Probable 4-Repeat Tauopathy Criteria Predict Brain Amyloid Negativity, Distinct Clinical Features, and FDG-PET/MRI Neurodegeneneration Patterns in Corticobasal Syndrome.

BACKGROUND: Corticobasal syndrome (CBS) is associated with diverse underlying pathologies, including the four-repeat (4R)-tauopathies. The Movement Disorders Society (MDS) criteria for progressive supranuclear palsy (PSP) proposed the novel category "probable 4R-tauopathy" to address the phenotypic overlap between PSP and corticobasal degeneration (CBD). OBJECTIVES: To investigate the clinical ability of the MDS-PSP criteria for probable 4R-tauopathy in predicting a negative amyloid-PET in CBS. Additionally, this study aims to explore CBS patients classified as 4R-tauopathy concerning their clinical features and neuroimaging degeneration patterns. METHODS: Thirty-two patients with probable CBS were prospectively evaluated and split into those who fulfilled or did not fulfill the 4R-tauopathy criteria (CBS-4RT+ vs. CBS-4RT-). All patients underwent positron emission tomographies (PET) with [18 F]fluorodeoxyglucose and [11 C]Pittsburgh Compound-B (PIB) on a hybrid PET-MRI scanner to perform multimodal quantitative comparisons with a control group. RESULTS: Eleven patients were clinically classified as CBS-4RT+, and only one had a positive PIB-PET. The CBS-4RT+ classification had 92% specificity, 52% sensitivity, and 69% accuracy in predicting a negative PIB-PET. The CBS-4RT+ group presented with dysarthria and perseveration more often than the CBS-4RT- group. Moreover, the CBS-4RT+ group showed a prominent frontal hypometabolism extending to the supplementary motor area and striatum, and brain atrophy at the anterior cingulate and bilateral striata. CONCLUSIONS: The 4R-tauopathy criteria were highly specific in predicting a negative amyloid-PET in CBS. Patients classified as 4R-tauopathy presented distinct clinical aspects, as well as brain metabolism and atrophy patterns previously associated with tauopathies.

Evaluation of 10-minute post-injection 11C-PiB PET and its correlation with 18F-FDG PET in older adults who are cognitively healthy, mildly impaired, or with probable Alzheimer's disease.

OBJECTIVE: Positron emission tomography (PET) allows in vivo evaluation of molecular targets in neurodegenerative diseases, such as Alzheimer's disease. Mild cognitive impairment is an intermediate stage between normal cognition and Alzheimer-type dementia. In vivo fibrillar amyloid-beta can be detected in PET using [11C]-labeled Pittsburgh compound B (11C-PiB). In contrast, [18F]fluoro-2-deoxy-d-glucose (18F-FDG) is a neurodegeneration biomarker used to evaluate cerebral glucose metabolism, indicating neuronal injury and synaptic dysfunction. In addition, early cerebral uptake of amyloid-PET tracers can determine regional cerebral blood flow. The present study compared early-phase 11C-PiB and 18F-FDG in older adults without cognitive impairment, amnestic mild cognitive impairment, and clinical diagnosis of probable Alzheimer's disease. METHODS: We selected 90 older adults, clinically classified as healthy controls, with amnestic mild cognitive impairment, or with probable Alzheimer's disease, who underwent an 18F-FDG PET, early-phase 11C-PiB PET and magnetic resonance imaging. All participants were also classified as amyloid-positive or -negative in late-phase 11C-PiB. The data were analyzed using statistical parametric mapping. RESULTS: We found that the probable Alzheimer's disease and amnestic mild cognitive impairment group had lower early-phase 11C-PiB uptake in limbic structures than 18F-FDG uptake. The images showed significant interactions between amyloid-beta status (negative or positive). However, early-phase 11C-PiB appears to provide different information from 18F-FDG about neurodegeneration. CONCLUSIONS: Our study suggests that early-phase 11C-PiB uptake correlates with 18F-FDG, irrespective of the particular amyloid-beta status. In addition, we observed distinct regional distribution patterns between both biomarkers, reinforcing the need for more robust studies to investigate the real clinical value of early-phase amyloid-PET imaging.

