People suffering from congenital anosmia show normal brain architecture although they do not have functional sense of smell. Some studies in this regard point to the changes in secondary olfactory cortex, orbitofrontal cortex (OFC), in terms of gray matter volume increase. However, diffusion tensor imaging has not been explored so far. We included 13 congenital anosmia subjects together with 15 controls and looked into various diffusion parameters like FA. Increased FA in bilateral OFC confirms the earlier studies reporting increased gray matter thickness. However, it is quite difficult to interpret FA in terms of gray matter volume. Increased FA has been seen with recovery after traumatic brain injury. Such changes in OFC point to the plastic nature of the brain.

Approximately 23% of Canadians over the age of 65 are considered frail, with that number predicted to increase up to 40% for the population over the age of 85. Frailty is a geriatric syndrome defined by the natural decline in muscle mass and function caused by the natural aging process. When developing to an excessive degree, frailty may present as a disease state, which is recognized as sarcopenia. The exact definition of sarcopenia relies on the presence of low muscle mass, strength, and/or function, but quantitative cut-off values are still a topic of debate. Understanding how biomarkers measured via diagnostic imaging such as magnetic resonance imaging (MRI) and dual-energy x-ray absorptiometry (DXA) describe skeletal muscle can allow doctors to develop a profile of sarcopenia and define predictors to aide in preventative therapy. 4 male and 9 female (mean age = 78 ± 6.5 years) participants from a frailty study underwent full-body DXA and had their dominant thigh scanned using a 3.0T MRI. DXA-derived appendicular lean mass (ALM) and MRI-derived cross-sectional area (CSA), fat fraction (FF), T2 relaxation (T2), magnetization transfer ratio (MTR), fractional anisotropy (FA) and mean diffusivity (MD) from 4 muscle groups at the mid-thigh were defined as muscle biomarkers. Pearson's correlation was calculated to identify relationships between biomarkers and a Wilcoxon rank-sum test was performed to assess the agreement of low-muscle mass characterization between ALM normalized by height (ALMI), ALM normalized by BMI (ALM/BMI), and the gold standard MRI cross-sectional area. Strong positive correlations between muscle quantity biomarkers such as ALMI and CSA were recognized within the quadriceps (p=0.0095), adductors (p=0.035), and sartorius (p=0.00065) muscles while muscle quality biomarkers such as FF and T2 showed significant positive correlation within the quadriceps (p=3.58*10^-5) and the hamstring (p=0.0042) muscles. Finally, ALM/BMI displayed a much stronger agreement in muscle mass quantification with the gold-standard of MRI-CSA over the more commonly researched ALMI from DXA. The main purpose of this study was to collate a vast array of skeletal muscle biomarkers obtained using DXA and MRI on a frail population, and show that significant correlations can be recognized from a single MRI-slice located at the mid-thigh. Additionally, this study recognized the potential of ALM/BMI as the DXA-derived biomarker of choice in muscle mass assessment of frailty. / Thesis / Master of Applied Science (MASc) / A person is diagnosed with sarcopenia when they present symptoms of low muscle mass, strength, and/or function. Defining these three criteria with objective measures has been long debated by researchers and clinicians alike. By understanding how different properties, or biomarkers, of skeletal muscle relate to one another and change as a person becomes more frail, we hope to better understand sarcopenia and identify the best measures to classify someone as sarcopenic. Being able to accurately diagnose someone as sarcopenic early allows for more effective treatment of this muscle disease. In this study, non-invasive magnetic resonance imaging (MRI) and dual energy x-ray absorptiometry (DXA) were used to measure many different biomarkers of skeletal muscle at the mid-thigh. Through characterizing these measures of muscle quality and quantity between different imaging techniques this study aimed to recognize which imaging techniques, and more specifically biomarkers, can best distinguish between a person who is sarcopenic and one who is non-sarcopenic.

Thesis (MScMedSc (Biomedical Sciences. Medical Physiology))--University of Stellenbosch, 2010. / ENGLISH ABSTRACT: HIV/AIDS is a global epidemic that accounts for a large percentage of the mortality in South Africa every year. Since the implementation of anti-retroviral treatment, HIV positive individuals have been living longer, and the cognitive impairment associated with the disease is becoming increasingly apparent. During the initial systemic infection of HIV, the virus migrates through the blood-brain barrier and inflicts axonal injury by causing upregulation of cytokines and neurotoxic proteins. HIV-associated dementia is a neuropsychological classification of cognitive impairment in HIV and a variety of symptoms have been classified as a part of the dementia complex. One of these is apathy, which is thought to be a precursor for dementia in HIV patients. Three groups of individuals have been recruited and scanned using magnetic resonance imaging (MRI) to examine changes in the brain. These are an HIV non-apathetic cohort, an HIV apathetic cohort and a healthy control cohort. Diffusion tensor imaging (DTI) is an MRI technique used to quantitatively assess white matter (WM) integrity using metrics such as fractional anisotropy (FA). Voxel-based analysis, tract-based spatial statistics (TBSS) and tractography are three established DTI analysis methods that have been applied in numerous studies. However, there are certain methodological strengths and limitations associated with each technique and therefore all three of these techniques were used to compare WM differences across groups. The frontal-subcortical pathways are known to be abnormal in apathy, and this has been demonstrated