Structural and functional brain changes in middle-aged type 2 diabetic patients: a cross-sectional study.

BACKGROUND Type 2 diabetes mellitus (T2DM) is an emerging risk factor for cognitive impairment. Whether this impairment is a direct effect of this metabolic disorder on brain function, a consequence of vascular disease, or both, remains unknown. Structural and functional neuroimaging studies in patients with T2DM could help to elucidate this question. OBJECTIVE We designed a cross-sectional study comparing 25 T2DM patients with 25 age- and gender-matched healthy control participants. Clinical information, APOE genotype, lipid and glucose analysis, structural cerebral magnetic resonance imaging including voxel-based morphometry, and F-18 fluorodeoxyglucose positron emission tomography were obtained in all subjects. METHODS Gray matter densities and metabolic differences between groups were analyzed using statistical parametric mapping. In addition to comparing the neuroimaging profiles of both groups, we correlated neuroimaging findings with HbA1c levels, duration of T2DM, and insulin resistance measurement (HOMA-IR) in the diabetic patients group. Results: Patients with T2DM presented reduced gray matter densities and reduced cerebral glucose metabolism in several fronto-temporal brain regions after controlling for various vascular risk factors. Furthermore, within the T2DM group, longer disease duration, and higher HbA1c levels and HOMA-IR were associated with lower gray matter density and reduced cerebral glucose metabolism in fronto-temporal regions. CONCLUSION In agreement with previous reports, our findings indicate that T2DM leads to structural and metabolic abnormalities in fronto-temporal areas. Furthermore, they suggest that these abnormalities are not entirely explained by the role of T2DM as a cardiovascular risk factor.

Noninvasive functional and structural exploration of human subcortical structures with high resolution

Projecte de recerca elaborat a partir d’una estada al Max Planck Institute for Human Cognitive and Brain Sciences, Alemanya, entre 2010 i 2012. El principal objectiu d’aquest projecte era estudiar en detall les estructures subcorticals, en concret, el rol dels ganglis basals en control cognitiu durant processament lingüístic i no-lingüístic. Per tal d’assolir una diferenciació minuciosa en els diferents nuclis dels ganglis basals s’utilitzà ressonància magnètica d’ultra-alt camp i alta resolució (7T-MRI). El còrtex prefrontal lateral i els ganglis basals treballant conjuntament per a mitjançar memòria de treball i la regulació “top-down” de la cognició. Aquest circuit regula l’equilibri entre respostes automàtiques i d’alt-ordre cognitiu. Es crearen tres condicions experimentals principals: frases/seqüències noambigües, no-gramatical i ambigües. Les frases/seqüències no-ambigües haurien de provocar una resposta automàtica, mentre les frases/seqüències ambigües i no-gramaticals produïren un conflicte amb la resposta automàtica, i per tant, requeririen una resposta de d’alt-ordre cognitiu. Dins del domini de la resposta de control, la ambigüitat i no-gramaticalitat representen dues dimensions diferents de la resolució de conflicte, mentre per una frase/seqüència temporalment ambigua existeix una interpretació correcte, aquest no és el cas per a les frases/seqüències no-gramaticals. A més, el disseny experimental incloïa una manipulació lingüística i nolingüística, la qual posà a prova la hipòtesi que els efectes són de domini-general; així com una manipulació semàntica i sintàctica que avaluà les diferències entre el processament d’ambigüitat/error “intrínseca” vs. “estructural”. Els resultats del primer experiment (sintax-lingüístic) mostraren un gradient rostroventralcaudodorsal de control cognitiu dins del nucli caudat, això és, les regions més rostrals sostenint els nivells més alts de processament cognitiu

