Validation of automated image co-registration integrated into in-house software for voxel-based internal dosimetry on single-photon emission computed tomography images / Validação do corregistro automático de imagem integrado a software de análise de dosimetria interna baseada em voxel para tomografia computadorizada de emissão de fóton único

Abstract Objective: To develop an automated co-registration system and test its performance, with and without a fiducial marker, on single-photon emission computed tomography (SPECT) images. Materials and Methods: Three SPECT/CT scans were acquired for each rotation of a Jaszczak phantom (to 0°, 5°, and 10° in relation to the bed axis), with and without a fiducial marker. Two rigid co-registration software packages-SPM12 and NMDose-coreg-were employed, and the percent root mean square error (%RMSE) was calculated in order to assess the quality of the co-registrations. Uniformity, contrast, and resolution were measured before and after co-registration. The NMDose-coreg software was employed to calculate the renal doses in 12 patients treated with 177Lu-DOTATATE, and we compared those with the values obtained with the Organ Level INternal Dose Assessment for EXponential Modeling (OLINDA/EXM) software. Results: The use of a fiducial marker had no significant effect on the quality of co-registration on SPECT images, as measured by %RMSE (p = 0.40). After co-registration, uniformity, contrast, and resolution did not differ between the images acquired with fiducial markers and those acquired without. Preliminary clinical application showed mean total processing times of 9 ± 3 min/patient for NMDose-coreg and 64 ± 10 min/patient for OLINDA/EXM, with a strong correlation between the two, despite the lower renal doses obtained with NMDose-coreg. Conclusion: The use of NMDose-coreg allows fast co-registration of SPECT images, with no loss of uniformity, contrast, or resolution. The use of a fiducial marker does not appear to increase the accuracy of co-registration on phantoms.

Resumo Objetivo: Desenvolver corregistro automático e testar seu desempenho com ou sem marcador fiducial em imagens de tomografia computadorizada de emissão de fóton único (SPECT). Materiais e Métodos: Três SPECT/CTs foram adquiridas para cada rotação de um simulador de Jaszczak em relação ao eixo da maca (0°, 5° e 10°), com e sem fiducial. Dois métodos de corregistro inelástico foram aplicados - SPM12 e NMDose-coreg -, e a porcentagem do erro quadrático médio (%RMSE) foi usada para analisar a qualidade do corregistro. Uniformidade, contraste e resolução foram medidos antes e após o corregistro. NMDose com corregistro automático foi usado para calcular a dose renal de 12 pacientes tratados com 177Lu-DOTATATE e comparado com OLINDA/EXM. Resultados: A marcação fiducial não modificou a qualidade do corregistro das imagens SPECT, medida pela %RMSE (p = 0,40). Não houve impacto na uniformidade, contraste e resolução após o corregistro de imagens adquiridas com ou sem fiduciais. Aplicação clínica preliminar mostrou tempo total de processamento de 9 ± 3 min/paciente para NMDose e 64 ± 10 min/paciente para OLINDA/EXM, com alta correlação entre ambos, apesar de menor dose renal em NMDose. Conclusão: NMDose-coreg permite o corregistro rápido de imagens SPECT, sem perda de uniformidade, contraste ou resolução. O uso da marcação fiducial não aumentou a precisão do corregistro em fantomas.

Brain glucose metabolism and gray matter volume in retired professional soccer players: a cross-sectional [18F]FDG-PET/MRI study / Metabolismo glicolítico cerebral e volume de substância cinzenta em jogadores de futebol profissionais aposentados: um estudo transversal de [18F]FDG-PET/RM

Abstract Background Professional soccer athletes are exposed to repetitive head impacts and are at risk of developing chronic traumatic encephalopathy. Objective To evaluate regional brain glucose metabolism (rBGM) and gray matter (GM) volume in retired soccer players (RSPs). Methods Male RSPs and age and sex-matched controls prospectively enrolled between 2017 and 2019 underwent neurological and neuropsychological evaluations, brain MRI and [18F]FDG-PET in a 3.0-Tesla PET/MRI scanner. Visual analysis was performed by a blinded neuroradiologist and a blinded nuclear physician. Regional brain glucose metabolism and GM volume were assessed using SPM8 software. Groups were compared using appropriate statistical tests available at SPM8 and R. Results Nineteen RSPs (median [IQR]: 62 [50-64.5] years old) and 20 controls (60 [48-73] years old) were included. Retired soccer players performed worse on mini-mental state examination, digit span, clock drawing, phonemic and semantic verbal fluency tests, and had reduced rBGM in the left temporal pole (pFDR = 0.008) and the anterior left middle temporal gyrus (pFDR = 0.043). Semantic verbal fluency correlated with rBGM in the right hippocampus, left temporal pole, and posterior left middle temporal gyrus (p ≤ 0.042). Cray matter volume reduction was observed in similar anatomic regions but was less extensive and did not survive correction for multiple comparisons (pFDR ≥ 0.085). Individual [18F]FDG-PET visual analysis revealed seven RSPs with overt hypometabolism in the medial and lateral temporal lobes, frontal lobes, and temporoparietal regions. Retired soccer players had a higher prevalence of septum pellucidum abnormalities on MRI. Conclusion Retired soccer players had reduced rBCM and CM volume in the temporal lobes and septum pellucidum abnormalities, findings possibly related to repetitive head impacts.