in a number of imaging studies. Most of these studies have examined apathy in the context of neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s. However, to our knowledge this is the first DTI study in HIV apathetic patients. With the tractography method, the anterior thalamic radiation and the corpus callosum were reconstructed for each individual to determine whether there were any global changes in these tracts. No significant changes were found. However, a variety of regions in the WM were significantly abnormal in the HIV cohorts when comparing the data at a voxel-based level and using TBSS. This included areas such as the genu and splenium of the corpus callosum, the internal capsule and corona radiata. Changes in frontal WM for the HIV apathy group are an indication of dysfunction in the frontal-striatal circuits, and previous literature has implicated these circuits in the neuropathology of apathy in a variety of central nervous system (CNS) disorders. / AFRIKAANSE OPSOMMING: MIV/VIGS is `n wêreldwye epidemie wat verantwoordelik is vir `n hoë sterftesyfer in Suid- Afrika elke jaar. Sedert die inleiding van anti-retrovirale behandeling, het die MIV-positiewe populasie se lewensduur verleng. Tesame met langer lewensduur, het die kognitiewe verswakking wat geassosieer word met die siekte ook meer prominent na vore gekom. Gedurende die beginstadium van sistemiese infeksie in MIV is daar `n migrasie van die virus deur die bloed-breinskans. MIV kan indirek verantwoordelik wees vir aksonale beskadiging deur verhoging van neurotoksiese proteine en sitokinien te induseer. MIV-geassosieerde demensie is `n neurosielkundige klassifikasie van kognitiewe verswakking in MIV en verskeie simptome is al geïdentifiseer as deel van die demensie kompleks. Een van die simptome is apatie en daar word gespekuleer dat dit `n voorloper is vir demensie in MIV pasiënte. Drie groepe individue was gewerf vir die studie en geskandeer deur magnetiese resonansie beeldvorming (MRB) om sodoende veranderinge in die brein te ondersoek. Die groepe was onderskeidelik `n HIV nie-apatiese kohort, `n HIV apatiese kohort en `n gesonde kontrole kohort. Diffusie tensor beelding (DTB) is `n MRB tegniek wat toegepas word om witstof integriteit te meet deur gebruik te maak van maatstawwe soos fraksionele anisotropie (FA). “Voxel-based analysis”, “tract-based spatial statistics (TBSS)” en “tractography” is drie gevestigde DTB analitiese metodes wat al in talle studies toegepas was. Daar is egter sekere metodologiese voordele en beperkings verbonde aan elke tegniek en daarom is al drie tegnieke gebruik om witstof verskille tussen groepe te vergelyk. Die frontale-subkortikale roetes in die brein is bekend vir abnormaliteite in apatie en dit was ook al gedemonstreer in verskeie studies. Die meeste van die studies het apatie ondersoek in die konteks van neurodegeneratiewe siektes soos Alzheimer se siekte en Parkinson se siekte. Maar sover ons weet is hierdie die eerste DTB studie in MIV pasiënte met apatie. Met die “tractography” metode was die anterior thalamic radiation en corpus callosum herbou vir elke individu. Dit was om te bepaal of daar enige globale veranderinge is in hierdie gebiede, maar geen beduidende veranderinge is gevind nie.`n Verskeidenheid van gebiede in die witstof was beduidend abnormaal in die MIV kohorte wanneer die data vergelyk was met “TBSS” en “voxel-based analysis.” Dit het gebiede ingesluit soos die genu en splenium van die corpus callosum, die internal capsule en die corona radiata. Veranderinge in die frontale witstof vir die MIVapatie groep is `n aanduiding van disfunksie in die frontale-striatale bane. Vorige literatuur impliseer dat hierdie bane betrokke is in die neuro-patologie van apatie in verskeie sentrale senuweestelsel (SS) steurings.

The sequence-dependent curvature and flexibility of DNA is critical for many biochemically important processes. However, few experimental methods are available for directly probing these properties at the base-pair level. One promising way to predict these properties as a function of sequence is to model DNA with a set of base-pair parameters that describe the local stacking of the different possible base-pair step combinations. In this dissertation research, we develop and study a computational model for predicting the diffusion coefficients of short, relatively rigid DNA fragments from the sequence and the base-pair parameters. We focus on diffusion coefficients because various experimental methods have been developed to measure them. Moreover, these coefficients can also be computed numerically from the Stokes equations based on the three-dimensional shape of the macromolecule. By comparing the predicted diffusion coefficients with experimental measurements, we can potentially obtain refined estimates of various base-pair parameters for DNA. Our proposed model consists of three sub-models. First, we consider the geometric model of DNA, which is sequence-dependent and controlled by a set of base-pair parameters. We introduce a set of new base-pair parameters, which are convenient for computation and lead to a precise geometric interpretation. Initial estimates for these parameters are adapted from crystallographic data. With these parameters, we can translate a DNA sequence into a curved tube of uniform radius with hemispherical end caps, which approximates the effective hydrated surface of the molecule. Second, we consider the solvent model, which captures the hydrodynamic properties of DNA based on its geometric shape. We show that the Stokes equations are the leading-order, time-averaged equations in the particle body frame assuming that the Reynolds number is small. We propose an efficient boundary element method with a priori error estimates for the solution of the exterior Stokes equations. Lastly, we consider the diffusion model, which relates our computed results from the solvent model to relevant measurements from various experimental methods. We study the diffusive dynamics of rigid particles of arbitrary shape which often involves arbitrary cross- and self-coupling between translational and rotational degrees of freedom. We use scaling and perturbation analysis to characterize the dynamics at time scales relevant to different classic experimental methods and identify the corresponding diffusion coefficients. In the end, we give rigorous proofs for the convergence of our numerical scheme and show numerical evidence to support the validity of our proposed models by making comparisons with experimental data. / text