Postmortem imaging of sudden cardiac death

Postmortem imaging is increasingly used in forensic practice in cases of natural deaths related to cardiovascular diseases, which represent the most common causes of death in developed countries. While radiological examination is generally considered to be a good complement for conventional autopsy, it was thought to have limited application in cardiovascular pathology. At present, multidetector computed tomography (MDCT), CT angiography, and cardiac magnetic resonance imaging (MRI) are used in postmortem radiological investigation of cardiovascular pathologies. This review presents the actual state of postmortem imaging for cardiovascular pathologies in cases of sudden cardiac death (SCD), taking into consideration both the advantages and limitations. The radiological evaluation of ischemic heart disease (IHD), the most frequent cause of SCD in the general population of industrialized countries, includes the examination of the coronary arteries and myocardium. Postmortem CT angiography (PMCTA) is very useful for the detection of stenoses and occlusions of coronary arteries but less so for the identification of ischemic myocardium. MRI is the method of choice for the radiological investigation of the myocardium in clinical practice, but its accessibility and application are still limited in postmortem practice. There are very few reports implicating postmortem radiology in the investigation of other causes of SCD, such as cardiomyopathies, coronary artery abnormalities, and valvular pathologies. Cardiomyopathies representing the most frequent cause of SCD in young athletes cannot be diagnosed by echocardiography, the most widely available technique in clinical practice for the functional evaluation of the heart and the detection of cardiomyopathies. PMCTA and MRI have the potential to detect advanced stages of diseases when morphological substrate is present, but these methods have yet to be sufficiently validated for postmortem cases. Genetically determined channelopathies cannot be detected radiologically. This review underlines the need to establish the role of postmortem radiology in the diagnosis of SCD.

Reproducibility of 3D free-breathing magnetic resonance coronary vessel wall imaging.

AIMS: Although the coronary artery vessel wall can be imaged non-invasively using magnetic resonance imaging (MRI), the in vivo reproducibility of wall thickness measures has not been previously investigated. Using a refined magnetization preparation scheme, we sought to assess the reproducibility of three-dimensional (3D) free-breathing black-blood coronary MRI in vivo. METHODS AND RESULTS: MRI vessel wall scans parallel to the right coronary artery (RCA) were obtained in 18 healthy individuals (age range 25-43, six women), with no known history of coronary artery disease, using a 3D dual-inversion navigator-gated black-blood spiral imaging sequence. Vessel wall scans were repeated 1 month later in eight subjects. The visible vessel wall segment and the wall thickness were quantitatively assessed using a semi-automatic tool and the intra-observer, inter-observer, and inter-scan reproducibilities were determined. The average imaged length of the RCA vessel wall was 44.5+/-7 mm. The average wall thickness was 1.6+/-0.2 mm. There was a highly significant intra-observer (r=0.97), inter-observer (r=0.94), and inter-scan (r=0.90) correlation for wall thickness (all P<0.001). There was also a significant agreement for intra-observer, inter-observer, and inter-scan measurements on Bland-Altman analysis. The intra-class correlation coefficients for intra-observer (r=0.97), inter-observer (r=0.92), and inter-scan (r=0.86) analyses were also excellent. CONCLUSION: The use of black-blood free-breathing 3D MRI in conjunction with semi-automated analysis software allows for reproducible measurements of right coronary arterial vessel-wall thickness. This technique may be well-suited for non-invasive longitudinal studies of coronary atherosclerosis.

A coherent neurobiological framework for functional neuroimaging provided by a model integrating compartmentalized energy metabolism.

Functional neuroimaging has undergone spectacular developments in recent years. Paradoxically, its neurobiological bases have remained elusive, resulting in an intense debate around the cellular mechanisms taking place upon activation that could contribute to the signals measured. Taking advantage of a modeling approach, we propose here a coherent neurobiological framework that not only explains several in vitro and in vivo observations but also provides a physiological basis to interpret imaging signals. First, based on a model of compartmentalized energy metabolism, we show that complex kinetics of NADH changes observed in vitro can be accounted for by distinct metabolic responses in two cell populations reminiscent of neurons and astrocytes. Second, extended application of the model to an in vivo situation allowed us to reproduce the evolution of intraparenchymal oxygen levels upon activation as measured experimentally without substantially altering the initial parameter values. Finally, applying the same model to functional neuroimaging in humans, we were able to determine that the early negative component of the blood oxygenation level-dependent response recorded with functional MRI, known as the initial dip, critically depends on the oxidative response of neurons, whereas the late aspects of the signal correspond to a combination of responses from cell types with two distinct metabolic profiles that could be neurons and astrocytes. In summary, our results, obtained with such a modeling approach, support the concept that both neuronal and glial metabolic responses form essential components of neuroimaging signals.