Resumo Antecedentes Jogadores profissionais de futebol estão expostos a impactos cranianos repetitivos e ao risco de desenvolver encefalopatia traumática crônica. Objetivo Avaliar o metabolismo glicolítico cerebral regional (MCCr) e o volume de substância cinzenta (vSC) em jogadores de futebol aposentados (JFAs). Métodos Jogadores de futebol aposentados masculinos e controles pareados por idade e sexo foram incluídos prospectivamente entre 2017 e 2019. Foram realizadas avaliações neurológica e neuropsicológica, ressonância magnética (RM) e [18F]FDG-PET cerebrais (3.0-Tesla PET/RM). As imagens foram analisadas visualmente por um neurorradiologista e um médico nuclear cegos ao grupo de cada participante. O metabolismo glicolítico cerebral regional e o vSC foram avaliados através do programa SPM8. Os grupos foram comparados através de testes estatísticos apropriados disponíveis em SPM8 e R, de acordo com a distribuição e o tipo dos dados. Resultados Dezenove JFAs (mediana [IIQ]: 62 [50-64.5] anos) e 20 controles (60 [48-73] anos) foram incluídos. Os JFAs tiveram pior desempenho no mini-exame do estado mental e nos testes de dígitos, desenho do relógio, fluência verbal e fluência semântica e apresentaram MCCr significativamente reduzido no polo temporal e no giro temporal médio anterior esquerdos. Fluência semântica (animais) apresentou correlação positiva com MCCr no hipocampo direito, no polo temporal esquerdo e no aspecto posterior do giro temporal médio esquerdo. Menor vSC foi observado nas mesmas regiões, porém este achado não sobreviveu à correção para comparações múltiplas. Análise individual do [18F]FDG-PET cerebral revelou sete JFAs com claro hipometabolismo nas faces medial e lateral dos lobos temporais, nos lobos frontais e nas regiões temporoparietais. Os JFAs apresentaram ainda maior prevalência de anormalidades do septo pelúcido. Conclusão Os JFAs apresentam MCCr e vSC reduzidos nos lobos temporais, além de anormalidades do septo pelúcido, achados possivelmente relacionados a impactos cranianos repetitivos.

99mTc-HYNIC/Cy7-Fab(Bevacizumab): su empleo como agente de imagen en mieloma múltiple / 99mTc-HYNIC/Cy7-Fab(Bevacizumab): its use as an imaging agent in Multiple Myeloma / 99mTc-HYNIC/Cy7-Fab (Bevacizumab): seu uso como agente de imagem em mieloma múltiplo

Introducción: el mieloma múltiple es un trastorno hematológico maligno y el segundo cáncer de la sangre más frecuente. El proceso de la angiogénesis tumoral es fundamental para el crecimiento y metástasis de muchos tipos de tumores, incluido en mieloma múltiple. Se sabe que la sobreexpresión del factor de crecimiento endothelial vascular se encuentra asociado a un mal pronóstico en esta patología, representando un blanco clave para la terapia anti-angiogénica en mieloma múltiple. El anticuerpo monoclonal Bevacizumab es capaz de unirse con gran afinidad al factor de crecimiento endothelial vascular bloqueando su acción. Objetivo: evaluar el Fab(Bevacizumab) marcado con 99mTc o Cy7 como potenciales agentes de imagen moleculares de la expresión de factor de crecimiento endothelial vascular en mieloma múltiple. Material y métodos: la expresión de factor de crecimiento endothelial vascular fue analizada mediante citometría de flujo en la línea celular huaman de mieloma múltiple, la MM1S. Fab(Bevacizumab) fue producido mediante digestión de Bevacizumab con papaína, conjugado a NHS-HYNIC-Tfa y radiomarcado con 99mTc. Se realizaron estudios de biodistribución y de tomografía computarizada por emisión del fotón simple. A su vez, Fab(Bevacizumab) fue marcado con Cy7 para obtener imágenes de fluorescencia in vivo hasta 96 horas. Resultados: el análisis por citometría de flujo en la línea celular MM1S reveló que la expresión de factor de crecimiento endothelial vascular es predominantemente intracelular. Los estudios de biodistribución y SPECT/CT del complejo 99mTc-HYNIC-Fab(Bevacizumab) mostraron una rápida eliminación sanguínea y una significativa captación a nivel renal y tumoral. Las imágenes por fluorescencia empleando Cy7-Fab(Bevacizumab) permitieron la visualización tumoral hasta 96 h p.i. Conclusiones: logramos visualizar la expresión de factor de crecimiento endothelial vascular in vivo en mieloma múltiple mediante el empleo del fragmento Fab del anticuerpo anti-VEGF (Bevacizumab) marcado con 99mTc y Cy7. Estos nuevos agentes de imagen molecular podrían ser empleados potencialmente en el ámbito clínico para la estadificación y el seguimiento de pacientes con mieloma múltiple, mediante la visualización radioactiva in vivo de la expresión de factor de crecimiento endothelial vascular en todo el cuerpo. La imagen óptica de estos trazadores mejoraría el muestreo tumoral y podría guiar la extirpación quirúrgica.

