Impaired Efficiency and Resilience of Structural Network in Spinocerebellar Ataxia Type 3

Background: Recent studies have shown that the patients with spinocerebellar ataxia type 3 (SCA3) may not only have disease involvement in the cerebellum and brainstem but also in the cerebral regions. However, the relations between the widespread degenerated brain regions remains incompletely explored.Methods: In the present study, we investigate the topological properties of the brain networks of SCA3 patients (n = 40) constructed based on the correlation of three-dimensional fractal dimension values. Random and targeted attacks were applied to measure the network resilience of normal and SCA3 groups.Results: The SCA3 networks had significantly smaller clustering coefficients (P < 0.05) and global efficiency (P < 0.05) but larger characteristic path length (P < 0.05) than the normal controls networks, implying loss of small-world features. Furthermore, the SCA3 patients were associated with reduced nodal betweenness (P < 0.001) in the left supplementary motor area, bilateral paracentral lobules, and right thalamus, indicating that the motor control circuit might be compromised.Conclusions: The SCA3 networks were more vulnerable to targeted attacks than the normal controls networks because of the effects of pathological topological organization. The SCA3 revealed a more sparsity and disrupted structural network with decreased values in the largest component size, mean degree, mean density, clustering coefficient, and global efficiency and increased value in characteristic path length. The cortico-cerebral circuits in SCA3 were disrupted and segregated into occipital-parietal (visual-spatial cognition) and frontal-pre-frontal (motor control) clusters. The cerebellum of SCA3 were segregated from cerebellum-temporal-frontal circuits and clustered into a frontal-temporal cluster (cognitive control). Therefore, the disrupted structural network presented in this study might reflect the clinical characteristics of SCA3

Doctor of Philosophy

dissertationNeurodegenerative diseases are an increasing health care problem in the United States. Quantitative neuroimaging provides a noninvasive method to illuminate individual variations in brain structure to better understand and diagnose these disorders. The overall objective of this research is to develop novel clinical tools that summarize and quantify changes in brain shape to not only help better understand age-appropriate changes but also, in the future, to dissociate structural changes associated with aging from those caused by dementing neurodegenerative disorders. Because the tools we will develop can be applied for individual assessment, achieving our goals could have a significant clinical impact. An accurate, practical objective summary measure of the brain pathology would augment current subjective visual interpretation of structural magnetic resonance images. Fractal dimension is a novel approach to image analysis that provides a quantitative measure of shape complexity describing the multiscale folding of the human cerebral cortex. Cerebral cortical folding reflects the complex underlying architectural features that evolve during brain development and degeneration including neuronal density, synaptic proliferation and loss, and gliosis. Building upon existing technology, we have developed innovative tools to compute global and local (voxel-wise and regional) cerebral cortical fractal dimensions and voxel-wise cortico-fractal surfaces from high-contrast MR images. Our previous research has shown that fractal dimension correlates with cognitive function and changes during the course of normal aging. We will now apply unbiased diffeomorphic atlasing methodology to dramatically improve the alignment of complex cortical surfaces. Our novel methods will create more accurate, detailed geometrically averaged images to take into account the intragroup differences and make statistical inferences about spatiotemporal changes in shape of the cerebral cortex across the adult human lifespan

Cortical complexity as a measure of age-related brain atrophy

The structure of the human brain changes in a variety of ways as we age. While a sizeable literature has examined age-related differences in cortical thickness, and to a lesser degree, gyrification, here we examined differences in cortical complexity, as indexed by fractal dimensionality in a sample of over 400 individuals across the adult lifespan. While prior studies have shown differences in fractal dimensionality between patient populations and age-matched, healthy controls, it is unclear how well this measure would relate to age-related cortical atrophy. Initially computing a single measure for the entire cortical ribbon, i.e., unparcellated gray matter, we found fractal dimensionality to be more sensitive to age-related differences than either cortical thickness or gyrification index. We additionally observed regional differences in age-related atrophy between the three measures, suggesting that they may index distinct differences in cortical structure. We also provide a freely available MATLAB toolbox for calculating fractal dimensionality

Predicting age from cortical structure across the lifespan

Despite inter-individual differences in cortical structure, cross-sectional and longitudinal studies have demonstrated a large degree of population-level consistency in age-related differences in brain morphology. The present study assessed how accurately an individual’s age could be predicted by estimates of cortical morphology, comparing a variety of structural measures, including thickness, gyrification, and fractal dimensionality. Structural measures were calculated across up to seven different parcellation approaches, ranging from 1 region to 1000 regions. The age-prediction framework was trained using morphological measures obtained from T1-weighted MRI volumes collected from multiple sites, yielding a training dataset of 1056 healthy adults, aged 18-97. Age predictions were calculated using a machine-learning approach that incorporated non-linear differences over the lifespan. In two independent, held-out test samples, age predictions had a median error of 6-7 years. Age predictions were best when using a combination of cortical metrics, both thickness and fractal dimensionality. Overall, the results reveal that age-related differences in brain structure are systematic enough to enable reliable age prediction based on metrics of cortical morphology