Coronary artery imaging by magnetic resonance.

Non-invasive visualization of the coronary arteries represents a major challenge in modern cardiology, but this goal may be achieved in the near future by MR angiography. Possible applications are non-invasive diagnosis of coronary artery disease, and follow-up examinations for therapy control after PTCA, in order to detect restenosis at an early stage. A multiple slice technique (2 mm slice thickness, with a spatial resolution of 1 x 1 mm, Philips Gyroscan ACS-II, 1.5 Tesla) was used. Ten volunteers were imaged and 10 patients with coronary artery disease were examined before and after PTCA. MR measurements were validated by quantitative coronary angiography. The diameters of the proximal coronary arteries as measured by both methods were compared, and a good correlation was found (r = 0.76). Thus, it is concluded that non-invasive visualization of the coronary arteries is possible before and after PTCA and allows to determine potential restenoses. However, patient cooperation is essential for good image quality. Moreover, limited spatial image resolution and breathing artifacts restrict MR coronary angiography today to be used as a routine diagnostic tool for the diagnosis of coronary artery disease.

Progression of human carotid and femoral atherosclerosis: a prospective follow-up study by magnetic resonance vessel wall imaging.

AIMS: The time course of atherosclerosis burden in distinct vascular territories remains poorly understood. We longitudinally evaluated the natural history of atherosclerotic progression in two different arterial territories using high spatial resolution magnetic resonance imaging (HR-MRI), a powerful, safe, and non-invasive tool. METHODS AND RESULTS: We prospectively studied a cohort of 30 patients (mean age 68.3, n = 9 females) with high Framingham general cardiovascular disease 10-year risk score (29.5%) and standard medical therapy with mild-to-moderate atherosclerosis intra-individually at the level of both carotid and femoral arteries. A total of 178 HR-MRI studies of carotid and femoral arteries performed at baseline and at 1- and 2-year follow-up were evaluated in consensus reading by two experienced readers for lumen area (LA), total vessel area (TVA), vessel wall area (VWA = TVA - LA), and normalized wall area index (NWI = VWA/TVA). At the carotid level, LA decreased (-3.19%/year, P = 0.018), VWA increased (+3.83%/year, P = 0.019), and TVA remained unchanged. At the femoral level, LA remained unchanged, VWA and TVA increased (+5.23%/year and +3.11%/year, both P < 0.01), and NWI increased for both carotid and femoral arteries (+2.28%/year, P = 0.01, and +1.8%/year, P = 0.033). CONCLUSION: The atherosclerotic burden increased significantly in both carotid and femoral arteries. However, carotid plaque progression was associated with negative remodelling, whereas the increase in femoral plaque burden was compensated by positive remodelling. This finding could be related to anatomic and flow differences and/or to the distinct degree of obstruction in the two arterial territories.

Real-time MR imaging of myocardial regional function using strain-encoding (SENC) with tissue through-plane motion tracking.

PURPOSE: To implement real-time myocardial strain-encoding (SENC) imaging in combination with tracking the tissue displacement in the through-plane direction. MATERIALS AND METHODS: SENC imaging was combined with the slice-following technique by implementing three-dimensional (3D) selective excitation. Certain adjustments were implemented to reduce scan time to one heartbeat. A total of 10 volunteers and five pigs were scanned on a 3T MRI scanner. Spatial modulation of magnetization (SPAMM)-tagged images were acquired on planes orthogonal to the SENC planes for comparison. Myocardial infarction (MI) was induced in two pigs and the resulting SENC images were compared to standard delayed-enhancement (DE) images. RESULTS: The strain values computed from SENC imaging with slice-following showed significant difference from those acquired without slice-following, especially during systole (P < 0.01). The strain curves computed from the SENC images with and without slice-following were similar to those computed from the orthogonal SPAMM images, with and without, respectively, tracking the tag line displacement in the strain direction. The resulting SENC images showed good agreement with the DE images in identifying MI in infarcted pigs. CONCLUSION: Correction of through-plane motion in real-time cardiac functional imaging is feasible using slice-following. The strain measurements are more accurate than conventional SENC measurements in humans and animals, as validated with conventional MRI tagging.

