Neuroimaging in Alzheimer's disease: current role in clinical practice and potential future applications

Alzheimer's disease is the most common cause of dementia and its prevalence is expected to increase in the coming years. Therefore, accurate diagnosis is crucial for patients, clinicians and researchers. Neuroimaging techniques have provided invaluable information about Alzheimer's disease and, owing to recent advances, these methods will have an increasingly important role in research and clinical practice. The purpose of this article is to review recent neuroimaging studies of Alzheimer's disease that provide relevant information to clinical practice, including a new modality: in vivo amyloid imaging. Magnetic resonance imaging, single photon emission computed tomography and 18F-fluorodeoxyglucose-positron emission tomography are currently available for clinical use. Patients with suspected Alzheimer's disease are commonly investigated with magnetic resonance imaging because it provides detailed images of brain structure and allows the identification of supportive features for the diagnosis. Neurofunctional techniques such as single photon emission computed tomography and 18F-fluorodeoxyglucose-positron emission tomography can also be used to complement the diagnostic investigation in cases of uncertainty. Amyloid imaging is a non-invasive technique that uses positron emission tomography technology to investigate the accumulation of the β-amyloid peptide in the brain, which is a hallmark of Alzheimer's disease. This is a promising test but currently its use is restricted to very few specialized research centers in the world. Technological innovations will probably increase its availability and reliability, which are the necessary steps to achieve robust clinical applicability. Thus, in the future it is likely that amyloid imaging techniques will be used in the clinical evaluation of patients with Alzheimer's disease

Assimilating knowledge from neuroimages in schizophrenia diagnostics

The aim of this article is to propose an integrated framework for classifying and describing patterns of disorders from medical images using a combination of image registration, linear discriminant analysis and region-based ontologies. In a first stage of this endeavour we are going to study and evaluate multivariate statistical methodologies to identify the most discriminating hyperplane separating two populations contained in the input data. This step has, as its major goal, the analysis of all the data simultaneously rather than feature by feature. The second stage of this work includes the development of an ontology whose aim is the assimilation and exploration of the knowledge contained in the results of the previous statistical methods. Automated knowledge discovery from images is the key motivation for the methods to be investigated in this research. We argue that such investigation provides a suitable framework for characterising the high complexity of MR images in schizophrenia

SPECT and PET in Eating Disorders

Medical imaging techniques like PET and SPECT have been applied for investigation of brain function in anorexia and bulimia nervosa. Regional abnormalities have been detected in cerebral blood flow, glucose metabolism, the availability of several neurotransmitter receptors (serotonin 1A and 2A, dopamine D2/D3, histamine H1, mu-opioid, GABA(A)-benzodiazepine, and cannabinoid CB1), stimulant-induced dopamine release, presynaptic FDOPA influx, and the density of serotonin transporters. Different subtypes of eating disorders appear to be associated with specific functional changes. It is hard to judge whether such changes are a consequence of chronic dietary restrictions or are caused by a putative anorexia (or bulimia) nervosa endophenotype. Many abnormalities (particularly those of glucose metabolism) appear to be reversible after restoration of weight or normal patterns of food intake and may represent consequences of purging or starvation. However, some changes of regional flow and neurotransmitter systems persist even after successful therapy which suggests that these reflect traits that are independent of the state of the illness. Changes of the serotonergic system (altered activity of 5-HT1A and 5-HT2A receptors and 5-HT transporters) may contribute to dysregulation of appetite, mood, and impulse control in eating disorders and may represent a trait which predisposes to the development of anxiety, obsessionality, and behavioral inhibition. Assessment of functional changes in the brain with PET or SPECT may have prognostic value and predict neuropsychological status after several years of therapy

Learning and memory and its relationship with the lateralization of epileptic focus in subjects with temporal lobe epilepsy