L’Imagerie par résonance magnétique (IRM) est un outil fondamental pour l’exploration in vivo du développement du cerveau chez le fœtus, le bébé et l’enfant. Elle fournit plusieurs paramètres quantitatifs qui reflètent les changements des propriétés tissulaires au cours du développement en fonction de différents processus de maturation. Cependant, l’évaluation fiable de la maturation de la substance blanche est encore une question ouverte: d'une part, aucun de ces paramètres ne peut décrire toute la complexité des changements sous-jacents; d'autre part, aucun d'eux n’est spécifique d’un processus de développement ou d’une propriété tissulaire particulière. L’implémentation d’approches multiparamétriques combinant les informations complémentaires issues des différents paramètres IRM devrait permettre d’améliorer notre compréhension du développement du cerveau. Dans ce travail de thèse, je présente deux exemples de telles approches et montre leur pertinence pour l'étude de la maturation des faisceaux de substance blanche. La première approche fournit une mesure globale de la maturation basée sur la distance de Mahalanobis calculée à partir des différents paramètres IRM (temps de relaxation T1 et T2, diffusivités longitudinale et transverse du tenseur de diffusion DTI) chez des nourrissons (âgés de 3 à 21 semaines) et des adultes. Cette approche offre une meilleure description de l’asynchronisme de maturation à travers les différents faisceaux que les approches uniparamétriques. De plus, elle permet d'estimer les délais relatifs de maturation entre faisceaux. La seconde approche vise à quantifier la myélinisation des tissus cérébraux, en calculant la fraction de molécules d’eau liées à la myéline (MWF) en chaque voxel des images. Cette approche est basée sur un modèle tissulaire avec trois composantes ayant des caractéristiques de relaxation spécifiques, lesquelles ont été pré-calibrées sur trois jeunes adultes sains. Elle permet le calcul rapide des cartes MWF chez les nourrissons et semble bien révéler la progression de la myélinisation à l’échelle cérébrale. La robustesse de cette approche a également été étudiée en simulations. Une autre question cruciale pour l'étude du développement de la substance blanche est l'identification des faisceaux dans le cerveau des enfants. Dans ce travail de thèse, je décris également la création d'un atlas préliminaire de connectivité structurelle chez des enfants âgés de 17 à 81 mois, permettant l'extraction automatique des faisceaux à partir des données de tractographie. Cette approche a démontré sa pertinence pour l'évaluation régionale de la maturation de la substance blanche normale chez l’enfant. Pour finir, j’envisage dans la dernière partie du manuscrit les applications potentielles des différentes méthodes précédemment décrites pour l’étude fine des réseaux de substance blanche dans le cadre de deux exemples spécifiques de pathologies : les épilepsies focales et la leucodystrophie métachromatique. / Magnetic Resonance Imaging (MRI) is a fundamental tool for in vivo investigation of brain development in newborns, infants and children. It provides several quantitative parameters that reflect changes in tissue properties during development depending on different undergoing maturational processes. However, reliable evaluation of the white matter maturation is still an open question: on one side, none of these parameters can describe the whole complexity of the undergoing changes; on the other side, neither of them is specific to any particular developmental process or tissue property. Developing multiparametric approaches combining complementary information from different MRI parameters is expected to improve our understanding of brain development. In this PhD work, I present two examples of such approaches and demonstrate their relevancy for investigation of maturation across different white matter bundles. The first approach provides a global measure of maturation based on the Mahalanobis distance calculated from different MRI parameters (relaxation times T1 and T2, longitudinal and transverse diffusivities from Diffusion Tensor Imaging, DTI) in infants (3-21 weeks) and adults. This approach provides a better description of the asynchronous maturation across the bundles than univariate approaches. Furthermore, it allows estimating the relative maturational delays between the bundles. The second approach aims at quantifying myelination of brain tissues by calculating Myelin Water Fraction (MWF) in each image voxel. This approach is based on a 3-component tissue model, with each model component having specific relaxation characteristics that were pre-calibrated in three healthy adult subjects. This approach allows fast computing of the MWF maps from infant data and could reveal progression of the brain myelination. The robustness of this approach was further investigated using computer simulations. Another important issue for studying white matter development in children is bundles identification. In the last part of this work I also describe creation of a preliminary atlas of white matter structural connectivity in children aged 17-81 months. This atlas allows automatic extraction of the bundles from tractography datasets. This approach demonstrated its relevance for evaluation of regional maturation of normal white matter in children. Finally, in the last part of the manuscript I describe potential future applications of the previously developed methods to investigation of the white matter in cases of two specific pathologies: focal epilepsy and metachromatic leukodystrophy.