Evaluation of 10-minute post-injection 11C-PiB PET and its correlation with 18F-FDG PET in older adults who are cognitively healthy, mildly impaired, or with probable Alzheimer's disease

Objective: Positron emission tomography (PET) allows in vivo evaluation of molecular targets in neurodegenerative diseases, such as Alzheimer's disease. Mild cognitive impairment is an intermediate stage between normal cognition and Alzheimer-type dementia. In vivo fibrillar amyloid-beta can be detected in PET using [11C]-labeled Pittsburgh compound B (11C-PiB). In contrast, [18F]fluoro-2-deoxy-d-glucose (18F-FDG) is a neurodegeneration biomarker used to evaluate cerebral glucose metabolism, indicating neuronal injury and synaptic dysfunction. In addition, early cerebral uptake of amyloid-PET tracers can determine regional cerebral blood flow. The present study compared early-phase 11C-PiB and 18F-FDG in older adults without cognitive impairment, amnestic mild cognitive impairment, and clinical diagnosis of probable Alzheimer's disease. Methods: We selected 90 older adults, clinically classified as healthy controls, with amnestic mild cognitive impairment, or with probable Alzheimer's disease, who underwent an 18F-FDG PET, early-phase 11C-PiB PET and magnetic resonance imaging. All participants were also classified as amyloid-positive or -negative in late-phase 11C-PiB. The data were analyzed using statistical parametric mapping. Results: We found that the probable Alzheimer's disease and amnestic mild cognitive impairment group had lower early-phase 11C-PiB uptake in limbic structures than 18F-FDG uptake. The images showed significant interactions between amyloid-beta status (negative or positive). However, early-phase 11C-PiB appears to provide different information from 18F-FDG about neurodegeneration. Conclusions: Our study suggests that early-phase 11C-PiB uptake correlates with 18F-FDG, irrespective of the particular amyloid-beta status. In addition, we observed distinct regional distribution patterns between both biomarkers, reinforcing the need for more robust studies to investigate the real clinical value of early-phase amyloid-PET imaging.

Evaluating the efficacy of hearing aids for tinnitus therapy - A Positron emission tomography study.

Brain imaging studies have revealed neural changes in chronic tinnitus patients that are not restricted to auditory brain areas; rather, the engagement of limbic system structures, attention and memory networks are has been noted. Hearing aids (HA) provide compensation for comorbid hearing loss and may decrease tinnitus-related perception and annoyance. Using resting state positron emission tomography our goal was to analyze metabolic and functional brain changes after six months of effective HA use by patients with chronic tinnitus and associated sensorineural hearing loss. 33 age and hearing loss matched participants with mild/moderate hearing loss were enrolled in this study: 19 with tinnitus, and 14 without tinnitus. Participants with tinnitus of more than 6 months with moderate/severe Tinnitus Handicap Inventory (THI) and Visual Analogue Scale (VAS) scores composed the tinnitus group. A full factorial 2X2 ANOVA was conducted for imaging analysis, with group (tinnitus and controls) and time point (pre-intervention and post-intervention) as factors. Six months after HA fitting, tinnitus scores reduced statistically and clinically. Analysis revealed increased glycolytic metabolism in the left orbitofrontal cortex, right temporal lobe and right hippocampus, and reduced glycolytic metabolism in the left cerebellum and inferior parietal lobe within the tinnitus group. The hearing loss control group showed no significant metabolic changes in the analysis. Parsing out the contribution of tinnitus independent of hearing loss, allowed us to identify areas implicated in declines in tinnitus handicap as a result of the intervention. Brain regions implicated in the present study may be part of chronic tinnitus-specific network.

Metabolic and Structural Signatures of Speech and Language Impairment in Corticobasal Syndrome: A Multimodal PET/MRI Study.

Introduction: Corticobasal syndrome (CBS) is a progressive neurological disorder related to multiple underlying pathologies, including four-repeat tauopathies, such as corticobasal degeneration and progressive supranuclear palsy, and Alzheimer's disease (AD). Speech and language are commonly impaired, encompassing a broad spectrum of deficits. We aimed to investigate CBS speech and language impairment patterns in light of a multimodal imaging approach. Materials and Methods: Thirty-one patients with probable CBS were prospectively evaluated concerning their speech-language, cognitive, and motor profiles. They underwent positron emission tomography with [18F]fluorodeoxyglucose (FDG-PET) and [11C]Pittsburgh Compound-B (PIB-PET) on a hybrid PET-MRI machine to assess their amyloid status. PIB-PET images were classified based on visual and semi-quantitative analyses. Quantitative group analyses were performed on FDG-PET data, and atrophy patterns on MRI were investigated using voxel-based morphometry (VBM). Thirty healthy participants were recruited as imaging controls. Results: Aphasia was the second most prominent cognitive impairment, presented in 67.7% of the cases, following apraxia (96.8%). We identified a wide linguistic profile, ranging from nonfluent variant-primary progressive aphasia to lexical-semantic deficits, mostly with impaired verbal fluency. PIB-PET was classified as negative (CBS-A- group) in 18/31 (58%) and positive (CBS-A+ group) in 13/31 (42%) patients. The frequency of dysarthria was significantly higher in the CBS-A- group than in the CBS-A+ group (55.6 vs. 7.7%, p = 0.008). CBS patients with dysarthria had a left-sided hypometabolism at frontal regions, with a major cluster at the left inferior frontal gyrus and premotor cortex. They showed brain atrophy mainly at the opercular frontal gyrus and putamen. There was a positive correlation between [18F]FDG uptake and semantic verbal fluency at the left inferior (p = 0.006, R 2 = 0.2326), middle (0.0054, R 2 = 0.2376), and superior temporal gyri (p = 0.0066, R 2 = 0.2276). Relative to the phonemic verbal fluency, we found a positive correlation at the left frontal opercular gyrus (p = 0.0003, R 2 = 0.3685), the inferior (p = 0.0004, R 2 = 0.3537), and the middle temporal gyri (p = 0.0001, R 2 = 0.3993). Discussion: In the spectrum of language impairment profile, dysarthria might be helpful to distinguish CBS patients not related to AD. Metabolic and structural signatures depicted from this feature provide further insights into the motor speech production network and are also helpful to differentiate CBS variants.