Introduction: Multiple myeloma is a hematologic malignancy and the second most common blood cancer. The process of tumor angiogenesis is central to the growth and metastasis of many types of tumors, including multiple myeloma. Overexpression of vascular endothelial growth factor is known to be associated with poor prognosis in this pathology, representing a key target for anti-angiogenic therapy in multiple myeloma. The monoclonal antibody Bevacizumab is able to bind with high affinity to vascular endothelial growth factor blocking its action. Objective: to evaluate 99mTc- or Cy7-labeled Fab(Bevacizumab) as potential molecular imaging agents of vascular endothelial growth factor expression in multiple myeloma. Methods: Vascular endothelial growth factor expression was analyzed by flow cytometry in the multiple myeloma huaman cell line, MM1S. Fab(Bevacizumab) was produced by digestion of Bevacizumab with papain, conjugated to NHS-HYNIC-Tfa and radiolabeled with 99mTc. Biodistribution and single photon emission computed tomography studies were performed. In turn, Fab(Bevacizumab) was labeled with Cy7 to obtain in vivo fluorescence images up to 96 hours. Results: Flow cytometry analysis in the MM1S cell line revealed that vascular endothelial growth factor expression is predominantly intracellular. Biodistribution and SPECT/CT studies of the 99mTc-HYNIC-Fab(Bevacizumab) complex showed rapid blood clearance and significant renal and tumor uptake. Fluorescence imaging using Cy7-Fab(Bevacizumab) allowed tumor visualization up to 96 h p.i. Conclusions: we were able to visualize vascular endothelial growth factor expression in vivo in multiple myeloma using the Fab fragment of the anti-VEGF antibody (Bevacizumab) labeled with 99mTc and Cy7. These new molecular imaging agents could potentially be employed in the clinical setting for staging and monitoring of patients with multiple myeloma by in vivo radioactive visualization of vascular endothelial growth factor expression throughout the body. Optical imaging of these tracers would improve tumor sampling and could guide surgical excision.

Introdução: O mieloma múltiplo é uma malignidade hematológica e o segundo câncer de sangue mais comum. O processo de angiogênese tumoral é fundamental para o crescimento e a metástase de muitos tipos de tumores, incluindo o mieloma múltiplo. Sabe-se que a superexpressão do fator de crescimento endotelial vascular está associada a um prognóstico ruim no mieloma múltiplo, representando um alvo importante para a terapia antiangiogênica no mieloma múltiplo. O anticorpo monoclonal Bevacizumab é capaz de se ligar com alta afinidade ao fator de crescimento endotelial vascular e bloquear sua ação. Objetivo: avaliar o Fab(Bevacizumab) marcado com 99mTc ou Cy7 como possíveis agentes de imagem molecular da expressão do fator de crescimento endotelial vascular no mieloma múltiplo. Métodos: A expressão do fator de crescimento endotelial vascular foi analisada por citometria de fluxo na linha celular de mieloma múltiplo MM1S. O Fab(Bevacizumab) foi produzido pela digestão do Bevacizumab com papaína, conjugado com NHS-HYNIC-Tfa e radiomarcado com 99mTc. Foram realizados estudos de biodistribuição e tomografia computadorizada por emissão de fóton único. Por sua vez, o Fab(Bevacizumab) foi marcado com Cy7 para geração de imagens de fluorescência in vivo por até 96 horas. Resultados: A análise de citometria de fluxo na linha celular MM1S revelou que a expressão do fator de crescimento endotelial vascular é predominantemente intracelular. Os estudos de biodistribuição e SPECT/CT do complexo 99mTc-HYNIC-Fab(Bevacizumab) mostraram uma rápida depuração sanguínea e uma captação renal e tumoral significativa. A imagem de fluorescência usando Cy7-Fab(Bevacizumab) permitiu a visualização do tumor até 96 horas p.i. Conclusões: Conseguimos visualizar a expressão do fator de crescimento endotelial vascular in vivo no mieloma múltiplo usando o fragmento Fab do anticorpo anti-VEGF (Bevacizumab) marcado com 99mTc e Cy7. Esses novos agentes de imagem molecular poderiam ser usados no cenário clínico para o estadiamento e o monitoramento de pacientes com mieloma múltiplo, visualizando radioativamente a expressão do fator de crescimento endotelial vascular in vivo em todo o corpo. A geração de imagens ópticas desses traçadores melhoraria a amostragem do tumor e poderia orientar a excisão cirúrgica.