Les lésions de la moelle épinière ont un impact significatif sur la qualité de la vie car elles peuvent induire des déficits moteurs (paralysie) et sensoriels. Ces déficits évoluent dans le temps à mesure que le système nerveux central se réorganise, en impliquant des mécanismes physiologiques et neurochimiques encore mal connus. L'ampleur de ces déficits ainsi que le processus de réhabilitation dépendent fortement des voies anatomiques qui ont été altérées dans la moelle épinière. Il est donc crucial de pouvoir attester l'intégrité de la matière blanche après une lésion spinale et évaluer quantitativement l'état fonctionnel des neurones spinaux. Un grand intérêt de l'imagerie par résonance magnétique (IRM) est qu'elle permet d'imager de façon non invasive les propriétés fonctionnelles et anatomiques du système nerveux central. Le premier objectif de ce projet de thèse a été de développer l'IRM de diffusion afin d'évaluer l'intégrité des axones de la matière blanche après une lésion médullaire. Le deuxième objectif a été d'évaluer dans quelle mesure l'IRM fonctionnelle permet de mesurer l'activité des neurones de la moelle épinière. Bien que largement appliquées au cerveau, l'IRM de diffusion et l'IRM fonctionnelle de la moelle épinière sont plus problématiques. Les difficultés associées à l'IRM de la moelle épinière relèvent de sa fine géométrie (environ 1 cm de diamètre chez l'humain), de la présence de mouvements d'origine physiologique (cardiaques et respiratoires) et de la présence d'artefacts de susceptibilité magnétique induits par les inhomogénéités de champ, notamment au niveau des disques intervertébraux et des poumons. L'objectif principal de cette thèse a donc été de développer des méthodes permettant de contourner ces difficultés. Ce développement a notamment reposé sur l'optimisation des paramètres d'acquisition d'images anatomiques, d'images pondérées en diffusion et de données fonctionnelles chez le chat et chez l'humain sur un IRM à 3 Tesla. En outre, diverses stratégies ont été étudiées afin de corriger les distorsions d'images induites par les artefacts de susceptibilité magnétique, et une étude a été menée sur la sensibilité et la spécificité de l'IRM fonctionnelle de la moelle épinière. Les résultats de ces études démontrent la faisabilité d'acquérir des images pondérées en diffusion de haute qualité, et d'évaluer l'intégrité de voies spinales spécifiques après lésion complète et partielle. De plus, l'activité des neurones spinaux a pu être détectée par IRM fonctionnelle chez des chats anesthésiés. Bien qu'encourageants, ces résultats mettent en lumière la nécessité de développer davantage ces nouvelles techniques. L'existence d'un outil de neuroimagerie fiable et robuste, capable de confirmer les paramètres cliniques, permettrait d'améliorer le diagnostic et le pronostic chez les patients atteints de lésions médullaires. Un des enjeux majeurs serait de suivre et de valider l'effet de diverses stratégies thérapeutiques. De telles outils représentent un espoir immense pour nombre de personnes souffrant de traumatismes et de maladies neurodégénératives telles que les lésions de la moelle épinière, les tumeurs spinales, la sclérose en plaques et la sclérose latérale amyotrophique. / Spinal cord injury has a significant impact on quality of life since it can lead to motor (paralysis) and sensory deficits. These deficits evolve in time as reorganisation of the central nervous system occurs, involving physiological and neurochemical mechanisms that are still not fully understood. Given that both the severity of the deficit and the successful rehabilitation process depend on the anatomical pathways that have been altered in the spinal cord, it may be of great interest to assess white matter integrity after a spinal lesion and to evaluate quantitatively the functional state of spinal neurons. The great potential of magnetic resonance imaging (MRI) lies in its ability to investigate both anatomical and functional properties of the central nervous system non invasively. To address the problem of spinal cord injury, this project aimed to evaluate the benefits of diffusion-weighted MRI to assess the integrity of white matter axons that remain after spinal cord injury. The second objective was to evaluate to what extent functional MRI can measure the activity of neurons in the spinal cord. Although widely applied to the brain, diffusion-weighted MRI and functional MRI of the spinal cord are not straightforward. Various issues arise from the small cross-section width of the cord, the presence of cardiac and respiratory motions, and from magnetic field inhomogeneities in the spinal region. The main purpose of the present thesis was therefore to develop methodologies to circumvent these issues. This development notably focused on the optimization of acquisition parameters to image anatomical, diffusion-weighted and functional data in cats and humans at 3T using standard coils and pulse sequences. Moreover, various strategies to correct for susceptibility-induced distortions were investigated and the sensitivity and specificity in spinal cord functional MRI was studied. As a result, acquisition of high spatial and angular diffusion-weighted images and evaluation of the integrity of specific spinal pathways following spinal cord injury was achieved. Moreover, functional activations in the spinal cord of anaesthetized cats was detected. Although encouraging, these results highlight the need for further technical and methodological development in the near-future. Being able to develop a reliable neuroimaging tool for confirming clinical parameters would improve diagnostic and prognosis. It would also enable to monitor the effect of various therapeutic strategies. This would certainly bring hope to a large number of people suffering from trauma and neurodegenerative diseases such as spinal cord injury, tumours, multiple sclerosis and amyotrophic lateral sclerosis.