Background : In medial temporal lobe epilepsy (MTLE), previous studies addressing the hemispheric laterality of epileptogenic focus and its relationship with learning and memory processes have reported controversial findings. Objective : To compare the performance of MTLE patients according to the location of the epileptogenic focus on the left (MTLEL) or right temporal lobe (MTLER) on tasks of episodic learning and memory for verbal and visual content. Methods : One hundred patients with MTLEL and one hundred patients with MTLER were tested with the following tasks: the Rey Auditory Verbal Learning Test (RAVLT) and the Logical Memory-WMS-R to evaluate verbal learning and memory; and the Rey Visual Design Learning Test (RVDLT) and the Visual Reproduction-WMS-R to evaluate visual learning and memory. Results : The MTLEL sample showed significantly worse performance on the RAVLT (p < 0.005) and on the Logical Memory tests (p < 0.01) than MTLER subjects. However, there were no significant between-group differences in regard to the visual memory tests. Discussion : Our findings suggest that verbal learning and memory abilities are dependent on the structural and functional integrity of the left temporal lobe, while visual abilities are less dependent on the right temporal lobe.Contexto : Estudos anteriores abordando a lateralidade hemisférica de foco epiléptico na epilepsia do lobo temporal mesial (ELTM) e sua relação com os processos de aprendizagem e memória têm relatado resultados controversos. Objetivo : Comparar o desempenho de pacientes com ELTM de acordo com a localização do foco epiléptico à esquerda (ELTME) ou à direita (ELTMD) em tarefas de aprendizagem e memória episódica para conteúdo verbal e visual. Métodos: Cem pacientes com ELTME e cem pacientes com ELTMD foram avaliados com os seguintes testes: Teste de Aprendizagem Auditiva Verbal de Rey (RAVLT) e Memória Lógica – WMS-R para avaliar aprendizagem e memória verbal e o Teste de Aprendizagem Visual para Desenhos de Rey (RVDLT) e Reprodução Visual – WMS-R para avaliar a aprendizagem e memória visual. Resultados : A amostra com ELTME mostrou desempenho significativamente pior no RAVLT (p < 0,005) e na Memória Lógica (p < 0,01) em comparação aos indivíduos ELTMD. No entanto, não houve diferenças significativas entre os grupos no que diz respeito aos testes de aprendizagem e memória visual. Conclusão : Nossos resultados sugerem que a aprendizagem e a memória verbais são dependentes da integridade estrutural e funcional do lobo temporal esquerdo, enquanto as capacidades de aprendizagem e memória visual são menos dependentes do lobo temporal direito

Voxel-based investigations of regional cerebral blood flow abnormalities in Alzheimer's disease using a single-detector SPECT system

PURPOSE: To evaluate the feasibility of using the Statistical Parametric Mapping (SPM) program for an automated, voxel-by-voxel assessment of regional cerebral blood flow (rCBF) deficits in Alzheimer's disease (AD) subjects relative to age-matched controls studied with a conventional, single-detector SPECT system. METHODS: We used a databank of 99mTc-HMPAO images of 19 patients with a diagnosis of probable AD and 15 elderly healthy volunteers; data were acquired using an Orbiter-Siemens single-detector SPECT system. Using SPM, images were transformed spatially, smoothed (12mm), and the data were compared on a voxel-by-voxel basis with t-tests. RESULTS: There were significant rCBF reductions in AD patients relative to controls involving regions predicted a priori to be affected in AD, namely the left temporal and parietal neocortices, and the right posterior cingulate gyrus (pOBJETIVO: Avaliar a viabilidade de emprego do programa Statistical Parametric Mapping (SPM) para investigar de forma automatizada, voxel-a-voxel, a presença de déficits de fluxo sanguíneo cerebral regional (FSCr) em pacientes com doença de Alzheimer (DA) comparados a sujeitos-controle pareados para idade, usando imagens de SPECT adquiridas com um equipamento convencional de detector único. MÉTODOS: Foi utilizado um banco de imagens adquiridas após injeção de 99mTc-HMPAO em 19 pacientes com diagnóstico provável de DA e 15 voluntários idosos saudáveis, usando um equipamento de SPECT Orbiter-Siemens de detector único. Empregando o programa SPM, as imagens foram transformadas espacialmente, suavizadas (12mm FWHM), e comparadas estatisticamente voxel-a-voxel entre os dois grupos, usando o teste de T. RESULTADOS: Foram identificadas reduções significativas de FSCr nos pacientes com DA comparados aos controles em regiões previstas a priori como afetadas por esta forma de demência, quais sejam os neocórtices temporal e parietal em hemisfério esquerdo e o cíngulo posterior direito (p<0,05, corrigido para comparações múltiplas). DISCUSSÃO: A localização dos focos de redução de FSCr em pacientes com DA no nosso estudo é, de forma geral, consistente com os achados de déficits cerebrais detectados em estudos anteriores de neuroimagem funcional na DA realizados com equipamentos de resolução espacial mais alta. Isto sugere o potencial de utilidade do programa SPM para a análise de dados de SPECT adquiridos com equipamentos de detector único, apesar da sensibilidade e resolução espacial limitadas de tais aparelhos

Voxel-based investigations of regional cerebral blood flow abnormalities in Alzheimer's disease using a single-detector SPECT system