Functional independence within the self-memory system: new insights from two cases of developmental amnesia.

Neuropsychological and neuroimaging data suggest that the self-memory system can be fractionated into three functionally independent systems processing personal information at several levels of abstraction, including episodic memories of one's life (episodic autobiographical memory, EAM), semantic knowledge of facts about one's life (semantic autobiographical memory, SAM), and semantic knowledge of one's personality [conceptual self, (CS)]. Through the study of two developmental amnesic patients suffering of neonatal brain injuries, we explored how the different facets of the self-memory system develop when growing up with bilateral hippocampal atrophy. Neuropsychological evaluations showed that both of them suffered from dramatic episodic learning disability with no sense of recollection (Remember/Know procedure), whereas their semantic abilities differed, being completely preserved (Valentine) or not (Jocelyn). Magnetic resonance imaging, including quantitative volumetric measurements of the hippocampus and adjacent (entorhinal, perirhinal, and temporopolar) cortex, showed severe bilateral atrophy of the hippocampus in both patients, with additional atrophy of adjacent cortex in Jocelyn. Exploration of EAM and SAM according to lifetime periods covering the entire lifespan (TEMPAu task, Piolino et al., 2009) showed that both patients had marked impairments in EAM, as they lacked specificity, details and sense of recollection, whereas SAM was completely normal in Valentine, but impaired in Jocelyn. Finally, measures of patients' CS (Tennessee Self-Concept Scale, Fitts and Warren, 1996), checked by their mothers, were generally within normal range, but both patients showed a more positive self-concept than healthy controls. These two new cases support a modular account of the medial-temporal lobe with episodic memory and recollection depending on the hippocampus, and semantic memory and familiarity on adjacent cortices. Furthermore, they highlight developmental episodic and semantic functional independence within the self-memory system suggesting that SAM and CS may be acquired without episodic memories.

Multimodal MRI analysis of structural and functional networks in the human brain : application to two clinical studies : driving abilities under THC intoxication and early white matter changes in FXTAS

