New avenues in PET imaging of multiple sclerosis

Multiple sclerose is een neurodegeneratieve aandoening waarbij ontstekingen en het verlies van de myelineschede rondom de zenuwvezels leidt tot ernstige neurologische verschijnselen. Positron Emissie Tomografie (PET) is een beeldvormende techniek waarmee het ontstaan en de voortgang van ziekteprocessen in het centraal zenuwstelsel zichtbaar gemaakt kan worden. Bij PET wordt een kortlevende radioactieve stof, een “tracer”, intraveneus geïnjecteerd, waarna een 3D afbeelding van ons lichaam kan worden verkregen. Uit de PET scan kan specifieke moleculair informatie over (afwijkingen in) fysiologische en biochemische processen in de patiënt worden verkregen. Het doel van het onderzoek beschreven in dit proefschrift is het evalueren van de mogelijkheid om PET te gebruiken voor het vaststellen van myelineverlies en het volgen van ontstekingsprocessen in het zenuwstelsel van proefdieren waarin MS is opgewekt. Uit ons PET onderzoek met een specifieke tracer voor ontstekingen in de hersenen, [11C]PK11195, bleek dat de activering van ontstekingscellen in de hersenen uitstekend kan worden gevolgd. PET bleek ook een gevoelige methode te zijn om het effect van ontstekingsremmende middelen te meten. Daarnaast hebben wij nieuwe PET tracers voor het afbeelden myeline geëvalueerd in diermodellen voor MS en aangetoond dat met name de tracer [11C]MeDAS geschikt is om afbraak en herstel van myeline in de hersenen en het ruggenmerg zichtbaar te maken. Echter, deze tracer in de kliniek kan worden gebruikt, zal eerst de veiligheid en specificiteit verder getest moeten worden. Ons onderzoek heeft laten zien dat PET nieuwe mogelijkheden biedt om de ziekteprocessen in het zenuwstelsel van MS patiënten in beeld te brengen.

Evaluation of costs for quality control of [99mTc]technetium radiopharmaceuticals in Brazilian nuclear medicine centers

OBJETIVO: Estabelecer os custos dos controles de qualidade para os radiofármacos marcados com [99mTc]tecnécio nos serviços de medicina nuclear do Brasil, em atenção às resoluções RDC nº 38/2008 e RDC nº 63/2009 editadas pela Agência Nacional de Vigilância Sanitária. MATERIAIS E MÉTODOS: Foram apurados preços de materiais de consumo, equipamentos e de mão-de-obra para a realização dos controles de qualidade. Os valores foram convertidos para unidades de volume, tempo e outras unidades cabíveis para a determinação do preço unitário. RESULTADOS: O investimento para aquisição de materiais de consumo e equipamentos foi estimado ser de R$35.500,00. O custo final para o controle de cada kit variou entre R$ 6,44 e R$7,80, dependendo do produto a ser analisado e do profissional selecionado para execução do procedimento. Esses valores podem representar de 0,5$ 35,500.00. The final unit cost for quality control of a [99mTc]technetium radiopharmaceutical kit ranged from R$6.44 to R$ 7.80 per kit, depending on the product under analysis, on the methodology applied and on the qualification of the professional involved in the process. Such values may correspond to 0.5% to 10% of the amount received by the institution per diagnostic procedure. In practice the effective cost might be lower, considering that a single labeled kit can be fractionated into several doses. CONCLUSION: Considering the gains in quality and patients' safety, the authors conclude that costs for implementing a quality control program for radiopharmaceuticals can be absorbed in the financial planning of nuclear medicine centers

