Hippocampal Automatic Recognition and 3D Segmentation Based on Active Appearance Model in Brain MR Images for Early Diagnosis ofAlzheimer's Disease

目的:研究磁共振(MAgnETIC rESOnAnCE,Mr)脑图像中海马的自动分割方法及海马的形态学分析方法,为阿尔茨海默病(AlzHEIMEr'S dISEASE,Ad)的早期诊断提供依据。方法:对20例Ad患者和60名正常对照者行MrI T1 WI 3d容积扫描,建立海马的三维主动表观模型,并以此模型对每个个体脑部磁共振图像上的海马进行自动识别和三维分割,分别建立正常对照组和Ad组的海马统计形状模型,比较Ad组与正常对照组间海马形状的差异性。结果:海马三维分割方法与手动分割方法在海马体积测量上无统计学差别(P>0.05);Ad患者海马头部发生萎缩(P0.05).Hippocampal head atrophy was found in AD patients(P<0.05).Conclusions: Hippocampal three-dimensional segmentation and automatic identification method based on active appearance model in brain MR image is accurate and reliable;the feature of hippocampal head atrophy can be used as a basis for diagnosis of AD.哈尔滨医科大学研究生创新基金(HCXB2010019);国家自然科学基金(81071219

Hippocampal Automatic Recognition and 3D Segmentation Based on Active Appearance Model in Brain MR Images for Early Diagnosis ofAlzheimer's Disease

目的:研究磁共振(MAgnETIC rESOnAnCE,Mr)脑图像中海马的自动分割方法及海马的形态学分析方法,为阿尔茨海默病(AlzHEIMEr'S dISEASE,Ad)的早期诊断提供依据。方法:对20例Ad患者和60名正常对照者行MrI T1 WI 3d容积扫描,建立海马的三维主动表观模型,并以此模型对每个个体脑部磁共振图像上的海马进行自动识别和三维分割,分别建立正常对照组和Ad组的海马统计形状模型,比较Ad组与正常对照组间海马形状的差异性。结果:海马三维分割方法与手动分割方法在海马体积测量上无统计学差别(P>0.05);Ad患者海马头部发生萎缩(P0.05).Hippocampal head atrophy was found in AD patients(P<0.05).Conclusions: Hippocampal three-dimensional segmentation and automatic identification method based on active appearance model in brain MR image is accurate and reliable;the feature of hippocampal head atrophy can be used as a basis for diagnosis of AD.哈尔滨医科大学研究生创新基金(HCXB2010019);国家自然科学基金(81071219

Desarrollo y evaluación de una herramienta de registro difeomórfico por landmarks 3D de estructuras cerebrales en imágenes MRI

En la disciplina de Anatomía Computacional se requiere una herramienta de registro o normalización espacial de imágenes que sea capaz de modelar grandes deformaciones (ya que existe gran variabilidad anatómica entre los cerebros humanos, especialmente en la corteza) garantizando suavidad en las transformaciones espaciales. Con este fin, recientemente se ha propuesto el paradigma de los difeomorsmos, tanto en imágenes volumétricas como en registro de puntos anatómicos o landmarks. Este proyecto versa sobre el registro difeomórco de estructuras cerebrales mediante landmarks 3D a partir de imágenes de resonancia magnética. El objetivo final consiste en desarrollar y evaluar las prestaciones de una herramienta que proporcione una transformación espacial que consiga una correspondencia entre los surcos y giros más importantes de la corteza cerebral. En concreto, se trata de un problema de registro no rígido basado en una transformación difeomórca entre los puntos de un atlas cerebral (imagen y sus correspondientes etiquetas de segmentación) y los puntos de unas imágenes objetivo. Dicha transformación se ha utilizado además como inicialización de una herramienta ya existente de registro volumétrico de todo el cerebro, con el objetivo de dotarla de mayor robustez. La evaluación de prestaciones se ha realizado sobre un conjunto de imágenes MRI provenientes del estudio Alzheimer's Disease Neuroimaging Initiative (ADNI). Los puntos anatómicos se han obtenido mediante la herramienta BrainVisa. Aunque estos landmarks son realmente tridimensionales, a lo largo de esta memoria y por simplicidad en la visualización de los resultados, se presentan en dos dimensiones para un corte axial representativo. Los créditos prácticos se han realizado en el Servicio de Radiodiagnóstico del Grupo Hospitalario Quirón, Zaragoza, bajo la tutela del Jefe de Servicio, el Dr. Nicolás Fayed Miguel. El objetivo fue conocer el equipamiento de radiología (resonancia magnética nuclear, tomografía computerizada, ecografías, rayos X, etc.) así como el sistema PACS de transferencia, gestión y almacenamiento de imágenes médicas

Hippocampus and Amygdala subfields in 7Tesla magnetic resonance imaging as biomarkers of Alzheimer's dementia and for memory performance prediction