Computational Intelligence in Electromyography Analysis

Electromyography (EMG) is a technique for evaluating and recording the electrical activity produced by skeletal muscles. EMG may be used clinically for the diagnosis of neuromuscular problems and for assessing biomechanical and motor control deficits and other functional disorders. Furthermore, it can be used as a control signal for interfacing with orthotic and/or prosthetic devices or other rehabilitation assists. This book presents an updated overview of signal processing applications and recent developments in EMG from a number of diverse aspects and various applications in clinical and experimental research. It will provide readers with a detailed introduction to EMG signal processing techniques and applications, while presenting several new results and explanation of existing algorithms. This book is organized into 18 chapters, covering the current theoretical and practical approaches of EMG research

Quantitative MR Image Analysis - a Useful Tool in Differentiating Glioblastoma from Solitary Brain Metastasis

Cilj: Prikaz glioblastoma i metastaza na konvencionalnom MRI je često jako sličan, ali se terapijski pristup i prognoza bitno razlikuju. Čak i primenom naprednih MR tehnika, u nekim slučajevima dijagnoza ostaje nejasna. Glavni cilj disertacije bio je da utvrdi da li fraktalna ili teksturna, ili obe kvantitativne analize MR slike mogu doprineti diferencijaciji glioblastoma od solitarne metastaze mozga. Metod: Studija je sprovedena na ukupno 96 pacijenata sa dokazanim dijagnozama glioblastoma (50 pacijenata), odnosno solitarne metastaze (46 pacijenata). Izdvojene su slike sa najinformativnijim prikazom lezije (jedan isti presek u tri različite sekvence: CET1, T2 i SWI), a zatim je učinjena njihova kompjuterska analiza, primenom fraktalne metode brojanja kvadrata i teksturne metode bazirane na matrici zajedničke pojave istog nivoa sive boje (GLCM). Rezultati: Analizom sive skale celog tumora i binarne slike unutrašnjosti tumora sa T2 sekvence dobijen je najveći broj parametara koji značajno razlikuju dve vrste tumora (drugi ugaoni moment SASM, inverzni moment razlike SIDM, kontrast SCON, korelacija SCOR, diferencijalna fraktalna dimenzija DDIFF, odnosno binarna fraktalna dimenzija unutrašnjosti DBIN2, normirana fraktalna dimenzija DNORM, lakunarnost Ʌ2), dok su se druge dve sekvence (CET1 i SWI) pokazale manje pogodnim za kvantifikaciju. Kombinacijom parametara povećala se tačnost testiranja (AUC 0,838±0,041, senzitivnost 78% i specifičnost 76% za kombinaciju SASM i SIDM sa CET1 i T2 + SASM sa SWI + DBIN2 i DNORM sa T2). Zaključak: Kvantifikacija MR slike može doprineti diferencijalno dijagnostičkoj odluci između glioblastoma i solitarne metastaze mozga i potencijalno može postati deo svakodnevne radiološke prakse.Purpose: Presentation of glioblastomas and metastases on conventional MRI is quite similar, however treatment strategy and prognosis are substantially different. Even with advanced MR techniques, in some cases diagnostic uncertainty remains. The main objective of dissertation was to determine whether fractal, texture, or both quantitative MR image analysis could aid in differentiating glioblastoma from solitary brain metastasis. Method: Study embraced 96 patients with proven diagnosis of glioblastoma (50 patients), respectively solitary metastasis (46 patients). Images with the most representative lesion (one same slice on three different sequences: CET1, T2 and SWI) were selected, and computer analysis was done by fractal box-counting and texture gray level co-occurrence matrix (GLCM) methods. Results: Gray scale analysis of whole tumor and binary image analysis of tumor´s inner structures, both derived on T2 sequence, obtained the most significantly different parameters between two types of tumors (angular second moment SASM, inverse difference moment SIDM, contrast SCON, correlation SCOR, differential box dimension DDIFF, respectively binary box dimension DBIN2, normalized box dimension DNORM, lacunarity Ʌ2), while the other two sequences (CET1 and SWI) showed less suitable for quantification. The combinations of parameters yielded better results (AUC-0.838±0.041, sensitivity 78% and specificity 76% for next combination SASM and SIDM from CET1 and T2 + SASM from SWI + DBIN2 and DNORM from T2). Conclusions: MR image quantification may aid in differentiation between glioblastoma and solitary brain metastasis, and potentially could become a part of daily radiology practice