Radiation safety measures in diagnostic nuclear medicine, based on the potential radiation dose emitted by radioactive patients / Cuidados de radioproteção em medicina nuclear diagnóstica baseados no potencial de dose de radiação emitida por pacientes radioativos

Abstract Objective: To measure the potential radiation dose emitted by patients who have recently undergone diagnostic nuclear medicine procedures, in order to establish optimal radiation safety measures for such procedures. Materials and Methods: We evaluated the radiation doses emitted by 175 adult patients in whom technetium-99m, iodine-131, and fluorine-18 radionuclides were administered for bone, kidney, heart, brain, and whole-body scans, as measured with a radiation detector. Those values served as the basis for evaluating whole-body radiopharmaceutical clearance, as well as the risk for the exposure of others to radiation, depending on the time elapsed since administration of the radiopharmaceutical. Results: The mean time to clearance of the radiopharmaceuticals administered, expressed as the effective half-life, ranged from 1.18 ± 0.30 h to 11.41 ± 0.02 h, and the mean maximum cumulative radiation dose at 1.0 m from the patients was 149.74 ± 56.72 µSv. Even at a distance of 0.5 m, the cumulative dose was found to be only half and one tenth of the limits established for exposure of the general public and family members/caregivers (1.0 mSv and 5.0 mSv per episode, respectively). Conclusion: Cumulative radiation doses emitted by patients immediately after diagnostic nuclear medicine procedures are considerably lower than the limits established by the International Commission on Radiological Protection and the International Atomic Energy Agency, and precautionary measures to avoid radiation exposure are therefore not required after such procedures.

Resumo Objetivo: O objetivo deste trabalho foi levantar o potencial de dose de radiação emitida por pacientes em procedimentos diagnósticos, visando a estabelecer cuidados de radioproteção mais otimizados. Materiais e Métodos: Taxas de dose de radiação emitidas por 175 pacientes administrados com os radionuclídeos 99mTc, 131I e 18F para cintilografias óssea, renal, cardíaca, cerebral e corpo inteiro, foram mensuradas com um detector de radiação, servindo para avaliar o clareamento do radiofármaco no organismo e risco de exposição após administração dos radiofármacos. Resultados: O clareamento, representado pela meia-vida efetiva, variou de 1,18 ± 0,30 h até 11,41 ± 0,02 h e a dose de radiação máxima acumulada oferecida pelos pacientes a 1,0 m foi de 149,74 ± 56,72 µSv. Mesmo para distâncias de 0,5 m, as doses estimadas foram, respectivamente, duas e dez vezes inferiores ao nível de restrição para o público geral (1,0 mSv) e exposição médica (5,0 mSv/episódio). Conclusão: Doses de radiação oferecidas por pacientes em procedimentos diagnósticos são inferiores aos níveis de restrição recomendados pela International Commission on Radiological Protection e International Atomic Energy Agency, e assim, cuidados de radioproteção são geralmente desnecessários.

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.

18F-FDG-PET/CT-measured parameters as potential predictors of residual disease after neoadjuvant chemoradiotherapy in patients with esophageal carcinoma / 18F-FDG-PET/CT após quimiorradioterapia neoadjuvante em pacientes com carcinoma de esôfago como potencial preditor de doença residual

Abstract Objective: To evaluate the maximum and mean standardized uptake values, together with the metabolic tumor value and the total lesion glycolysis, at the primary tumor site, as determined by 18F-fluorodeoxyglucose positron-emission tomography/computed tomography (18F-FDG-PET/CT), performed before and after neoadjuvant chemoradiotherapy (nCRT), as predictors of residual disease (RD) in patients with esophageal cancer. Materials and Methods: The standardized uptake values and the volumetric parameters (metabolic tumor value and total lesion glycolysis) were determined by 18F-FDG-PET/CT to identify RD in 39 patients before and after nCRT for esophageal carcinoma. We used receiver operating characteristic curves to analyze the diagnostic performance of 18F-FDG-PET/CT parameters in the definition of RD. The standard of reference was histopathological analysis of the surgical specimen. Results: Eighteen patients (46%) presented RD after nCRT. Statistically significant areas under the curve (approximately 0.72) for predicting RD were obtained for all four of the variables evaluated after nCRT. Considering the presence of visually detectable uptake (higher than the background level) at the primary tumor site after nCRT as a positive result, we achieved a sensitivity of 94% and a specificity of 48% for the detection of RD. Conclusion: The use of 18F-FDG-PET/CT can facilitate the detection of RD after nCRT in patients with esophageal cancer.

Resumo Objetivo: Avaliar os valores máximo e médio de captação padronizada, o valor metabólico do tumor e a glicólise total da lesão do local do tumor primário, medidos no estudo de 18F-FDG-PET/CT realizado antes e depois da quimiorradioterapia neoadjuvante (nQRT) em pacientes com câncer de esôfago, como preditores de doença residual (DR). Materiais e Métodos: Os valores máximo e médio de captação padronizada e os parâmetros volumétricos (valor metabólico do tumor e glicólise total da lesão) da 18F-FDG-PET/CT realizada em 39 pacientes antes e após a nQRT para carcinoma de esôfago foram avaliados para RD. Usamos curvas receiver operating characteristic (ROC) para analisar o desempenho diagnóstico dos parâmetros 18F-FDG-PET/CT na definição de RD. O estudo anatomopatológico foi utilizado como padrão ouro. Resultados: Dezoito pacientes (46%) apresentaram DR após a nQRT. Áreas estatisticamente significativas sob a curva ROC para predizer DR foram obtidas para as quatro variáveis nos estudos realizados após a nQRT, com áreas sob a curva ROC semelhantes em torno de 0,72. Considerando a presença de captação visualmente detectável (captação maior que o background) no local da lesão primária após a nQRT como resultado positivo, teríamos uma sensibilidade de 94% e uma especificidade de 48% para detecção de DR. Conclusão: A 18F-FDG-PET/CT pode ser útil para detectar a presença de doença neoplásica residual no câncer de esôfago após a nQRT.