Hintergrund: Ein Therapiebeginn in frühen Stadien der Alzheimer Demenz (AD), zum Beispiel bei noch unauffälliger Kognition, könnte die Progression ins Krankheitsstadium möglicherweise verhindern. Voraussetzung dafür sind Biomarker zur Identifizierung von Risikopersonen für die Entwicklung einer AD, wie Personen mit subjektiver kognitiver Verschlechterung (englisch (engl.) Subjective Cognitive Decline, SCD) und leichter kognitiver Beeinträchtigung (engl. Mild Cognitive Impairment, MCI). Volumetrische Analysen in der nicht invasiven Magnetresonanztomographie (MRT) der Standardmarker Hippocampus und Großhirnkortex brachten dabei eingeschränkte Erfolge. Da im hochauflösenden 7Tesla (T) MRT auch kleinere Regionen hochwertig segmentiert werden können, war Ziel dieser Arbeit, die hippocampale Molekularschicht und die Amygdala mit Kernen im AD-Kontinuum zu analysieren und mit den Volumen-Standardmarkern zu vergleichen. Methoden: Es wurden 27 gesunde Teilnehmende (engl. Healthy Control, HC), 33 SCD, 26 MCI und 26 AD Teilnehmende in diese Studie eingeschlossen. Die Gedächtnisleistung wurde bei Erstvisite (N = 112), nach ein (N = 69) und drei (N = 40) Jahren anhand eines zusammengesetzten Gedächtnisscores gemessen. Bei Erstvisite wurden hochauflösende 7T MRT Bilder angefertigt, die Volumina automatisch und atlas-basiert segmentiert und auf das totale intrakranielle Volumen adjustiert. Die Volumina wurden, mit Adjustierung auf Alter, Bildung und Geschlecht, auf einen Zusammenhang mit der Diagnose sowie der Gedächtnisleistung geprüft. Mit linearen gemischten Modellen wurde die prognostische Aussagekraft der Volumina auf die Entwicklung des Gedächtnisses in den nächsten drei Jahren evaluiert. Ergebnisse: Bei der Amygdala und einigen Kernen zeigte sich im Vergleich zu HC eine deutliche Reduktion der Volumina bei SCD (Volumenunterschied -9% – -10%), MCI (-11% – -20%) und AD (-18% – -32%). Die Differenz zwischen HC und SCD konnte beim Hippocampus, hippocampalen Subregionen, Molekularschicht sowie kortikalen Volumina nicht nachgewiesen werden ( 55% Varianzerklärung). Die prognostische Aussagekraft durch die Volumina war allerdings geringer als jene, die bereits von den vier Diagnose-Gruppen ausging (R² = 77% Varianzerklärung). Fazit: Die Arbeit lieferte erste Hinweise, dass die Volumina der Amygdala und ihrer Kerne eine MRT-gestützte Diagnosestellung des Risikostadiums SCD ermöglichen könnten. Zudem gab es Zeichen, dass Volumina von Hippocampus, Amygdala und deren Subregionen bei der Prognosestellung künftiger Gedächtnisleistung hilfreich sein könnten, vor allem bei unbekannter Diagnose.Background: Starting therapy in the early stages of Alzheimer's disease (AD), for example when cognition is still unaffected, could probably prevent progression to the dementia stage. This requires biomarkers to identify individuals at risk for developing AD, such as those with Subjective Cognitive Decline (SCD) and Mild Cognitive Impairment (MCI). Volumetric analysis in noninvasive magnetic resonance imaging (MRI) of the standard markers Hippocampus and cerebral cortex yielded limited success in identifying these risk stages. Since smaller regions can be segmented with high quality in high-resolution 7Tesla MRI, the aim of this work was to analyze the hippocampal molecular layer and the Amygdala with their nuclei in the AD spectrum and to compare them with volumetric standard markers. Methods: 27 healthy control (HC), 33 SCD, 26 MCI, and 26 AD participants were included in this study. Memory performance was measured at baseline (N = 112), after one (N = 69), and three (N = 40) years using a composite memory score. At baseline, high-resolution 7T MRI images were acquired, Hippocampus, Amygdala, each of their subregions, and cortical volumes was segmented automatically and atlas-based and adjusted for total intracranial volume. Volumes were analyzed, with adjustment for age, education, and sex, for association with diagnosis as well as memory performance. Linear Mixed Models were used to evaluate the predictive effects of volumes on future memory performance over the next three years. Results: In the Amygdala and some nuclei, compared with HC a significant reduction in volumes in SCD (volume difference -9% – -10%), MCI (-11% – -20%) and AD (-18% – -32%) was found. The difference between HC and SCD was not detected in the Hippocampus, hippocampal subregions, molecular layer, and cerebral cortex ( 55% explanation of variance). However, the prognostic significance provided by the volumes was lower than that provided by the four diagnostic groups (R² = 77.3% explanation of variance). Conclusion: This study provided the first evidence that volumes of the Amygdala and its nuclei could support MRI-based diagnosis of the SCD risk stage. In addition, evidence was found that the Hippocampus and Amygdala volumes and their subregions may be useful in predicting future memory performance, especially when the individual's diagnosis is unknown

