wurden im Vergleich von CM zu Kontrollprobanden signifikante GMV Zunahmen in der Amygdala, im Putamen, im Hippocampus und in der Insula beobachtet. Bei EM im Vergleich zu Kontrollprobanden waren keine signifikanten Ergebnisse zu sehen. Die Kopfschmerzfrequenz von allen Probanden mit Migräne korrelierte positive mit dem GMV im Putamen, und im frontal und temporalen Gyrus, sowie negativ mit dem GMV im Cuneus. Schlussfolgerung: Es konnten keine Veränderung der weißen Substanz bei CM beobachtet werden. Chronische Migräne scheint kein Risikofaktor für mikrostrukturelle Veränderungen der weißen Substanz in der DTI zu sein. Strukturelle Veränderungen der grauen Substanz konnten in der VBM bei CM in Regionen, die in der Schmerzbearbeitung involviert sind, nachgewiesen werden. Einige GMV Veränderungen korrelierten mit der Kopfschmerzfrequenz. Diese Ergebnisse sprechen für den Einfluss von chronischen Schmerzen auf die Hirnplastizität. Die Zunahme der grauen Substanz könnte einen Korrelat für die Anpassung des Gehirns auf wiederholte Kopfschmerzattacken sein, die zu einer Sensitisierung des zentralen Nervensystems und einem kontinuierlichen iktal-ähnlichen Zustand des Gehirns bei Patienten mit chronischer Migräne führen.Background: Magnetic resonance imaging based methods such as voxel based morphometry (VBM) and diffusion tensor imaging (DTI) enable a comparison of the gray matter as well as of the white matter of the brain, allowing a variety of previous studies to demonstrate not only gray matter alterations but also microstructural changes in the white matter, both correlating partially with the disease duration and the headache frequency, in patients with episodic migraine. These findings suggest that Migraine is a progressive disorder with evolving structural changes in the brain. The following study aims to compare the structure of the brain of patients with chronic and episodic migraine to subsequently evaluate the concept of migraine as a progressive disorder of the brain. Methods: Individually age and sex-matched subjects with chronic migraine (CM), episodic migraine (EM), both without aura, and healthy controls (n=21 per group) were submitted to conventional MRI and DTI Imaging. The microstructural analysis of the white matter was performed using tract-based spatial statistics while the gray matter alterations were determined based on SPM8 and VBM. Fractional anisotropy (FA), mean, radial and axial diffusion as well as the gray matter volume (GMV) were compared between the three groups. Moreover a correlation analysis with the headache frequency and the disease duration was performed. Results: DTI analysis revealed no changes in the white matter in CM compared to controls und EM. No significant alterations were found in EM compared to controls. The FA did not correlate neither with the disease duration nor with the headache frequency. In the VBM Analysis, significant GMV increases in CM compared to controls were identified in amygdala, putamen, hippocampus and insula. There were no significant changes in GMV in EM compared to controls. The headache frequency correlated positively with the GMV in putamen, frontal and temporal gyrus and negatively with the GMV in cuneus. Conclusion: No white matter alterations were observed in CM. Chronic migraine does not seem to be a risk factor for microstructural changes of the white matter in DTI. Structural gray matter alterations were identified in VBM in CM in regions involved in the pain processing. These results correlated partially with the disease duration and severity. The findings indicate possible progressive alterations of the plasticity of the brain in chronic migraine caused by numerous regular attacks, and may be an indication for a sensitized nervous system and a permanent ictal-like state of the brain

Técnicas de análisis basadas en voxel aplicadas a imágenes FDG-PET como apoyo en el diagnóstico de pacientes con traumatismo craneoencefálico

En el Servicio de Daño Cerebral del Hospital Valencia al Mar de Valencia, hasta ahora, el daño funcional que tienen los pacientes que han sufrido un traumatismo craneoencefálico (TCE) se evaluaba de manera cualitativa a través de imágenes FDG-PET (Fluorodeoxyglucose Positron Emission Tomography). En este trabajo de tesis se propone utilizar técnicas de análisis basado en vóxel para poder evaluar las imágenes FDG-PET de manera cuantitativa, para ello se presenta una adaptación de la metodología morfometría basada en vóxel. El objetivo final de la evaluación cuantitativa de las imágenes es que ésta sirva de apoyo para el pronóstico sobre el grado de independencia de los pacientes. Primero se aplicaron las técnicas de análisis basado en vóxel a un único caso longitudinal, en el que se disponían de dos imágenes FDG-PET de un paciente que sufre una encefalitis herpética (primera imagen) y tiene una recaída un año después (segunda imagen). En este caso se realizó una sustracción de las imágenes volumétricas PET, que fue muy útil para poder relacionar las diferentes consecuencias de cada episodio. Esto también ayudó a confirmar la hipótesis de un fenómeno bi-fásico, en contra de la hipótesis progresiva/degenerativa. A continuación, se aplicaron las técnicas de análisis basado en vóxel a nivel de grupo para estudiar la relación entre el metabolismo talámico expresado en las imágenes FDG-PET y el estado neurológico para los diferentes grupos de pacientes que han sufrido un TCE. Esto permitió conocer que existen diferencias metabólicas entre los distintos estados neurológicos y que cuanto peor fuese el estado neurológico del paciente menor metabolismo talámico tenía. El proceso de recuperación de los pacientes que han sufrido un TCE atraviesa diferentes estados neurológicos comenzando por el estado de coma. A lo largo de este proceso el personal sanitario va realizando pruebas para ver en qué estado neurológico se encuentra el paciente y en función de éste poderLull Noguera, N. (2012). Técnicas de análisis basadas en voxel aplicadas a imágenes FDG-PET como apoyo en el diagnóstico de pacientes con traumatismo craneoencefálico [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/16184Palanci