Tratamentos Alternativos para Onicomicose: Ondas de Alta Frequência e Laser

Onychomycosis is a type of mycosis that affect nails and it is difficult to be diagnosed and to be treated. The objective of this study was to evaluate, in patients of both sexes, treated at a podiatry clinic in the city of Araraquara, the effectiveness of two treatments for dermatophytic onychomycosis using the application of high frequency waves and photodynamic therapy (PDT). High frequency waves and PDT are alternative therapies that are already used in aesthetic clinics and may help in the treatment of onychomycosis. The research was developed with five volunteer patients, with onychomycosis on the feet. In patient 1, only high frequency waves were applied for 15 months; in patient 2, we have used the application of high frequency for 8 months and laser, for 7 months; and with the other 3 patients, we have used only the laser treatment for 6 months, 4 months and 6 months, respectively. Once a month the nails were cleaned and material for mycological examination (direct exam and culture) was collected. The five patients studied presented positive direct mycological examination during the treatment, but with a gradual decrease in the fungal structures. In patients who used only the highfrequency waves, despite good results, it took a long time to observe the clinical improvement of the nails. In the patients who used the two treatments, there was a faster improvement of the nails when they started using the laser. In the patients treated with laser, there was a noticeable improvement of the nails soon after the second application. The laser treatment was more efficient and advantageous because the applications were done each two weeks and the results were seen more quickly.As onicomicoses são micoses que acometem as unhas e são infecções difíceis de diagnosticar e tratar. O objetivo deste trabalho foi avaliar em pacientes de ambos os sexos, atendidos em uma clínica de podologia na cidade de Araraquara, a eficácia de dois tratamentos para onicomicoses dermatofíticas, utilizando a aplicação de ondas de alta frequência e a terapia fotodinâmica (laser). Ondas de alta frequência e terapia fotodinâmica são terapias alternativas que já são usadas em clínicas de estética e podem auxiliar no tratamento de onicomicose. A pesquisa foi realizada com cinco pacientes voluntários, portadores de onicomicose nos pés. No paciente 1, foi aplicada apenas as de alta frequência, durante 15 meses; no paciente 2 foi utilizada a aplicação de alta frequência por 8 meses e de laser por 7 meses; e, com os outros 3 pacientes, foi utilizado apenas o tratamento com o laser, durante 6 meses, 4 meses e 6 meses, respectivamente. A cada mês foi realizada a limpeza das unhas e retirado material para análise micológica. Os cinco pacientes analisados apresentaram exame micológico direto positivo durante todo o tratamento, mas com uma diminuição gradativa das estruturas fúngicas. Nos pacientes que utilizaram apenas as ondas de alta frequência, apesar dos bons resultados, demorou muito tempo para se observar a melhora clínica das unhas. Nos pacientes em que foram utilizados os dois tratamentos, houve melhora das unhas mais rapidamente quando iniciado o uso do laser. Já nos pacientes tratados apenas com o laser, houve uma melhora visível das unhas logo após a segunda aplicação. O tratamento com o laser foi mais eficiente e vantajoso, pois as aplicações foram quinzenais e os resultados visualizados mais rapidamente

Environmental Tobacco Smoke During the Early Postnatal Period of Mice Interferes With Brain 18 F-FDG Uptake From Infancy to Early Adulthood – A Longitudinal Study

Exposure to environmental tobacco smoke (ETS) is associated with high morbidity and mortality, mainly in childhood. Our aim was to evaluate the effects of postnatal ETS exposure in the brain 2-deoxy-2-[18F]-fluoro-D-glucose (18F-FDG) uptake of mice by positron emission tomography (PET) neuroimaging in a longitudinal study. C57BL/6J mice were exposed to ETS that was generated from 3R4F cigarettes from postnatal day 3 (P3) to P14. PET analyses were performed in male and female mice during infancy (P15), adolescence (P35), and adulthood (P65). We observed that ETS exposure decreased 18F-FDG uptake in the whole brain, both left and right hemispheres, and frontal cortex in both male and female infant mice, while female infant mice exposed to ETS showed decreased 18F-FDG uptake in the cerebellum. In addition, all mice showed reduced 18F-FDG uptake in infancy, compared to adulthood in all analyzed VOIs. In adulthood, ETS exposure during the early postnatal period decreased brain 18F-FDG uptake in adult male mice in the cortex, striatum, hippocampus, cingulate cortex, and thalamus when compared to control group. ETS induced an increase in 18F-FDG uptake in adult female mice when compared to control group in the brainstem and cingulate cortex. Moreover, male ETS-exposed animals showed decreased 18F-FDG uptake when compared to female ETS-exposed in the whole brain, brainstem, cortex, left amygdala, striatum, hippocampus, cingulate cortex, basal forebrain and septum, thalamus, hypothalamus, and midbrain. The present study shows that several brain regions are vulnerable to ETS exposure during the early postnatal period and these effects on 18F-FDG uptake are observed even a long time after the last exposure. This study corroborates our previous findings, strengthening the idea that exposure to tobacco smoke in a critical period interferes with brain development of mice from late infancy to early adulthood