FDG-PET Patterns Predict Amyloid Deposition and Clinical Profile in Corticobasal Syndrome.

BACKGROUND: Corticobasal syndrome (CBS) is an atypical parkinsonian syndrome related to multiple underlying pathologies. OBJECTIVE: To investigate if individual brain [18 F]fluorodeoxyglucose-positron emission tomography (FDG-PET) patterns could distinguish CBS due to Alzheimer's disease (AD) from other pathologies based on [11 C]Pittsburgh Compound-B (PIB)-PET. METHODS: Forty-five patients with probable CBS were prospectively evaluated regarding cognitive and movement disorders profile. They underwent FDG-PET and were distributed into groups: likely related to AD (CBS FDG-AD) or likely non-AD (CBS FDG-nonAD) pathology. Thirty patients underwent PIB-PET on a hybrid PET-magnetic resonance imaging equipment to assess their amyloid status. FDG and PIB-PET images were classified individually based on visual and semi-quantitative analysis, blinded to each other. Quantitative group analyses were also performed. RESULTS: CBS FDG-AD group demonstrated worse cognitive performances, mostly concerning attention, memory, visuospatial domains, and displayed more myoclonus and hallucinations. The non-AD metabolic group presented more often limb dystonia, ocular motor dysfunction, motor perseveration, and dysarthria. All patients classified as CBS FDG-AD tested positive at PIB-PET compared to 3 of 20 in the non-AD group. The individual FDG-PET classification demonstrated 76.92% of sensitivity, 100% of specificity and positive predictive value and 88.5% of balanced accuracy to detect positive PIB-PET scans. Individuals with positive and negative PIB-PET showed hypometabolism in posterior temporoparietal areas and in thalamus and brainstem, respectively, mainly contralateral to most affected side, disclosing possible metabolic signatures of CBS variants. CONCLUSION: FDG-PET was useful to predict AD and non-AD CBS variants depicting their specific degeneration patterns, different clinical features, and brain amyloid deposition. © 2020 International Parkinson and Movement Disorder Society.

Ictal SPECT in Psychogenic Nonepileptic and Epileptic Seizures.

BACKGROUND: Psychogenic nonepileptic seizures (PNES) are a common and debilitating problem in patients with epilepsy. They can be virtually indistinguishable from epileptic seizures, demanding video-electroencaphalogram monitoring, which is costly and not widely available, for differential diagnosis. Specific functional brain correlates of PNES have not been demonstrated so far. We hypothesized that PNES and epileptic seizures have distinct brain activation patterns, assessed by functional neuroimaging during ictal events of both conditions. OBJECTIVE: Compare ictal brain activation patterns of PNES and epileptic seizures using single-photon emission computerized tomography. METHODS: We prospectively assessed brain functional activation using single-photon emission computerized tomography 99mTc-ethyl cysteinate dimer in 26 patients with PNES, confirmed by trained psychiatrists in epileptology, who had their seizures induced by provocative tests compared with 22 age- and sex-matched subjects with temporal lobe epilepsy who underwent prolonged intensive video-electroencaphalogram monitoring. RESULTS: In PNES patients compared with temporal lobe epilepsy group, we found a consistent increase in regional cerebral blood flow in the right precuneus (Brodmann area 7; P = 0.003) and right posterior cingulate cortex (Brodmann area 31; P = 0.001), as well as a decrease in regional cerebral blood flow in the right amygdala (P = 0.027). CONCLUSIONS: Activation of default mode network brain areas and temporoparietal junction may be a distinct feature of ictal PNES and could be explained by a disruption between movement prediction input and sensory outcome. Such information mismatch might be the neurobiological underpinning of dissociative episodes.