L'objectif de cette thèse est de fournir une chaine de traitement complète pour la reconstruction des faisceaux de la matière blanche à partir d'images pondérées en diffusion caractérisées par une faible résolution angulaire. Cela implique (i) d'inférer en chaque voxel un modèle de diffusion à partir des images de diffusion et (ii) d'accomplir une ''tractographie", i.e., la reconstruction des faisceaux à partir de ces modèles locaux. Notre contribution en modélisation de la diffusion est une nouvelle distribution statistique dont les propriétés sont étudiées en détail. Nous modélisons le phénomène de diffusion par un mélange de telles distributions incluant un outil de sélection de modèle destiné à estimer le nombre de composantes du mélange. Nous montrons que le modèle peut être correctement estimé à partir d'images de diffusion ''single-shell" à faible résolution angulaire et qu'il fournit des biomarqueurs spécifiques pour l'étude des tumeurs. Notre contribution en tractographie est un algorithme qui approxime la distribution des faisceaux émanant d'un voxel donné. Pour cela, nous élaborons un filtre particulaire mieux adapté aux distributions multi-modales que les filtres traditionnels. Pour démontrer l'applicabilité de nos outils en usage clinique, nous avons participé aux trois éditions du MICCAI DTI Tractography challenge visant à reconstruire le faisceau cortico-spinal à partir d'images de diffusion ''single-shell" à faibles résolutions angulaire et spatiale. Les résultats montrent que nos outils permettent de reconstruire toute l'étendue de ce faisceau. / The objective of this thesis is to provide a complete pipeline that achieves an accurate reconstruction of the white matter fascicles using clinical diffusion images characterized by a low angular resolution. This involves (i) a diffusion model inferred in each voxel from the diffusion images and (ii) a tractography algorithm fed with these local models to perform the actual reconstruction of fascicles. Our contribution in diffusion modeling is a new statistical distribution, the properties of which are extensively studied. We model the diffusion as a mixture of such distributions, for which we design a model selection tool that estimates the number of mixture components. We show that the model can be accurately estimated from single shell low angular resolution diffusion images and that it provides specific biomarkers for studying tumors. Our contribution in tractography is an algorithm that approximates the distribution of fascicles emanating from a seed voxel. We achieve that by means of a particle filter better adapted to multi-modal distributions than the traditional filters. To demonstrate the clinical applicability of our tools, we participated to all three editions of the MICCAI DTI Tractography challenge aiming at reconstructing the cortico-spinal tract from single-shell low angular and low spatial resolution diffusion images. Results show that our pipeline provides a reconstruction of the full extent of the CST.

<p>Uvod: Dijabetes melitus (DM) je oboljenje koje poprima karakteristike globalne epidemije. Sve ţe&scaron;&scaron;e oboljevaju pacijenti mlaŤeg ţivotnog doba. Simptomi DM tip 2 su blagi, ţesto neprimetni, te se oboljenje otkriva kada se ve&scaron; manifestuju komplikacije. Dijabetesna nefropatija (DN) je jedna od mnogobrojnih komplikacija dijabetes melitusa tip 2, koja se zavr&scaron;ava terminalnom bubreţnom insuficijencijom. DN se ţesto neblagovremeno dijagnostikuje, zbog ţega se kasno zapoţinje leţenje. Rano otkrivanje DN od kljuţnog je znaţaja, jer omogu&scaron;ava primenu terapijskih postupaka usmerenih na oţuvanje preostalih zdravih nefrona i prevenciju terminalne bubreţne slabosti. Cilj: Prikazati poreme&scaron;aj difuzije molekula vode unutar bubrega kod DN, kori&scaron;&scaron;enjem mapa prividnog koeficijenta difuzije, kvantifikacijom vrednosti prividnog koeficijenta difuzije (ADC) i frakcione anizotropije (FA). Materijal i metode: U prospektivnu studiju bilo je ukljuţeno 10 zdravih dobrovoljaca i 91 pacijent oboleo od DM tip 2. Pacijenti oboleli od DM tip 2 podeljeni su u ţetiri grupe na osnovu vrednosti procenjene jaţine glomerularne filtracije (JGF) (grupe: I JGF &ge; 90, II 89-60, III 59-30, IV &le; 29 ml/min/1,73m&sup2;). Svim ispitanicima uraŤen je MR pregled bubrega, uz primenu DWI (b=0 i b=400 s/mm&sup2;) i DTI (b=1000 s/mm&sup2;) sekvence, na aparatu jaţine 1.5T. ADC i FA vrednosti raţunate su u &scaron;est regija od interasa, po tri u korteksu i meduli svakog bubrega. Dobijene vrednosti komparirane su sa laboratorijskim parametrima bubreţne funkcije (urea, kreatinin, mokra&scaron;na kiselina) i procenjenom JGF. Rezultati: Ne postoje statistiţki znaţajne razlike ADC i FA vrednosti parenhima, korteksa i medule levog i desnog bubrega kod zdravih dobrovoljaca i DM pacijenata. Kod DM pacijenata ADC je ve&scaron;a u korteksu nego u meduli (p=0,00), a FA vrednost je ve&scaron;a u meduli nego u korteksu (p=0,284). Urea, kreatinin i cistatin C imaju negativnu korelaciju sa ADC korteksa, medule i parenhima (p&lt;0,05), a JGF ima pozitivnu korelaciju sa ADC korteksa, medule i parenhima, kao i sa FA medule (p&lt;0,05) kod DM pacijenata. Na osnovu Post hoc testa za ADC, kod DM pacijenata postoje razlike izmeŤu I i IV grupe, izmeŤu II i IV grupe i III i IV grupe (p&le;0,05). IzmeŤu godina ţivota, teţine, BMI, JGF, HbA1c, uree i &Scaron;UK-a, postoji razlika DM pacijenata i zdravih dobrovoljaca (p&lt;0,05). Niţa je vrednost FA medule DM pacijenata u odnosu na zdrave dobrovoljce (p&lt;0,05). Postoji razlika ADC korteksa, medule i parenhima izmeŤu zdravih dobrovoljaca i DM pacijenata IV grupe, kao izmeŤu DM pacijenata I i II grupe u odnosu na IV grupu. TakoŤe postoji razlika izmeŤu FA medule zdravih dobrovoljaca i DM pacijenata I i IV grupe (p&lt;0,05). Regresiona analiza pokazala je uticaj kreatinina na ADC desnog bubrega i ADC oba bubrega, dok procenjena JGF i cistatin C imaju uticaj na ADC desnog i levog bubrega, ADC oba bubrega i FA levog bubrega (p&lt;0,05). Traktografija je prikazala naru&scaron;enu arhitektoniku kod pacijenata sa o&scaron;te&scaron;enom bubreţnom funkcijom. Zakljuţak: Postoji korelacija laboratorijskih parametara bubreţne funkcije i procenjene JGF sa ADC i FA vrednostima bubrega, &scaron;to ukazuje na ulogu funkcionalnog magnetno rezonantnog imidţinga u dijagnostici dijabetesne nefropatije. Neophodna su dalja istraţivanja koja &scaron;e doprineti standardizaciji MR protokola i potvrdi znaţaja MR biomarkera u dijagnostici DN. Na osnovu na&scaron;ih rezultata vrednost FA medule osetljiviji je parametar od ADC vrednosti u otkrivanju ranog o&scaron;te&scaron;enja bubrega u sklopu dijabetes melitusa.