Does [18F]F-FDG-PET/MRI add metabolic information to magnetic resonance image in childhood-onset Takayasu's arteritis patients? A multicenter case series

Abstract Background: The observation that 2-deoxy-2[18F]fluoro-D-glucose-positron emission tomography/magnetic resonance imaging ([18F]F-FDG-PET/MRI) revealed high-grade arterial wall FDG uptake, without arterial wall thickening with contrast-enhancement, in a considerable number of c-TA patients in our previous study, encouraged us to compare patients with both PET and MR angiography (MRA) positives, with those with PET positive but MRA negative. Our aim was to evaluate the relevance of these two imaging modalities together. Methods: A three-center cross-sectional study with 17 patients who fulfilled the EULAR/PRINTO/PReS criteria for c-TA and who underwent [18F]F-FDG-PET/MRI was previously performed. Herein we compared patients/vessels with positive PET (arterial wall 18F-FDG uptake higher than liver) and positive MRA (arterial wall thickening with contrast-enhancement)—group 1, with those with positive PET but negative MRA—group 2. Results: Median disease duration of 17 c-TA patients was 10.4 years. Nine patients were classified as group 1 and six as group 2. Median of metabolic inflammatory volume (MIV) of all arterial segments was significantly higher in group 1 (2346 vs. 1177 cm3; p = 0.036). Fifty-four (19%) from 284 available arterial segments presented positive findings in vessel wall in one or both images. Positive findings were concordant between PET and MRA in only 13% arterial segments (group 1); most changes (28-59.6%) that were discordant between both images, were positive in PET and negative in MRA (group 2). Conclusions: Our study demonstrated that [18F]F-FDG-PET/MRI added information about inflammation in vessel wall of c-TA patients. Prospective multicenter studies are needed in order to get solid data to guide immunosuppressive tapering and withdrawal.

Persistent symptoms and decreased health-related quality of life after symptomatic pediatric COVID-19: A prospective study in a Latin American tertiary hospital

OBJECTIVES: To prospectively evaluate demographic, anthropometric and health-related quality of life (HRQoL) in pediatric patients with laboratory-confirmed coronavirus disease 2019 (COVID-19) METHODS: This was a longitudinal observational study of surviving pediatric post-COVID-19 patients (n=53) and pediatric subjects without laboratory-confirmed COVID-19 included as controls (n=52) was performed. RESULTS: The median duration between COVID-19 diagnosis (n=53) and follow-up was 4.4 months (0.8-10.7). Twenty-three of 53 (43%) patients reported at least one persistent symptom at the longitudinal follow-up visit and 12/53 (23%) had long COVID-19, with at least one symptom lasting for >12 weeks. The most frequently reported symptoms at the longitudinal follow-up visit were headache (19%), severe recurrent headache (9%), tiredness (9%), dyspnea (8%), and concentration difficulty (4%). At the longitudinal follow-up visit, the frequencies of anemia (11% versus 0%, p=0.030), lymphopenia (42% versus 18%, p=0.020), C-reactive protein level of >30 mg/L (35% versus 0%, p=0.0001), and D-dimer level of >1000 ng/mL (43% versus 6%, p=0.0004) significantly reduced compared with baseline values. Chest X-ray abnormalities (11% versus 2%, p=0.178) and cardiac alterations on echocardiogram (33% versus 22%, p=0.462) were similar at both visits. Comparison of characteristic data between patients with COVID-19 at the longitudinal follow-up visit and controls showed similar age (p=0.962), proportion of male sex (p=0.907), ethnicity (p=0.566), family minimum monthly wage (p=0.664), body mass index (p=0.601), and pediatric pre-existing chronic conditions (p=1.000). The Pediatric Quality of Live Inventory 4.0 scores, median physical score (69 [0-100] versus 81 [34-100], p=0.012), and school score (60 [15-100] versus 70 [15-95], p=0.028) were significantly lower in pediatric patients with COVID-19 at the longitudinal follow-up visit than in controls. CONCLUSIONS: Pediatric patients with COVID-19 showed a longitudinal impact on HRQoL parameters, particularly in physical/school domains, reinforcing the need for a prospective multidisciplinary approach for these patients. These data highlight the importance of closer monitoring of children and adolescents by the clinical team after COVID-19.

Preserved repetition in thalamic afasia. A pathophysiological hypothesis / Preservação da repetição na afasia talâmica. Uma hipótese fisiopatológica

ABSTRACT. The ability to repeat words is almost always preserved in thalamic aphasia. The pathophysiology of both thalamic aphasia and preservation of repetition are not fully understood. In a case of severe aphasia with preserved repetition after a left thalamic hemorrhage, MRI disclosed left thalamic lesion and loss of fractional anisotropy in the left centrum semiovale. FDG-PET showed severe hypometabolism in the left cerebral hemisphere, except for superior and transverse temporal gyri, calcarine fissure and frontopolar regions. Primary sensory function may be less functionally dependent on thalamic connections than heteromodal and paralimbic areas, which have connections with several thalamic nuclei. The extensive cortical hypometabolism due to diaschisis may have been responsible for the severity of the aphasia, whereas the less severe reduction of metabolism in the superior and transverse temporal gyri, and also, albeit less evident, in Broca's area, might explain the preservation of repetition.