Correction to: Brain PET amyloid and neurodegeneration biomarkers in the context of the 2018 NIA-AA research framework: an individual approach exploring clinical-biomarker mismatches and sociodemographic parameters.

In the last paragraph of the subsession "Recruitment of the study population and clinical Evaluation" (Material and methods session).

Brain PET amyloid and neurodegeneration biomarkers in the context of the 2018 NIA-AA research framework: an individual approach exploring clinical-biomarker mismatches and sociodemographic parameters.

PURPOSE: [18F]FDG-PET and [11C]PIB-PET are validated as neurodegeneration and amyloid biomarkers of Alzheimer's disease (AD). We used a PET staging system based on the 2018 NIA-AA research framework to compare the proportion of amyloid positivity (A+) and hypometabolism ((N)+) in cases of mild probable AD, amnestic mild cognitive impairment (aMCI), and healthy controls, incorporating an additional classification of abnormal [18F]FDG-PET patterns and investigating the co-occurrence of such with A+, exploring [18F]FDG-PET to generate hypotheses in cases presenting with clinical-biomarker "mismatches." METHODS: Elderly individuals (N = 108) clinically classified as controls (N = 27), aMCI (N = 43) or mild probable AD (N = 38) were included. Authors assessed their A(N) profiles and classified [18F]FDG-PET neurodegenerative patterns as typical or non-typical of AD, performing re-assessments of images whenever clinical classification was in disagreement with the PET staging (clinical-biomarker "mismatches"). We also investigated associations between "mismatches" and sociodemographic and educational characteristics. RESULTS: AD presented with higher rates of A+ and (N)+. There was also a higher proportion of A+ and (N)+ individuals in the aMCI group in comparison to controls, however without statistical significance regarding the A staging. There was a significant association between amyloid positivity and AD (N)+ hypometabolic patterns typical of AD. Non-AD (N)+ hypometabolism was seen in all A- (N)+ cases in the mild probable AD and control groups and [18F]FDG-PET patterns classified such individuals as "SNAP" and one as probable frontotemporal lobar degeneration. All A- (N)- cases in the probable AD group had less than 4 years of formal education and lower socioeconomic status (SES). CONCLUSION: The PET-based staging system unveiled significant A(N) differences between AD and the other groups, whereas aMCI and controls had different (N) staging, explaining the cognitive impairment in aMCI. [18F]FDG-PET could be used beyond simple (N) staging, since it provided alternative hypotheses to cases with clinical-biomarker "mismatches." An AD hypometabolic pattern correlated with amyloid positivity. Low education and SES were related to dementia in the absence of biomarker changes.

In vivo imaging evidence of poor cognitive resilience to Alzheimer's disease pathology in subjects with very low cognitive reserve from a low-middle income environment.

INTRODUCTION: Reduced cognitive reserve (CR) due to very low educational (VLE) levels may influence high dementia rates in low-middle income environments, leading to decreased cognitive resilience (RES) to Alzheimer´s disease (AD) pathology. However, in vivo findings in VLE groups confirming this prediction are lacking. METHODS: Cognitively impaired patients (with clinically defined AD dementia or amnestic mild cognitive impairment) and cognitively unimpaired older adults (n = 126) were recruited for a positron emission tomography (PET) and magnetic resonance imaging (MRI) investigation in Brazil, including 37 VLE individuals (≤5 years of education). A CR score was generated combining educational attainment and vocabulary knowledge. RES indices to AD pathology were calculated using standardized residuals from linear regression models relating current cognitive performance (episodic memory or overall cognition) to amyloid beta (Aß) burden Pittsburgh compound-B ([11C]PiB-PET). RESULTS: Aß burden was lower in VLE relative to highly-educated subjects (controlling for age, sex, and Mini-Mental Status Exam [MMSE] scores) in the overall cognitively impaired sample, and in dementia subjects when the three clinically defined groups were evaluated separately. In bivariate regression analyses for the overall sample, the RES index based on a composite cognitive score was predicted by CR, socioeconomic status, and hippocampal volume (but not white matter hyperintensities or intracranial volume [ICV]); in the multivariate model, only CR retained significance (and similar results were obtained in the Aß-positive subsample). In the multivariate model for the overall sample using the RES index based on memory performance, CR, hippocampal volume, and ICV were significant predictors, whereas only CR retained significance in Aß-positive subjects. DISCUSSION: Lower CR consistently predicted less resilience to AD pathology in older adults from a low-middle income environment.

Insular and anterior cingulate cortex deep stimulation for central neuropathic pain: Disassembling the percept of pain.