</p> / <p>Introduction: Diabetes mellitus (DM) is a disease that takes on the characteristics of a global epidemic. Patients of younger age are more and more commonly affected. Symptoms of type 2 DM are mild, often imperceptible, and therefore the disease is usually detected when complications are already manifested. Diabetic nephropathy (DN) is one of the many complications of type 2 diabetes mellitus that leads to terminal renal failure. Diagnosis of DN is often late, causing the delay of the treatmen. Early detection of DN is crucial because it allows the application of therapeutic procedures aimed at preserving the remaining healthy nephrons and preventing terminal renal failure. Objective: To investigate a diffusion of water molecule within a kidney in DN using apparent diffusion coefficient maps, by quantification of the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values in diabetic patients with DM type 2. Material and methods: The prospective study comprised 10 healthy volunteers and 91 DM type 2 patients. DM patients were divided into four groups based on the values of the estimated glomerular filtration (eGFR) (groups: I eGFR &ge; 90, II 89-60, III 59-30, IV &le; 29 ml/min/1.73m&sup2;). All subjects were scanned by 1.5T MR using DWI (b=0 and b=400 s/mm&sup2;) and DTI (b=1000 s/mm&sup2;) sequences. ADC and FA values were calculated in six regions of interest, three in cortex and three in medulla of each kidney. Obtaned values were compared to laboratory parameters of renal function (urea, creatinine, uric acid) and eGFR. Results: There were no statistically significant differences between ADC and FA values of parenchyma, cortex and medulla of the left and the right kidney in healthy volunteers and DM patients. In DM patients, the ADC value was higher in the cortex than in the medulla (p=0.00) and the FA value was higher in the medulla than in the cortex (p=0.284). The negative correlation was found between urea, creatinine and cystatin C with ADC cortex, medulla and parenchyma (p&lt;0.05), and the eGFR was positively correlated with ADC cortex, medulla and parenchyma, and with FA medulla (p&lt;0.05) in DM patients. Based on the Post hoc test for ADC, in DM patients there were differences between I and IV group, between II and IV group, III and IV group (p&le;0,05). Regarding age, weight, BMI, GFR, HbA1c, urea, and glucose in the serum, there was a difference between DM patients and healthy volunteers (p&lt;0.05). The FA of medulla in DM patients was lower than of healthy volunteers (p&lt;0.05). There were differences in ADC of cortex, medulla, and parenchyma between healthy volunteers and DM patients of IV group, as well as between DM patients of I and II group compared to IV group. There were differences of medulla FA values between healthy volunteers and group I, accompanied by healthy and IV group of DM patients (p&lt;0.05). Regression analysis showed the influence of creatinine on ADC of right kidney and ADC of both kidneys, while eGFR and cystatin C have an effect on ADC of right and left kidney, ADC of both kidneys and FA of left kidney (p&lt;0.05). The tractography showed the disturbed architectonics in patients with impaired renal function. Conclusion: There is correlation of laboratory parameters of renal function and eGFR with ADC and FA values of the kidney, indicating the role of functional magnetic resonance imaging in the diagnosis of DN. Further research that will contribute to standardizing the MR protocol and confirming the importance of MRI biomarker in the diagnosis of DN are needed. Based on our results, the values of medulla FA is more sensitive parameter than the ADC value in detecting early kidney damage in the context of diabetes mellitus.</p>

INTRODUÇÃO: O transtorno do déficit de atenção com hiperatividade (TDAH) é um transtorno do neurodesenvolvimento ainda pouco estudado na população idosa. Déficits em funções atencionais, executivas e de memória, além de anormalidades neuroanatômicas, são observados em indivíduos adultos com TDAH. Entretanto, em idosos com TDAH tais alterações ainda são pouco estudadas. OBJETIVOS: Investigar características clínicas e neuropsicológicas, alterações no volume da substância cinzenta (SC) e da substância branca (SB) cerebral, assim como alterações em microestruturas da SB em idosos com TDAH comparando com idosos sem TDAH. MÉTODOS: A amostra foi composta por 63 indivíduos, sendo 28 com TDAH (19 mulheres), diagnosticados conforme o DSM-IV e 35 controles (29 mulheres) com idade >= 65 anos. Na avaliação clínica utilizaram-se as seguintes escalas e entrevistas: Mini Mental State Examination (MMSE); Adult ADHD Self-Report Scale (ASRS-18) ; Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children/Present and Lifetime Version (K-SADS-PL); Inventário Beck de Ansiedade (BAI); Geriatric Depression Scale (GDS); Structural Clinical Interview for DSM-IV (SCID); Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) e o Memory Complaint Questionnaire (MAC-Q). Os instrumentos utilizados na testagem cognitiva visaram avaliar o QI estimado, as funções atencionais, executivas e de memória