Les approches multimodales dans l'imagerie cérébrale non invasive sont de plus en plus considérées comme un outil indispensable pour la compréhension des différents aspects de la structure et de la fonction cérébrale. Grâce aux progrès des techniques d'acquisition des images de Resonance Magnetique et aux nouveaux outils pour le traitement des données, il est désormais possible de mesurer plusieurs paramètres sensibles aux différentes caractéristiques des tissues cérébraux. Ces progrès permettent, par exemple, d'étudier les substrats anatomiques qui sont à la base des processus cognitifs ou de discerner au niveau purement structurel les phénomènes dégénératifs et développementaux. Cette thèse met en évidence l'importance de l'utilisation d'une approche multimodale pour étudier les différents aspects de la dynamique cérébrale grâce à l'application de cette approche à deux études cliniques: l'évaluation structurelle et fonctionnelle des effets aigus du cannabis fumé chez des consommateurs réguliers et occasionnels, et l'évaluation de l'intégrité de la substance grise et blanche chez des jeunes porteurs de la prémutations du gène FMR1 à risque de développer le FXTAS (Fragile-X Tremor Ataxia Syndrome). Nous avons montré que chez les fumeurs occasionnels de cannabis, même à faible concentration du principal composant psychoactif (THC) dans le sang, la performance lors d'une tâche visuo-motrice est fortement diminuée, et qu'il y a des changements dans l'activité des trois réseaux cérébraux impliqués dans les processus cognitifs: le réseau de saillance, le réseau du contrôle exécutif, et le réseau actif par défaut (Default Mode). Les sujets ne sont pas en mesure de saisir les saillances dans l'environnement et de focaliser leur attention sur la tâche. L'augmentation de la réponse hémodynamique dans le cortex cingulaire antérieur suggère une augmentation de l'activité introspective. Une investigation des ef¬fets au niveau cérébral d'une exposition prolongée au cannabis, montre des changements persistants de la substance grise dans les régions associées à la mémoire et au traitement des émotions. Le niveau d'atrophie dans ces structures corrèle avec la consommation de cannabis au cours des trois mois précédant l'étude. Dans la deuxième étude, nous démontrons des altérations structurelles des décennies avant l'apparition du syndrome FXTAS chez des sujets jeunes, asymptomatiques, et porteurs de la prémutation du gène FMR1. Les modifications trouvées peuvent être liées à deux mécanismes différents. Les altérations dans le réseau moteur du cervelet et dans la fimbria de l'hippocampe, suggèrent un effet développemental de la prémutation. Elles incluent aussi une atrophie de la substance grise du lobule VI du cervelet et l'altération des propriétés tissulaires de la substance blanche des projections afférentes correspondantes aux pédoncules cérébelleux moyens. Les lésions diffuses de la substance blanche cérébrale peu¬vent être un marquer précoce du développement de la maladie, car elles sont liées à un phénomène dégénératif qui précède l'apparition des symptômes du FXTAS. - Multimodal brain imaging is becoming a leading tool for understanding different aspects of brain structure and function. Thanks to the advances in Magnetic Resonance imaging (MRI) acquisition schemes and data processing techniques, it is now possible to measure different parameters sensitive to different tissue characteristics. This allows for example to investigate anatomical substrates underlying cognitive processing, or to disentangle, at a pure structural level degeneration and developmental processes. This thesis highlights the importance of using a multimodal approach for investigating different aspects of brain dynamics by applying this approach to two clinical studies: functional and structural assessment of the acute effects of cannabis smoking in regular and occasional users, and grey and white matter assessment in young FMR1 premutation carriers at risk of developing FXTAS. We demonstrate that in occasional smokers cannabis smoking, even at low concentration of the main psychoactive component (THC) in the blood, strongly decrease subjects' performance on a visuo-motor tracking task, and globally alters the activity of the three brain networks involved in cognitive processing: the Salience, the Control Executive, and the Default Mode networks. Subjects are unable to capture saliences in the environment and to orient attention to the task; the increase in Hemodynamic Response in the Anterior Cingulate Cortex suggests an increase in self-oriented mental activity. A further investigation on long term exposure to cannabis, shows a persistent grey matter modification in brain regions associated with memory and affective processing. The degree of atrophy in these structures also correlates with the estimation of drug use in the three months prior the participation to the study. In the second study we demonstrate structural changes in young asymptomatic premutation carriers decades before the onset of FXTAS that might be related to two different mechanisms. Alteration of the cerebellar motor network and of the hippocampal fimbria/ fornix, may reflect a potential neurodevelopmental effect of the premutation. These include grey matter atrophy in lobule VI and modification of white matter tissue property in the corresponding afferent projections through the Middle Cerebellar Peduncles. Diffuse hemispheric white matter lesions that seem to appear closer to the onset of FXTAS and be related to a neurodegenerative phenomenon may mark the imminent onset of FXTAS.

Virtual milgram : empathic concern or personal distress? Evidence from functional MRI and dispositional measures

One motive for behaving as the agent of another"s aggression appears to be anchored in as yet unelucidated mechanisms of obedience to authority. In a recent partial replication of Milgram"s obedience paradigm within an immersive virtual environment, participants administered pain to a female virtual human and observed her suffering. Whether the participants" response to the latter was more akin to other-oriented empathic concern for her well-being or to a self-oriented aversive state of personal distress in response to her distress is unclear. Using the stimuli from that study, this event-related fMRI-based study analysed brain activity during observation of the victim in pain versus not in pain. This contrast revealed activation in pre-defi ned brain areas known to be involved in affective processing but not in those commonly associated with affect sharing (e.g., ACC and insula). We then examined whether different dimensions of dispositional empathy predict activity within the same pre-defi ned brain regions: While personal distress and fantasy (i.e., tendency to transpose oneself into fi ctional situations and characters) predicted brain activity, empathic concern and perspective taking predicted no change in neuronal response associated with pain observation. These exploratory fi ndings suggest that there is a distinct pattern of brain activity associated with observing the pain-related behaviour of the victim within the context of this social dilemma, that this observation evoked a self-oriented aversive state of personal distress, and that the objective"reality" of pain is of secondary importance for this response. These fi ndings provide a starting point for experimentally more rigorous investigation of obedience.