RESUMO. A capacidade de repetir palavras é quase sempre preservada na afasia talâmica. A fisiopatologia da afasia talâmica assim como a da preservação da repetição não são totalmente compreendidas. Em um caso de afasia grave com repetição preservada após hemorragia talâmica esquerda, a RM revelou lesão talâmica esquerda e perda de anisotropia fracionada no centro semioval. O FDG-PET revelou hipometabolismo grave no hemisfério cerebral esquerdo, exceto nos giros temporais superiores e transversos, fissura calcarina e regiões frontopares. A função sensorial primária pode ser menos funcionalmente dependente das conexões talâmicas do que as áreas heteromodais e paralímbicas, que têm conexões com vários núcleos talâmicos. O hipometabolismo cortical extenso devido à diasquise pode ter sido responsável pela gravidade da afasia, enquanto a redução menos severa do metabolismo nos giros temporal superior e transverso, e também, embora menos evidente, na área de Broca, poderia explicar a preservação da repetição.

Topography of 11C-Pittsburgh compound B uptake in Alzheimer's disease: a voxel-based investigation of cortical and white matter regions

Objective: To compare results of positron emission tomography (PET) with carbon-11-labeled Pittsburgh compound B (11C-PIB) obtained with cerebellar or global brain uptake for voxel intensity normalization, describe the cortical sites with highest tracer uptake in subjects with mild Alzheimer's disease (AD), and explore possible group differences in 11C-PIB binding to white matter. Methods: 11C-PIB PET scans were acquired from subjects with AD (n=17) and healthy elderly controls (n=19). Voxel-based analysis was performed with statistical parametric mapping (SPM). Results: Cerebellar normalization showed higher 11C-PIB uptake in the AD group relative to controls throughout the cerebral cortex, involving the lateral temporal, orbitofrontal, and superior parietal cortices. With global uptake normalization, greatest cortical binding was detected in the orbitofrontal cortex; decreased 11C-PIB uptake in white matter was found in the posterior hippocampal region, corpus callosum, pons, and internal capsule. Conclusion: The present case-control voxelwise 11C-PIB PET comparison highlighted the regional distribution of amyloid deposition in the cerebral cortex of mildly demented AD patients. Tracer uptake was highest in the orbitofrontal cortex. Decreased 11C-PIB uptake in white-matter regions in this patient population may be a marker of white-matter damage in AD.

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.

Value of ultrasound in the anatomical evaluation of the brachial plexus: correlation with magnetic resonance imaging / Valor da ultrassonografia na avaliação anatômica do plexo braquial por meio da correlação com estudo por ressonância magnética

Abstract Objective: To assess the accuracy of ultrasound in the visualization of the brachial plexus and to determine the value of the method in comparison with that of magnetic resonance imaging (MRI). Materials and Methods: This was an anatomical study of the brachial plexuses of 20 asymptomatic adults (40 plexuses), comparing ultrasound and MRI in terms of their accuracy. In the ultrasound study, a high-frequency linear transducer was used, and a neurovascular coil was used in the MRI study. To estimate the frequency of visualization, the brachial plexus was divided into segments. Results: The cervical nerve roots, the upper trunk, and the middle trunk were the segments that were best visualized on ultrasound. On MRI, the degree of visualization was excellent for most of the segments. In the comparison between ultrasound and MRI, the C6, C7, upper trunk, and middle trunk segments showed equivalent degrees of visualization, with a high level of agreement between the two methods. Conclusion: In the brachial plexus, ultrasound can be used in the assessment of the cervical nerve roots, as well as of the upper and middle trunks, although it provides limited visualization of the remaining segments. Ultrasound and MRI showed a high level of agreement for the visualization of the C6, C7, and middle trunk segments.

Resumo Objetivo: Avaliar a eficácia do exame de ultrassonografia (US) na visualização do plexo braquial e avaliar o método comparativamente à ressonância magnética (RM). Materiais e Métodos: Estudo da anatomia do plexo braquial pela US e RM (40 plexos braquiais) em 20 adultos assintomáticos. No estudo por US foi utilizado transdutor linear de alta frequência e na RM de alto campo magnético foi utilizada bobina neurovascular. O plexo braquial foi dividido em segmentos para estimar a frequência da visualização entre a US e a RM. Resultados: As raízes cervicais e os troncos superior e médio foram as estruturas que apresentaram maior grau de visualização pela US. Na RM, a maioria dos segmentos do plexo apresentou excelente grau de visualização. Na análise da equivalência entre a US e a RM, as raízes de C5, C6, tronco superior e médio apresentaram graus de visualização equivalentes, com alta concordância. Conclusão: O método de US consegue avaliar de forma eficaz o segmento proximal do plexo braquial que compreende as saídas das raízes cervicais de C5, C6 e C7, assim como os troncos superior e médio na região lateral do pescoço. O exame de US mostrou ter alta concordância com a RM nos ramos ventrais cervicais de C6, C7 e o tronco médio bilateral.