[C-11]PIB PET imaging can detect white and grey matter demyelination in a non-human primate model of progressive multiple sclerosis

Background: Multiple sclerosis (MS) is a demyelinating and inflammatory disease of the central nervous system. Its diagnosis is clinical, often confirmed by magnetic resonance imaging. This image modality, however, is not ideal for discrimination of demyelination in grey and white matter regions from inflammatory lesions. Positron Emission Tomography (PET), using specific radiopharmaceuticals, can be a tool to differentiate between these processes. The radiopharmaceutical [C-11]PIB is widely used for detection of beta-amyloid plaques, but has also been suggested for the analysis of myelin content due to its consistent uptake in white matter. The aim of this study was to evaluate [C-11]PIB PET imaging as a tool for detecting demyelinated regions in white and grey matter of non-human primate model of progressive MS. Methods: Experimental autoimmune encephalomyelitis (EAE) was induced in marmosets by injection of re-combinant human myelin oligodendrocyte glycoprotein (rhMOG) emulsified in either Incomplete Freund's Adjuvant (IFA) or Complete Freund's Adjuvant (CFA). [C-11]PIB PET images were acquired prior to immunization (baseline) and after symptoms were present (end of experiment). Brain tissue was isolated for histochemical analysis. Results: All rhMOG/IFA-treated and rhMOG/CFA-treated animals showed clinical signs of EAE. The rhMOG/CFA group presented a significant [C-11]PIB uptake reduction only in the left motor cortex (9%, P = 0.011). For the rhMOG/IFA group, significant decrease in [C-11]PIB uptake was observed in the whole brain (15%, P = 0.015), in the right hemisphere of body of corpus callosum (34%, P = 0.02), splenium of corpus callosum (38%, P = 0.004), hippocampus (19%, P = 0.036), optic tract (13%, P = 0.025), thalamus (14%, P = 0.041), Globus pallidus (23%, P = 0.017), head of caudate nucleus (25%, P = 0.045), tail of caudate nucleus (29%, P = 0.003), putamen (28%, P = 0.047) and left hemisphere of body of corpus callosum (14%, P = 0.037) and head of caudate nucleus (23%, P = 0.023). [C-11]PIB uptake significantly correlated with luxol fast blue histology (myelin marker), both in the rhMOG/IFA (r(2) = 0.32, P <0.0001) and the rhMOG/CFA group (r(2) = 0.46, P <0.0001). Conclusion: [C-11]PIB PET imaging is an efficient tool for detecting demyelination in grey and white matter, in a non-human primate model of progressive MS

Perfil neuropsiquiátrico de crianças, adolescentes e jovens adultos com complexo de esclerose tuberosa