Blood Glucose Levels and Genetic Factors as Predictors of Neurocognitive Outcomes

Alzheimer’s disease (AD), a neurodegenerative disease characterized by progressive cognitive decline, is becoming increasingly prevalent as the population ages. There is no effective treatment for AD, so manipulating modifiable risk factors before clinical symptoms of dementia develop may be the most effective course to prevent, delay, or modify the course of AD. Type II diabetes mellitus (DM), characterized by hyperglycemia and insulin resistance, affects over a quarter of older adults and has been linked with AD, cognitive decline, and brain atrophy. Because DM is preventable and treatable, it represents an intervention target for AD. This dissertation investigated the association between glucose levels and three outcomes – performance on a battery of cognitive tests over time, time to symptom onset of mild cognitive impairment (MCI) or dementia, and cortical thickness in AD-signature regions (i.e., entorhinal cortex, inferior temporal gyrus, parahippocampal gyrus pars triangularis, precuneus, superior frontal and parietal gyri, supramarginal gyrus, and temporal pole). Additionally, it investigated how two genes – apolipoprotein E (APOE) and translocase of the outer mitochondrial membrane (TOMM) 40 – may modify the relationship between glucose and these outcomes. Both the APOE ε4 allele and the TOMM40 very long/very long (VL/VL) genotype (versus the short/short (S/S) genotype) have been associated with increased risk of dementia, cognitive decline, and brain atrophy, and some evidence suggests that these genetic factors may further increase the risk in individuals with DM. This research was conducted using data from the BIOCARD Study (n=349), which enrolled primarily middle-aged individuals, three-quarters of whom had a first-degree relative with dementia. The goal of the study was to examine the early signs and symptoms of AD in a high-risk cohort. For this dissertation, baseline blood glucose level, which was ascertained from a blood draw in a clinical exam, was the primary predictor and was available for 333 participants. APOE and TOMM40 genotypes were also determined from blood samples. Age of MCI or dementia symptom onset was determined through consensus diagnosis. At annual visits, participants completed a neuropsychological test battery, and at baseline and bi-annually, participants completed magnetic resonance imaging (MRI) scans. The first paper in this study used linear mixed effects models (LMMs) and generalized estimating equation (GEE) models to investigate the association between glucose and cognitive performance over time. We used confirmatory factor analysis (CFA) to create one factor based on performance on tests of executive function (the executive function factor) and one factor based on performance on tests of memory (the memory factor). We found that higher baseline glucose was associated with greater decline on the executive function factor score in both LMMs (B=-0.005; 95% CI -0.008, -0.001) and GEE models (B=-0.004; 95% CI -0.007, -0.001) that controlled for age, sex, race, education, depression, and medical conditions (i.e., cardiovascular conditions, hypertension, hypercholesterolemia, traumatic brain injury (TBI)). Interaction analyses using LMMs found that higher glucose was associated with significant decline in executive function score in ε4 carriers (B=-0.013; 95% CI -0.020, -0.006), but not in non-carriers (B=-0.002, 95% CI -0.006, 0.002). In LMMs, higher glucose was also associated with poorer memory factor score over time in subjects with the S/S genotype (B=-0.013; 95% CI -0.024, -0.002), versus the VL/VL genotype (B=0.004; 95% CI -0.003, 0.010). The second paper in this study used Cox proportional hazard models to investigate the association between baseline blood glucose level and time to MCI or dementia symptom onset, as well as the association between the interaction of APOE and glucose and TOMM40 and glucose and time to symptom onset. We did not find an association between glucose level and time to symptom onset; additionally, we did not find that APOE or TOMM40 modified this relationship. In the final paper, linear regression analyses showed that glucose level was associated with reduced cortical thickness in the parahippocampal gyrus (B=-0.002; 95% CI -0.003, -0.0001) and temporal pole (B=-0.002; 95% CI -0.003, -0.0002) in a fully-adjusted model. Additionally, higher glucose levels were associated with thinner measures of the superior parietal gyri (B=-0.001; 95% CI -0.002, 0.0005 vs. B=0.0007; 95% CI 3.05e-6, 0.001) and temporal pole (B=-0.004; 95% CI -0.008, -0.0009 vs. B=-0.0003; 95% CI -0.002, 0.001) in ε4 allele carriers versus non-carriers. This evidence suggests that even in middle-aged, cognitively healthy samples, higher levels of glucose, even in those without DM, can negatively impact cognitive performance and cortical thickness. Maintaining normal blood glucose levels may be important in middle age for reducing risk of cognitive decline, AD, and brain atrophy

Regional shape abnormalities in mild cognitive impairment and Alzheimer's disease

10.1016/j.neuroimage.2009.01.013NeuroImage453656-661NEIM