Prognostic value of focal scintigraphic findings in clinically suspected cases of tibial stress fracture / Valor prognóstico dos achados focais na cintilografia óssea em pacientes suspeitos de fratura por estresse na tíbia

Abstract Objective: To investigate the correlation between tracer uptake on bone scintigraphy and recovery time in patients with tibial stress fracture. Materials and Methods: We evaluated two groups of athletes: those with clinical suspicion and a radiological diagnosis of tibial stress fracture (TSF group, n = 21); and those with no symptoms or evidence of fracture (control group, n = 10). All subjects underwent bone scintigraphy and magnetic resonance imaging with a maximum interval of 7 days between the assessments. Results: Using the region of interest technique, we obtained a quantitative evaluation index, comparing affected and unaffected legs. The mean uptake of 99mTc-MDP was significantly higher in the TSF group than in the control group (2.54 ± 0.77 vs. 1.05 ± 0.11; p < 0.001). Conclusion: In our sample of athletes, determining the bone scintigraphy uptake indices provided an objective method to estimate the appropriate recovery time after a tibial stress fracture.

Resumo Objetivo: Analisar a correlação entre a captação da cintilografia óssea e o tempo para recuperação de pacientes com fraturas de estresse na tíbia. Materiais e Métodos: Foram avaliados 21 atletas com suspeita clínica e o diagnóstico radiológico de fratura por estresse na tíbia (grupo 1) e 10 atletas assintomáticos (grupo 2). Todos os sujeitos submeteram-se a cintilografia óssea e ressonância magnética com intervalo máximo de sete dias entre as avaliações. Resultados: Índice quantitativo foi obtido usando a técnica da região de interesse, comparando pernas afetadas com não afetadas. A média de captação do 99mTc-MDP nos membros afetados foi significativamente diferente no grupo 1 (2,54 ± 0,77), comparado com o grupo 2 (1,05 ± 0,11) (p < 0,001). Conclusão: Em nossa amostra de atletas, os índices de captação obtidos pela cintilografia óssea proporcionaram um método objetivo para estimar o tempo de recuperação apropriado após uma fratura de estresse na tíbia.

Support vector machine-based classification of neuroimages in Alzheimer's disease: direct comparison of FDG-PET, rCBF-SPECT and MRI data acquired from the same individuals

Objective: To conduct the first support vector machine (SVM)-based study comparing the diagnostic accuracy of T1-weighted magnetic resonance imaging (T1-MRI), F-fluorodeoxyglucose-positron emission tomography (FDG-PET) and regional cerebral blood flow single-photon emission computed tomography (rCBF-SPECT) in Alzheimer's disease (AD). Method: Brain T1-MRI, FDG-PET and rCBF-SPECT scans were acquired from a sample of mild AD patients (n=20) and healthy elderly controls (n=18). SVM-based diagnostic accuracy indices were calculated using whole-brain information and leave-one-out cross-validation. Results: The accuracy obtained using PET and SPECT data were similar. PET accuracy was 68∼71% and area under curve (AUC) 0.77∼0.81; SPECT accuracy was 68∼74% and AUC 0.75∼0.79, and both had better performance than analysis with T1-MRI data (accuracy of 58%, AUC 0.67). The addition of PET or SPECT to MRI produced higher accuracy indices (68∼74%; AUC: 0.74∼0.82) than T1-MRI alone, but these were not clearly superior to the isolated neurofunctional modalities. Conclusion: In line with previous evidence, FDG-PET and rCBF-SPECT more accurately identified patients with AD than T1-MRI, and the addition of either PET or SPECT to T1-MRI data yielded increased accuracy. The comparable SPECT and PET performances, directly demonstrated for the first time in the present study, support the view that rCBF-SPECT still has a role to play in AD diagnosis.

Bone marrow uptake of 18F-fluorodeoxyglucose in Hodgkin lymphoma without bone involvement: comparison between patients with and without B symptoms / Captação de 18F fluordesoxiglicose na medula óssea em pacientes com linfoma de Hodgkin sem comprometimento ósseo: comparação entre pacientes com e sem sintomas B

Abstract Objective: To compare the degree of benign bone marrow uptake of 18F-fluorodeoxyglucose (18F-FDG) between Hodgkin lymphoma patients with and without B symptoms. Materials and Methods: We analyzed the medical charts of 74 Hodgkin lymphoma patients who underwent 18F-FDG positron emission tomography/computed tomography (PET/CT) prior to the initiation of therapy between October 2010 and September 2013. In all of the patients, the bone marrow biopsy was negative and the 18F-FDG PET/CT images did not suggest bone marrow involvement. Of the 74 patients evaluated, 54 presented inflammatory (B) symptoms and 20 did not. Regions of interest (ROIs) were drawn on the sternum, the proximal thirds of the humeri, the proximal thirds of the femora, and both iliac wings (totaling seven ROIs per patient). To compare the patients with and without B symptoms, in terms of standardized uptake values (SUVs) for the seven ROIs, we used the Mann-Whitney U test. Results: For six of the ROIs, the SUVs were higher in the patients with B symptoms than in those without, and the difference was statistically significant (p < 0.05). There was also a tendency toward a statistically significant difference between the two groups in terms of the SUV for the right iliac wing ROI (p = 0.06). Conclusion: In our sample, the presence of B symptoms was associated with increased 18F-FDG uptake in bone marrow.