Aim: to assess neuropsychiatric disorders and factors related to the intellectual level of patients with Tuberous sclerosis complex (TSC).Method: a cross-sectional study with 20 patients diagnosed with TSC, recruited in a pediatric neurology center, was conducted. Participants were assessed by semi-structured interviews, medical chart information, the Wechsler Intelligence Scale, the Childhood Autism Rating Scale and the Child Behavior Checklist /Adult Self Report. A descriptive analysis of data was performed for each variable. The Comparison between groups with and without intellectual disability was performed using Mann-Whitney U test and Fisher test. Results: Ninety-five percent of the participants presented epilepsy, 45% intellectual deficit and 25% autistic disorder. The sample also presented clinical manifestations of conduct disorder, anxiety disorder and avoidant personality. There was a significant relationship between intellectual deficit and the following variables: number of medications used for epilepsy (p=0.002), use of benzodiazepine in the treatment of epilepsy (p=0.005) and autism (p=0.008).Conclusion: The sample presented a high prevalence of epilepsy, cognitive deficit and psychiatric disorders, as demonstrated by other studies in similar population. Intellectual deficit was associated with a higher number of drugs used to treat epilepsy and autism.Objetivo: avaliar alterações neuropsiquiátricas e avaliar fatores associados a déficit intelectual em pacientes com Complexo de Esclerose Tuberosa (CET).Métodos: estudo transversal com 20 pacientes com diagnóstico de CET em um centro de neurologia pediátrica, avaliados por entrevista, prontuário, Escalas Wechsler de Inteligência, Escala Childhood Autism Rating Scale e Questionário Child Behavior Checklist /Adult Self Report. Foi realizada análise descritiva para caracterização das variáveis e os testes Mann-Whitney U e Teste de Fisher para comparação de grupo sem e com déficit intelectual.Resultados: Noventa e cinco por cento dos participantes apresentou epilepsia, 45% déficit intelectual e 25% autismo. Encontraram-se ainda manifestações clínicas de problemas de conduta, ansiedade e personalidade esquiva. Houve relação significativa entre déficit intelectual e as seguintes variáveis: número de medicamentos para controle da epilepsia (p=0,002), uso de benzodiazepínicos associados a anticonvulsivantes no tratamento da epilepsia (p=0,005) e autismo (p=0,008).Conclusões: Foi encontrada alta prevalência de epilepsia, déficit cognitivo e manifestações psiquiátricas, condizente com descrições da literatura atual. O déficit intelectual mostrou-se associado a um maior número de fármacos no controle de epilepsia e ao autismo

The effect of lesion filling on brain network analysis in multiple sclerosis using structural magnetic resonance imaging

BACKGROUND: Graph theoretical network analysis with structural magnetic resonance imaging (MRI) of multiple sclerosis (MS) patients can be used to assess subtle changes in brain networks. However, the presence of multiple focal brain lesions might impair the accuracy of automatic tissue segmentation methods, and hamper the performance of graph theoretical network analysis. Applying "lesion filling" by substituting the voxel intensities of a lesion with the voxel intensities of nearby voxels, thus creating an image devoid of lesions, might improve segmentation and graph theoretical network analysis. This study aims to determine if brain networks are different between MS subtypes and healthy controls (HC) and if the assessment of these differences is affected by lesion filling. METHODS: The study included 49 MS patients and 19 HC that underwent a T1w, and T2w-FLAIR MRI scan. Graph theoretical network analysis was performed from grey matter fractions extracted from the original T1w-images and T1w-images after lesion filling. RESULTS: Artefacts in lesion-filled T1w images correlated positively with total lesion volume (r = 0.84, p < 0.001) and had a major impact on grey matter segmentation accuracy. Differences in sensitivity for network alterations were observed between original T1w data and after application of lesion filling: graph theoretical network analysis obtained from lesion-filled T1w images produced more differences in network organization in MS patients. CONCLUSION: Lesion filling might reduce variability across subjects resulting in an increased detection rate of network alterations in MS, but also induces significant artefacts, and therefore should be applied cautiously especially in individuals with higher lesions loads

Deficits in short-term memory binding are detectable in individuals with brain amyloid deposition in the absence of overt neurodegeneration in the Alzheimer's disease continuum

The short-term memory binding (STMB) test involves the ability to hold in memory the integration between surface features, such as shapes and colours. The STMB test has been used to detect Alzheimer’s disease (AD) at different stages, from preclinical to dementia, showing promising results. The objective of the present study was to verify whether the STMB test could differentiate patients with distinct biomarker profiles in the AD continuum. The sample comprised 18 cognitively unimpaired (CU) participants, 30 mild cognitive impairment (MCI) and 23 AD patients. All participants underwent positron emission tomography (PET) with Pittsburgh compound-B labelled with carbon-11 ([11C]PIB) assessing amyloid beta (Aβ) aggregation (A) and 18fluorine-fluorodeoxyglucose ([18F]FDG)-PET assessing neurodegeneration (N) (A-N- [n = 35]); A+N- [n = 11]; A+N+ [n = 19]). Participants who were negative and positive for amyloid deposition were compared in the absence (A-N- vs. A+N-) of neurodegeneration. When compared with the RAVLT and SKT memory tests, the STMB was the only cognitive task that differentiated these groups, predicting the group outcome in logistic regression analyses. The STMB test showed to be sensitive to the signs of AD pathology and may represent a cognitive marker within the AD continuum