e, adicionalmente tempo de reação e variabilidade de respostas, funções visoespaciais/visoconstrutivas e visoperceptivas. As imagens de ressonância magnética (RM) foram adquiridas em aparelho de 1.5 T. Duas sequências de imagens foram obtidas. Uma pela técnica da volumetria baseada no voxel (VBM) para comparação de volumes da SC e SB e a outra, por imagem por tensor de difusão (DTI), para comparação dos valores de anisotropia fracionada (AF). RESULTADOS: O grupo TDAH apresentou maior frequência de repetência escolar e de vezes repetidas, menor frequência de aposentadoria formal, mais divórcios; mais sintomas de depressão e ansiedade, maior frequência de uso atual de antidepressivo. Houve uma correlação positiva entre sintomas de desatenção e hiperatividade/impulsividade e de depressão e ansiedade. Houve uma correlação negativa entre idade e sintomas de TDAH. Os grupos não se diferenciaram estatisticamente nos testes cognitivos e houve uma tendência de correlação entre sintomas de desatenção e os resultados dos testes de atenção. Sintomas de depressão influenciaram a memória operacional, memória episódica e função visoespacial. Mais sintomas de ansiedade refletiram uma maior variabilidade no tempo de respostas. Na neuroimagem, homens com TDAH apresentaram um volume total de SC menor que os homens do grupo controle. Os grupos não se diferenciaram quanto ao volume de SB. O grupo TDAH apresentou um cluster de volume de SC menor no giro frontal medial orbital direito e que se estende em direção ao giro frontal superior medial, giro frontal superior e o córtex do cíngulo anterior subgenual. Sintomas de desatenção se correlacionaram negativamente com o volume da SC do cíngulo anterior (bilateralmente) e positivamente com o volume do cerebelo esquerdo. Sintomas de Hiperatividade/impulsividade se correlacionaram negativamente com volume da SC em região do córtex órbito-frontal esquerdo. Sintomas de depressão se correlacionaram negativamente com o volume de SC do caudado (bilateralmente) e positivamente com o volume de SC na região parietal inferior direita. Os grupos não se diferenciaram quanto aos valores da AF. Sintomas de ansiedade se correlacionaram positivamente com AF nos tratos do corpo caloso e do fascículo longitudinal superior. CONCLUSÃO: O presente estudo evidenciou correlatos neurais em regiões relacionadas às funções atencionais, ao controle executivo e ao processamento afetivo no idoso com TDAH, sugerindo que prejuízos em regiões fronto-estriatal e fronto-parietal-cerebelar verificados em adultos com TDAH persistem na velhice. Os achados reforçam os conhecimentos sobre o TDAH em idosos, sugerindo um desempenho cognitivo objetivo comparável aos controles sem o transtorno, uma redução dos sintomas centrais com o aumento da idade, embora mantendo uma funcionalidade mais prejudicada e comorbidades / INTRODUCTION: Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that has not yet been studied in the elderly population. Deficits in attentional, executive and memory functions, in addition to neuroanatomical abnormalities, are found in younger individuals with ADHD. However, in elderly with ADHD such changes are still poorly studied. OBJECTIVES: To investigate clinical and neuropsychological characteristics, changes in cerebral gray matter (GM) and white matter (WM) volumes, as well as alterations in WM microstructures in elderly with ADHD compared with elderly without ADHD. METHODS: The sample consisted of 63 individuals, 28 ADHD (19 women) according to DSM-IV criteria and 35 controls (29 women) aged >= 65 years. In the clinical evaluation the following scales and interviews were used: Mini Mental State Examination; Adult ADHD Self-Report Scale (ASRS-18); Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children / Present and Lifetime Version (K-SADS-PL); Beck Anxiety Inventory (BAI); Geriatric Depression Scale (GDS); Structural Clinical Interview for DSM-IV (SCID); Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) and the Memory Complaint Questionnaire (MAC-Q). The neuropsychological instruments aimed to access estimated IQ, attention, executive and memory functions and, additionally, response time and response variability, visuospatial/visuoconstructive and visuoperceptive functions. Magnetic resonance imaging (MRI) was acquired in a 1.5-T equipment. Two image sequences were obtained. One by the voxel-based volumetry (VBM) technique for comparison of GM and WM volumes and the other by diffusion tensor imaging (DTI), for comparison of fractional anisotropy (FA) values. RESULTS: The ADHD group presented a higher frequency of subjects with school repetition and number of times repeated, lower frequency of formal retirement, more divorces; more depressive and anxiety symptoms, a higher frequency of current antidepressant. There was a positive correlation between inattention and hyperactivity/impulsivity symptoms and depressive and anxiety symptoms. There was a negative correlation between age and ADHD symptoms. The groups did not differ statistically in the cognitive tests and there was a tendency of correlation between symptoms of inattention and the results of the attention tests. Symptoms of depression influenced working and episodic memory and visuospatial function. More anxiety symptoms reflected on a greater variability in response time. In neuroimaging, men with ADHD had a lower total GM volume than men in the control group. The groups did not differ regarding the WM volume. The ADHD group presented a cluster of lower GM volume in the right frontal medial orbital gyrus extending towards to frontal superior medial, frontal superior and the subgenual anterior cingulate cortex. Inattention symptoms negatively correlated with GM volume in both the right and left anterior cingulate cortex and positively correlated with the left cerebellum volume. Hyperactivity/impulsivity symptoms correlated negatively with the left inferior frontal orbital gyrus. Depression symptoms correlated negatively with the caudate (bilaterally) and positively with the right inferior parietal region. The groups did not differ regarding the FA values. Anxiety symptoms correlated positively with FA in corpus callosum and superior longitudinal fasciculus tracts. CONCLUSION: The present study showed neural correlates in regions related to functions, such as attention, executive control, and affective processing, suggesting that impairments in frontostriatal and frontoparietal-cerebellar areas observed in adults with ADHD persist into old age. Our findings reinforce the knowledge about ADHD in elderly, indicating an objective cognitive performance comparable to normal controls, a reduction of central symptoms, although maintaining a more impaired functionality and comorbidities