Resumo Objetivo: Comparar o grau de absorção benigna de 18F-fluordesoxiglicose (18F-FDG) na medula óssea de pacientes com linfoma de Hodgkin com e sem sintomas B. Materiais e Métodos: Analisamos os prontuários de 74 pacientes com linfoma de Hodgkin submetidos a tomografia por emissão de pósitrons/tomografia computadorizada (PET/CT) com 18F-FDG antes do início da terapia entre outubro de 2010 e setembro de 2013. Em todos os pacientes, a biópsia da medula óssea foi negativa e as imagens de 18F-FDG PET/CT não sugeriram envolvimento da medula óssea. Dos 74 pacientes avaliados, 54 apresentaram sintomas inflamatórios (B) e 20 não. As regiões de interesse (ROIs) foram desenhadas no esterno, nos terços proximais dos úmeros, nos terços proximais dos fêmures e nas duas asas ilíacas (totalizando sete ROIs por paciente). Para comparar os pacientes com e sem sintomas B, em termos dos standardized uptake values (SUVs) para as sete ROIs, utilizamos o teste U de Mann-Whitney. Resultados: Para seis das ROIs, os SUVs foram maiores nos pacientes com sintomas B do que nos pacientes sem, e a diferença foi estatisticamente significante (p < 0,05). Houve também tendência para uma diferença estatisticamente significante entre os dois grupos em termos do SUV para a ROI da asa ilíaca direita (p = 0,06). Conclusão: Na nossa amostra, a presença de sintomas B foi associada ao aumento da captação de 18F-FDG na medula óssea.

Positron emission tomography/magnetic resonance imaging (PET/MRI): An update and initial experience at HC-FMUSP / Tomografia por emissão de pósitrons/ressonância magnética (PET/RM): atualização e experiência inicial do HC-FMUSP

Summary The new technology of PET/MRI is a prototype of hybrid imaging, allowing for the combination of molecular data from PET scanning and morphofunctional information derived from MRI scanning. Recent advances regarding the technical aspects of this device, especially after the development of MRI-compatible silicon photomultipliers of PET, permitted an increase in the diagnostic performance of PET/MRI translated into dose reduction and higher imaging quality. Among several clinical applications, PET/MRI gains ground initially in oncology, where MRI per se plays an essential role in the assessment of primary tumors (which is limited in the case of PET/CT), including prostate, rectal and gynecological tumors. On the other hand, the evaluation of the lungs remains an enigma although new MRI sequences are being designed to overcome this. More clinical indications of PET/MRI are seen in the fields of neurology, cardiology and inflammatory processes, and the use of PET/MRI also opens perspectives for pediatric populations as it involves very low radiation exposure. Our review aimed to highlight the current indications of PET/MRI and discuss the challenges and perspectives of PET/MRI at HC-FMUSP.

Resumo A nova tecnologia PET/RM é o protótipo de diagnóstico por imagem híbrido e permite combinar dados moleculares obtidos da tomografia PET e informações morfofuncionais derivadas da ressonância magnética. Avanços recentes relativos a aspectos técnicos desse dispositivo, principalmente após o desenvolvimento de fotomultiplicadores de silício compatíveis com RM, permitiram uma melhora do desempenho diagnóstico da PET/RM traduzida em redução da dose e qualidade superior das imagens. Entre diversas aplicações clínicas, a PET/RM ganha espaço inicialmente no campo da oncologia, onde a RM tem papel essencial na avaliação de tumores primários (limitado no caso da PET/TC), incluindo tumores de próstata, reto e ginecológicos. Por outro lado, a avaliação dos pulmões ainda é um enigma, a despeito de novas sequências de RM que estão sendo criadas para tentar resolver essa questão. Outras indicações clínicas da PET/RM são encontradas no âmbito da neurologia, cardiologia e de processos inflamatórios, nos quais a técnica também abre perspectivas para pacientes pediátricos, já que envolve uma exposição baixíssima à radiação. Nossa revisão teve como objetivo destacar as indicações atuais da PET/RM e discutir os desafios e perspectivas da aplicação dessa técnica no Hospital das Clínicas da FMUSP.

Clinical perspectives of PSMA PET/MRI for prostate cancer

Prostate cancer imaging has become an important diagnostic modality for tumor evaluation. Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) has been extensively studied, and the results are robust and promising. The advent of the PET/magnetic resonance imaging (MRI) has added morphofunctional information from the standard of reference MRI to highly accurate molecular information from PET. Different PSMA ligands have been used for this purpose including 68gallium and 18fluorine-labeled PET probes, which have particular features including spatial resolution, imaging quality and tracer biodistribution. The use of PSMA PET imaging is well established for evaluating biochemical recurrence, even at low prostate-specific antigen (PSA) levels, but has also shown interesting applications for tumor detection, primary staging, assessment of therapeutic responses and treatment planning. This review will outline the potential role of PSMA PET/MRI for the clinical assessment of PCa.

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.