OBJECTIVE: To compare the analgesic effects of stimulation of the anterior cingulate cortex (ACC) or the posterior superior insula (PSI) against sham deep (d) repetitive (r) transcranial magnetic stimulation (TMS) in patients with central neuropathic pain (CNP) after stroke or spinal cord injury in a randomized, double-blinded, sham-controlled, 3-arm parallel study. METHODS: Participants were randomly allocated into the active PSI-rTMS, ACC-rTMS, sham-PSI-rTMS, or sham-ACC-rTMS arms. Stimulations were performed for 12 weeks, and a comprehensive clinical and pain assessment, psychophysics, and cortical excitability measurements were performed at baseline and during treatment. The main outcome of the study was pain intensity (numeric rating scale [NRS]) after the last stimulation session. RESULTS: Ninety-eight patients (age 55.02 ± 12.13 years) completed the study. NRS score was not significantly different between groups at the end of the study. Active rTMS treatments had no significant effects on pain interference with daily activities, pain dimensions, neuropathic pain symptoms, mood, medication use, cortical excitability measurements, or quality of life. Heat pain threshold was significantly increased after treatment in the PSI-dTMS group from baseline (1.58, 95% confidence interval [CI] 0.09-3.06]) compared to sham-dTMS (-1.02, 95% CI -2.10 to 0.04, p = 0.014), and ACC-dTMS caused a significant decrease in anxiety scores (-2.96, 95% CI -4.1 to -1.7]) compared to sham-dTMS (-0.78, 95% CI -1.9 to 0.3; p = 0.018). CONCLUSIONS: ACC- and PSI-dTMS were not different from sham-dTMS for pain relief in CNP despite a significant antinociceptive effect after insular stimulation and anxiolytic effects of ACC-dTMS. These results showed that the different dimensions of pain can be modulated in humans noninvasively by directly stimulating deeper SNC cortical structures without necessarily affecting clinical pain per se. CLINICALTRIALSGOV IDENTIFIER: NCT01932905.

Pulmonary inhalation-perfusion scintigraphy in the evaluation of bronchoscopic treatment of bronchopleural fistula.

OBJECTIVE: To evaluate the use of pulmonary inhalation-perfusion scintigraphy as an alternative method of investigation and follow-up in patients with bronchopleural fistula (BPF). MATERIALS AND METHODS: Nine patients with BPFs were treated through the off-label use of a transcatheter atrial septal defect occluder, placed endoscopically, and were followed with pulmonary inhalation-perfusion scintigraphy, involving inhalation, via a nebulizer, of 900-1300 MBq (25-35 mCi) of technetium-99m-labeled diethylenetriaminepentaacetic acid and single-photon emission computed tomography with a dual-head gamma camera. RESULTS: In two cases, there was a residual air leak that was not identified by bronchoscopy or the methylene blue test but was detected only by pulmonary inhalation-perfusion scintigraphy. Those results correlated with the evolution of the patients, both of whom showed late signs of air leak, which confirmed the scintigraphy findings. In the patients with complete resolution of symptoms and fistula closure seen on bronchoscopy, the scintigraphy was completely negative. In cases of failure to close the BPF, the scintigraphy confirmed the persistence of the air leak. In two patients, scintigraphy was the only method to show residual BPF, the fistula no longer being seen on bronchoscopy. CONCLUSION: We found pulmonary inhalation-perfusion scintigraphy to be a useful tool for identifying a residual BPF, as well as being an alternative method of investigating BPFs and of monitoring the affected patients.

Pulmonary inhalation-perfusion scintigraphy in the evaluation of bronchoscopic treatment of bronchopleural fistula / Cintilografia pulmonar inalatória na avaliação do tratamento broncoscópico de fístula broncopleural

Abstract Objective: To evaluate the use of pulmonary inhalation-perfusion scintigraphy as an alternative method of investigation and follow-up in patients with bronchopleural fistula (BPF). Materials and Methods: Nine patients with BPFs were treated through the off-label use of a transcatheter atrial septal defect occluder, placed endoscopically, and were followed with pulmonary inhalation-perfusion scintigraphy, involving inhalation, via a nebulizer, of 900-1300 MBq (25-35 mCi) of technetium-99m-labeled diethylenetriaminepentaacetic acid and single-photon emission computed tomography with a dual-head gamma camera. Results: In two cases, there was a residual air leak that was not identified by bronchoscopy or the methylene blue test but was detected only by pulmonary inhalation-perfusion scintigraphy. Those results correlated with the evolution of the patients, both of whom showed late signs of air leak, which confirmed the scintigraphy findings. In the patients with complete resolution of symptoms and fistula closure seen on bronchoscopy, the scintigraphy was completely negative. In cases of failure to close the BPF, the scintigraphy confirmed the persistence of the air leak. In two patients, scintigraphy was the only method to show residual BPF, the fistula no longer being seen on bronchoscopy. Conclusion: We found pulmonary inhalation-perfusion scintigraphy to be a useful tool for identifying a residual BPF, as well as being an alternative method of investigating BPFs and of monitoring the affected patients.