Indications for cardiovascular magnetic resonance in children with congenital and acquired heart disease: an expert consensus paper of the Imaging Working Group of the AEPC and the Cardiovascular Magnetic Resonance Section of the EACVI.

This article provides expert opinion on the use of cardiovascular magnetic resonance (CMR) in young patients with congenital heart disease (CHD) and in specific clinical situations. As peculiar challenges apply to imaging children, paediatric aspects are repeatedly discussed. The first section of the paper addresses settings and techniques, including the basic sequences used in paediatric CMR, safety, and sedation. In the second section, the indication, application, and clinical relevance of CMR in the most frequent CHD are discussed in detail. In the current era of multimodality imaging, the strengths of CMR are compared with other imaging modalities. At the end of each chapter, a brief summary with expert consensus key points is provided. The recommendations provided are strongly clinically oriented. The paper addresses not only imagers performing CMR, but also clinical cardiologists who want to know which information can be obtained by CMR and how to integrate it in clinical decision-making.

Differential patterns of functional and structural plasticity within and between inferior frontal gyri support training-induced improvements in inhibitory control proficiency.

Ample evidence indicates that inhibitory control (IC), a key executive component referring to the ability to suppress cognitive or motor processes, relies on a right-lateralized fronto-basal brain network. However, whether and how IC can be improved with training and the underlying neuroplastic mechanisms remains largely unresolved. We used functional and structural magnetic resonance imaging to measure the effects of 2 weeks of training with a Go/NoGo task specifically designed to improve frontal top-down IC mechanisms. The training-induced behavioral improvements were accompanied by a decrease in neural activity to inhibition trials within the right pars opercularis and triangularis, and in the left pars orbitalis of the inferior frontal gyri. Analyses of changes in brain anatomy induced by the IC training revealed increases in grey matter volume in the right pars orbitalis and modulations of white matter microstructure in the right pars triangularis. The task-specificity of the effects of training was confirmed by an absence of change in neural activity to a control working memory task. Our combined anatomical and functional findings indicate that differential patterns of functional and structural plasticity between and within inferior frontal gyri enhanced the speed of top-down inhibition processes and in turn IC proficiency. The results suggest that training-based interventions might help overcoming the anatomic and functional deficits of inferior frontal gyri manifesting in inhibition-related clinical conditions. More generally, we demonstrate how multimodal neuroimaging investigations of training-induced neuroplasticity enable revealing novel anatomo-functional dissociations within frontal executive brain networks. Hum Brain Mapp 36:2527-2543, 2015. © 2015 Wiley Periodicals, Inc.

Functional changes of human quadriceps muscle injured by eccentric exercise

The present study evaluated functional changes of quadriceps muscle after injury induced by eccentric exercise. Maximal isometric torque of quadriceps and the surface electromyography (root mean square, RMS, and median frequency, MDF) of the vastus medialis oblique (VMO) and vastus lateralis (VL) muscles were examined before, immediately after and during the first 7 days after injury. Serum creatine kinase (CK) levels and magnetic resonance imaging (MRI) were used to identify muscle injury. The subject was used as her own control and percent refers to pre-injury data. Experiments were carried out with a sedentary 23-year-old female. Injury was induced by 4 bouts of 15 maximal isokinetic eccentric contractions (angular velocity of 5º/s; range of motion from 40º to 110º of knee flexion). The isometric torque of the quadriceps (knee at 90º flexion) decreased 52% immediately after eccentric exercise and recovered on the 5th day. The highest reduction of RMS occurred on the 2nd day after injury in both VL (63%) and VMO (66%) and only VL recovered to the pre-injury level on the 7th day. Immediately after injury, the MDF decreased by 5 and 3% (VMO and VL, respectively) and recovered one day later. Serum CK levels increased by 109% on the 2nd day and were still increased by 32% on the 7th day. MRI showed large areas of injury especially in the deep region of quadriceps. In conclusion, eccentric exercise decreased the isometric torque and electromyographic signals of quadriceps muscle, which were recovered in one week, despite the muscle regeneration signals.