PURPOSE: To evaluate the feasibility of using the Statistical Parametric Mapping (SPM) program for an automated, voxel-by-voxel assessment of regional cerebral blood flow (rCBF) deficits in Alzheimer's disease (AD) subjects relative to age-matched controls studied with a conventional, single-detector SPECT system. METHODS: We used a databank of 99mTc-HMPAO images of 19 patients with a diagnosis of probable AD and 15 elderly healthy volunteers; data were acquired using an Orbiter-Siemens single-detector SPECT system. Using SPM, images were transformed spatially, smoothed (12mm), and the data were compared on a voxel-by-voxel basis with t-tests. RESULTS: There were significant rCBF reductions in AD patients relative to controls involving regions predicted a priori to be affected in AD, namely the left temporal and parietal neocortices, and the right posterior cingulate gyrus (pOBJETIVO: Avaliar a viabilidade de emprego do programa Statistical Parametric Mapping (SPM) para investigar de forma automatizada, voxel-a-voxel, a presença de déficits de fluxo sanguíneo cerebral regional (FSCr) em pacientes com doença de Alzheimer (DA) comparados a sujeitos-controle pareados para idade, usando imagens de SPECT adquiridas com um equipamento convencional de detector único. MÉTODOS: Foi utilizado um banco de imagens adquiridas após injeção de 99mTc-HMPAO em 19 pacientes com diagnóstico provável de DA e 15 voluntários idosos saudáveis, usando um equipamento de SPECT Orbiter-Siemens de detector único. Empregando o programa SPM, as imagens foram transformadas espacialmente, suavizadas (12mm FWHM), e comparadas estatisticamente voxel-a-voxel entre os dois grupos, usando o teste de T. RESULTADOS: Foram identificadas reduções significativas de FSCr nos pacientes com DA comparados aos controles em regiões previstas a priori como afetadas por esta forma de demência, quais sejam os neocórtices temporal e parietal em hemisfério esquerdo e o cíngulo posterior direito (

Diagnosis of Regional Cerebral Blood Flow Abnormalities Using Spect: Agreement between Individualized Statistical Parametric Maps and Visual Inspection by Nuclear Medicine Physicians with Different Levels of Expertise in Nuclear Neurology

INTRODUCTION: Visual analysis is widely used to interpret regional cerebral blood flow (rCBF) SPECT images in clinical practice despite its limitations. Automated methods are employed to investigate between-group rCBF differences in research studies but have rarely been explored in individual analyses. OBJECTIVES: To compare visual inspection by nuclear physicians with the automated statistical parametric mapping program using a SPECT dataset of patients with neurological disorders and normal control images. METHODS: Using statistical parametric mapping, 14 SPECT images from patients with various neurological disorders were compared individually with a databank of 32 normal images using a statistical threshold of p<0.05 (corrected for multiple comparisons at the level of individual voxels or clusters). Statistical parametric mapping results were compared with visual analyses by a nuclear physician highly experienced in neurology (A) as well as a nuclear physician with a general background of experience (B) who independently classified images as normal or altered, and determined the location of changes and the severity. RESULTS: Of the 32 images of the normal databank, 4 generated maps showing rCBF abnormalities (p<0.05, corrected). Among the 14 images from patients with neurological disorders, 13 showed rCBF alterations. Statistical parametric mapping and physician A completely agreed on 84.37% and 64.28% of cases from the normal databank and neurological disorders, respectively. The agreement between statistical parametric mapping and ratings of physician B were lower (71.18% and 35.71%, respectively). CONCLUSION: Statistical parametric mapping replicated the findings described by the more experienced nuclear physician. This finding suggests that automated methods for individually analyzing rCBF SPECT images may be a valuable resource to complement visual inspection in clinical practice

Diagnosis of regional cerebral blood flow abnormalities using SPECT: agreement between individualized statistical parametric maps and visual inspection by nuclear medicine physicians with different levels of expertise in nuclear neurology

INTRODUCTION: Visual analysis is widely used to interpret regional cerebral blood flow (rCBF) SPECT images in clinical practice despite its limitations. Automated methods are employed to investigate between-group rCBF differences in research studies but have rarely been explored in individual analyses. OBJECTIVES: To compare visual inspection by nuclear physicians with the automated statistical parametric mapping program using a SPECT dataset of patients with neurological disorders and normal control images. METHODS: Using statistical parametric mapping, 14 SPECT images from patients with various neurological disorders were compared individually with a databank of 32 normal images using a statistical threshold of