Resumo Objetivo: Avaliar a cintilografia por inalação-perfusão pulmonar como método alternativo de investigação e acompanhamento em pacientes com fístula broncopleural (FBP). Materiais e Métodos: Nove pacientes com FBPs foram tratados de forma endoscópica com o uso off label de um oclusor transcateter de defeito do septo interatrial e foram seguidos com cintilografia de inalação-perfusão pulmonar usando tomografia computadorizada por emissão de fóton único com câmera de cintilação de duas cabeças e inalação com 900-1300 MBq (25-35 mCi) de ácido dietilenotriaminopentacético marcado com tecnécio-99m, inserido num nebulizador. Resultados: Broncoscopia e teste de azul de metileno não foram capazes de detectar dois casos de vazamento residual, detectados apenas por cintilografia por inalação-perfusão pulmonar. Esses resultados foram correlacionados com a evolução desses pacientes que tardiamente apresentaram sinais de vazamento de ar confirmando os achados da cintilografia. Pacientes com resolução completa dos sintomas e com aspecto broncoscópico do fechamento da fístula apresentaram cintilografia negativa completa. Em casos de falha no fechamento da FBP, a cintilografia por inalação-perfusão confirmou a persistência da fuga de ar. Em dois pacientes, a cintilografia foi o único método a mostrar FBP residual, apesar da ausência da fístula por avaliação broncoscópica. Conclusão: Neste estudo, a cintilografia de inalação-perfusão pulmonar mostrou ser um instrumento útil para identificar FBP residual e como método alternativo de investigação e seguimento de pacientes com FBPs.

Methods for quantification of cerebral glycolytic metabolism using 2-deoxy-2-[18 F]fluoroglucose in small animals

Abstract Introduction The use of the same imaging and quantification techniques in small animals and clinical studies presents the opportunity for direct translational research in drug discovery and development, in neuropharmacological basis of neurological and psychiatric diseases, and in optimization of drug therapy. Thus, positron emission tomography (PET) studies in rodents can bridge the gap between pre-clinical and clinical research. The aim should be to find a method with capability to measure, without compromising accuracy, glucose distribution in the structures of the brain, which can also be used in pathological situations and with applicability for other substances than glucose analogue. Methods This is a systematic review of several assessment techniques available, including visual and quantitative methods that enable the investigation of the transport mechanisms and enzymes involved in glucose metabolism in the brain. In addition to the ex vivo methods, PET with glucose analogues allows in vivo analyses using qualitative, semiquantitative and quantitative methods. Results These techniques provide different results, and the applicability of a specific method is related to the purpose of the study and the multiple factors that may interfere in the process. Conclusion This review provides a solid background of tools and quantification methods for medical physicists and other professionals interested in cerebral glycolytic metabolism quantification in experimental animals. It also addresses the main factors related to animals, equipment and techniques that are used, as well as how these factors should be understood to better interpret the results obtained from experiments.

Intracranial germinoma causing cerebral haemiatrophy and hypopituitarism.

A young woman presented with primary amenorrhoea, progressive haemiparesis, visual disturbance, dementia and focal motor seizures. Investigations showed hypopituitarism, unilateral cerebral atrophy and inflamed cerebrospinal fluid. A trans-sphenoidal biopsy gave a unifying diagnosis of a pituitary germinoma.

Selecting the most relevant brain regions to discriminate Alzheimer's disease patients from healthy controls using multiple kernel learning: A comparison across functional and structural imaging modalities and atlases.