A esquizofrenia é um transtorno mental de alta complexidade e até o presente momento nenhuma teoria conseguiu explicar completamente sua etiologia. Uma dessas teorias acredita que a transferência de informações entre os hemisférios de pacientes com esquizofrenia, que ocorre através do corpo caloso, comissura anterior e posterior, pode estar comprometida. Os objetivos do nosso estudo foram avaliar se existem alterações de conectividade inter-hemisférica (IH) e se essas alterações sofrem influência do gênero, em pacientes portadores de esquizofrenia quando comparados com seus parentes em primeiro grau e controles saudáveis, utilizando-se da imagem de ressonância magnética por tensor de difusão (IRMTD). Participaram do estudo 30 pacientes portadores de esquizofrenia, diagnosticados pelos critérios do Manual diagnóstico e estatístico das doenças mentais em sua quarta edição, os quais foram selecionados entre os pacientes do grupo de medicações atípicas do ambulatório de esquizofrenia e da enfermaria psiquiátrica do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo; 30 parentes em primeiro grau desses pacientes; e 30 voluntários saudáveis. Todos os sujeitos do estudo foram submetidos a um exame de ressonância magnética, realizado no Centro de Ciências das Imagens e Física Médica de nossa instituição, onde foram adquiridas as sequências volumétricas e difusionais utilizadas em nosso estudo. Em posse das imagens de ressonância magnética dos 90 sujeitos do estudo, realizamos o pós-processamento dessas imagens, utilizando o software BrainVoyager QX® versão 2.4, com o intuito de obtermos, por meio dos dados provenientes da IRMTD, os mapas de anisotropia fracional (AF) e difusibilidade média (DM). Com esses mapas em mãos, procedemos à análise estatística do estudo, denominada de análise de covariância voxel a voxel (VANCOVA), no cérebro todo. Nessa análise, utilizamos a idade como covariável e verificamos a influência do gênero nos resultados encontrados. Nossos resultados 6 evidenciaram que os pacientes portadores de esquizofrenia apresentaram valores de AF e DM alterados em estruturas homólogas ao corpo caloso e áreas frontais adjacentes. Assim, podemos afirmar que descobrimos perda de conectividade IH nesses mesmos pacientes. Por meio de nosso estudo, descobrimos também a influência do gênero nos valores de AF e DM encontrados e então, consequentemente, podemos dizer que a conectividade IH de pacientes portadores de esquizofrenia sofreu influência do sexo. A idade também mostrou influenciar a conectividade IH de nossos pacientes. Com o atual conceito de que alterações de AF e DM podem ser encaradas como indicativos de comprometimento da mielina, e sabendo que a mielina participa diretamente das reações neuroquímicas do sistema glutamatérgico cerebral, também podemos dizer que o sistema glutamatérgico que participa da conectividade IH desses pacientes encontrava-se comprometido. / Schizophrenia is a highly complex mental disorder and no theory to date was able to fully explain the etiology of this disorder. One of the existing theories advocates that interhemispheric communication, which occurs through the corpus callosum and the anterior and posterior commissures, might be impaired in schizophrenia. Our study was designed to investigate whether there are interhemispheric connectivity (IC) alterations in schizophrenia and whether these alterations are influenced by gender through the comparison of schizophrenia patients with their first-degree relatives and healthy controls using diffusion tensor imaging (DTI). We enrolled 30 schizophrenia patients diagnosed according to the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders and selected from the Group of Atypical Medications of the Schizophrenia Outpatient Clinic and the psychiatric ward of the Ribeirão Preto Medical School University Hospital, 30 first-degree relatives of these patients and 30 healthy volunteers. All subjects underwent magnetic resonance imaging (MRI) scans for the acquisition of volumetric and diffusion sequences. The images were post-processed using BrainVoyager QX® version 2.4 to create fractional anisotropy (FA) and mean diffusivity (MD) maps from DTI data. The resulting data were analyzed using voxel-to- voxel analysis of covariance (VANCOVA) for the whole brain. In this analysis, we used age as a co-variable and assessed the influence of gender. Our results showed that schizophrenia patients had altered FA and MD values in structures homologous to the corpus callosum and adjacent frontal areas, suggestive of IC loss in the patients. We also found that gender influenced FA and MD values and, therefore, that IC in schizophrenia patients is influenced by gender. Age was also found to influence IC in our patients. Based on the current conception that FA and MD alterations may indicate myelin impairment and knowing that myelin participates directly in neurochemical reactions of the glutamatergic system in the brain, we can infer that the glutamatergic system, which is implicated in IC, is affected in schizophrenia and is influenced by gender.