BACKGROUND: Machine learning techniques such as support vector machine (SVM) have been applied recently in order to accurately classify individuals with neuropsychiatric disorders such as Alzheimer's disease (AD) based on neuroimaging data. However, the multivariate nature of the SVM approach often precludes the identification of the brain regions that contribute most to classification accuracy. Multiple kernel learning (MKL) is a sparse machine learning method that allows the identification of the most relevant sources for the classification. By parcelating the brain into regions of interest (ROI) it is possible to use each ROI as a source to MKL (ROI-MKL). METHODS: We applied MKL to multimodal neuroimaging data in order to: 1) compare the diagnostic performance of ROI-MKL and whole-brain SVM in discriminating patients with AD from demographically matched healthy controls and 2) identify the most relevant brain regions to the classification. We used two atlases (AAL and Brodmann's) to parcelate the brain into ROIs and applied ROI-MKL to structural (T1) MRI, 18F-FDG-PET and regional cerebral blood flow SPECT (rCBF-SPECT) data acquired from the same subjects (20 patients with early AD and 18 controls). In ROI-MKL, each ROI received a weight (ROI-weight) that indicated the region's relevance to the classification. For each ROI, we also calculated whether there was a predominance of voxels indicating decreased or increased regional activity (for 18F-FDG-PET and rCBF-SPECT) or volume (for T1-MRI) in AD patients. RESULTS: Compared to whole-brain SVM, the ROI-MKL approach resulted in better accuracies (with either atlas) for classification using 18F-FDG-PET (92.5% accuracy for ROI-MKL versus 84% for whole-brain), but not when using rCBF-SPECT or T1-MRI. Although several cortical and subcortical regions contributed to discrimination, high ROI-weights and predominance of hypometabolism and atrophy were identified specially in medial parietal and temporo-limbic cortical regions. Also, the weight of discrimination due to a pattern of increased voxel-weight values in AD individuals was surprisingly high (ranging from approximately 20% to 40% depending on the imaging modality), located mainly in primary sensorimotor and visual cortices and subcortical nuclei. CONCLUSION: The MKL-ROI approach highlights the high discriminative weight of a subset of brain regions of known relevance to AD, the selection of which contributes to increased classification accuracy when applied to 18F-FDG-PET data. Moreover, the MKL-ROI approach demonstrates that brain regions typically spared in mild stages of AD also contribute substantially in the individual discrimination of AD patients from controls.

Which factors are associated with global cognitive impairment in Wilson's disease? / Quais fatores estão associados ao comprometimento cognitivo global na doença de Wilson?

ABSTRACT Background: Patients with Wilson's disease (WD) present cognitive impairment, especially in executive functions. Which other factors might be associated with global cognitive decline in these patients remains unclear. Objective: To assess which factors are associated with worse performance on a global cognitive test in patients with WD. Methods: Twenty patients with WD underwent cognitive assessment with the following tests: the Mini-Mental State Examination (MMSE), Dementia Rating Scale (DRS), verbal fluency test, brief cognitive battery, clock drawing test, Frontal Assessment Battery, Stroop test, Wisconsin card sorting test, Hopper test, cubes (WAIS) and the Pfeffer questionnaire. MRI changes were quantified. Patients with poor performance on the DRS were compared to patients with normal performance. Results: Nine patients had a poor performance on the DRS. This group had lower educational level (9.11±3.58 × 12.82±3.06) and a greater number of changes on MRI (9.44±2.74 × 6.27±2.45). The presence of hyperintensity in the globus pallidus on MRI was more frequent in this group (66.6% vs 9.0%), with OR=5.38 (95% CI 0.85-33.86). Conclusion: Global cognitive impairment was prevalent in this sample of patients with WD and was associated with low educational level, number of changes on MRI and MRI hyperintensity in the globus pallidus.

RESUMO Embasamento: Pacientes com doença de Wilson (DW) apresentam comprometimento cognitivo, principalmente de funções executivas. Existem dúvidas sobre quais outros fatores poderiam estar associados ao declínio cognitivo global nesses pacientes. Objetivo: Avaliar quais fatores estão associados ao pior desempenho em teste cognitivo global em pacientes com DW. Métodos: Vinte pacientes com DW em tratamento regular foram submetidos à avaliação cognitiva com os seguintes testes: Mini-Exame do Estado Mental, escala de demência de Mattis (DRS), fluência verbal, bateria cognitiva breve, desenho do relógio, bacteria de avaliação frontal, Stroop, teste de seleção de cartões de Wisconsin, Hopper, Cubos e ao questionário de Pfeffer. As alterações em RM foram quantificadas. Pacientes com desempenho alterado na DRS foram comparados aos pacientes com desempenho normal. Resultados: Nove pacientes apresentavam desempenho alterado na DRS. Eles apresentavam menor nivel educacional (9,11±3,58 × 12,82±3,06 anos, respectivamente) e maior quantidade de alterações na RM (9,44±2,74 × 6,27±2,45). A presença de hipersinal no globo pálido na RM foi mais frequente nesse grupo (66,6% × 9,0%), com OR=5,38 (IC 95% 0,85-33,86). Conclusão: Alterações cognitivas globais foram frequentes nesta amostra de pacientes com DW e se associaram à baixa escolaridade, quantidade de alterações em RM e a hipersinal no globo pálido à RM.

Receiver operating characteristic (ROC) curve for classification of (18)F-NaF uptake on PET/CT.

OBJECTIVE: To assess the cutoff values established by ROC curves to classify (18)F-NaF uptake as normal or malignant. MATERIALS AND METHODS: PET/CT images were acquired 1 hour after administration of 185 MBq of (18)F-NaF. Volumes of interest (VOIs) were drawn on three regions of the skeleton as follows: proximal right humerus diaphysis (HD), proximal right femoral diaphysis (FD) and first vertebral body (VB1), in a total of 254 patients, totalling 762 VOIs. The uptake in the VOIs was classified as normal or malignant on the basis of the radiopharmaceutical distribution pattern and of the CT images. A total of 675 volumes were classified as normal and 52 were classified as malignant. Thirty-five VOIs classified as indeterminate or nonmalignant lesions were excluded from analysis. The standardized uptake value (SUV) measured on the VOIs were plotted on an ROC curve for each one of the three regions. The area under the ROC (AUC) as well as the best cutoff SUVs to classify the VOIs were calculated. The best cutoff values were established as the ones with higher result of the sum of sensitivity and specificity. RESULTS: The AUCs were 0.933, 0.889 and 0.975 for UD, FD and VB1, respectively. The best SUV cutoffs were 9.0 (sensitivity: 73%; specificity: 99%), 8.4 (sensitivity: 79%; specificity: 94%) and 21.0 (sensitivity: 93%; specificity: 95%) for UD, FD and VB1, respectively. CONCLUSION: The best cutoff value varies according to bone region of analysis and it is not possible to establish one value for the whole body.

Receiver operating characteristic (ROC) curve for classification of18F-NaF uptake on PET/CT / Curva de característica de operação do receptor (ROC) para classificação da captação de 18F-NaF em PET/CT

Abstract Objective: To assess the cutoff values established by ROC curves to classify18F-NaF uptake as normal or malignant. Materials and Methods: PET/CT images were acquired 1 hour after administration of 185 MBq of18F-NaF. Volumes of interest (VOIs) were drawn on three regions of the skeleton as follows: proximal right humerus diaphysis (HD), proximal right femoral diaphysis (FD) and first vertebral body (VB1), in a total of 254 patients, totalling 762 VOIs. The uptake in the VOIs was classified as normal or malignant on the basis of the radiopharmaceutical distribution pattern and of the CT images. A total of 675 volumes were classified as normal and 52 were classified as malignant. Thirty-five VOIs classified as indeterminate or nonmalignant lesions were excluded from analysis. The standardized uptake value (SUV) measured on the VOIs were plotted on an ROC curve for each one of the three regions. The area under the ROC (AUC) as well as the best cutoff SUVs to classify the VOIs were calculated. The best cutoff values were established as the ones with higher result of the sum of sensitivity and specificity. Results: The AUCs were 0.933, 0.889 and 0.975 for UD, FD and VB1, respectively. The best SUV cutoffs were 9.0 (sensitivity: 73%; specificity: 99%), 8.4 (sensitivity: 79%; specificity: 94%) and 21.0 (sensitivity: 93%; specificity: 95%) for UD, FD and VB1, respectively. Conclusion: The best cutoff value varies according to bone region of analysis and it is not possible to establish one value for the whole body.

Resumo Objetivo: Acessar valores de corte estabelecidos pela curva ROC para classificar a captação de 18F-NaF como normal ou maligna. Materiais e Métodos: Imagens de PET/CT foram realizadas 1 hora após a administração de 185 MBq de18F-NaF e volumes de interesse (VOIs) foram desenhados em três regiões do esqueleto: diáfise umeral proximal direita (UD), diáfise femoral proximal direita (FD) e corpo da primeira vértebra lombar (VB1), em 254 pacientes, totalizando 762 VOIs. A captação nos VOIs foi classificada como normal ou maligna baseada no padrão de distribuição do radiofármaco e nas imagens de CT. Um total de 675 volumes foi classificado como normais e 52 como malignos. Trinta e cinco VOIs classificados como indeterminados ou lesões não malignas foram excluídos da análise. Os valores de captação (SUVs) medidos nos VOIs foram plotados em uma curva ROC para cada uma das três regiões. Foi calculada a área sob a curva (AUC), bem como os valores de SUV mais adequados para a classificação dos VOIs (maior resultado da soma da sensibilidade e especificidade). Resultados: As AUCs foram 0,933, 0,889 e 0,975 para UD, FD e VB1, respectivamente. Os valores de corte mais adequados de SUV foram 9,0 (sensibilidade: 73%; especificidade: 99%), 8,4 (sensibilidade: 79%; especificidade: 94%) e 21,0 (sensibilidade: 93%; especificidade: 95%)para UD, FD e VB1, respectivamente. Conclusão: O valor de corte de SUV mais adequado varia de acordo com a região óssea em análise e não é possível estabelecer um valor adequado para todo o esqueleto.