Tomografia computadorizada por emissão de pósitrons para pacientes com câncer de pulmão de células pequenas / Computed tomography by positron emission for patients with small cell lung cancer

INTRODUÇÃO: De acordo com as estimativas mais recentes do INCA para o triênio de 2023 a 2025, no Brasil, aponta-se para a ocorrência de 704 mil casos novos de câncer, dos quais 32 mil de câncer de pulmão (4,6%). Cerca de 15% dos casos correspondem ao câncer de pulmão de células pequena (CPCP). Setenta por cento dos pacientes já se se apresentam com doença avançada ao diagnóstico, de pior prognóstico, devido ao rápido crescimento e à capacidade marcante de desenvolver metástases precoces dessa doença. Atualmente, na prática clínica, ainda é utilizada uma classificação antiga que distingue o CPCP em doença limitada (CPCP-DL) e doença extensa (CPCP-DE). Desta forma, uma vez obtida a confirmação da malignidade e do tipo histopatológico tumoral, procede-se ao estadiamento clínico, que no SUS acontece por meio de tomografia computadorizada de tórax e abdome superior, com contraste, cintilografia óssea com Tecnécio-99m e ressonância magnética do cérebro. O PET-CT, é um exame de imagem que pode ser usado como parte da investigação de estadiamento em pacientes com CPCP. Atualmente, o PET-CT é indicado para o estadiamento do câncer de pulmão de células não pequenas potencialmente ressecável. Entretanto, para a atualização da DDT de Câncer de Pulmão, apontou-se a necessidade de ampliação do uso deste procedimento para os pacientes com CPCP. PERGUNTA DE PESQUISA: Em pacientes com câncer de pulmão de células pequenas, qual a sensibilidade, especificidade, segurança, custo-efetividade e impacto orçamentário da PET-CT em comparação às alternativas disponíveis no SUS (tomografia computadorizada, cintilografia óssea e ressonância magnética do cérebro) para o estadiamento tumoral? SÍNTESE DE EVIDÊNCIA CLÍNICA: Foram incluídos quatro estudos observacionais retrospectivos e um estudo prospectivo nos quaisse avaliou o PET-CT para estadiamento do CPCP. Pelo contexto de teste de referência imperfeito, mix de testes de referência (TC, RM e CT) e elevada heterogeneidade do mix de testes e dos desfechos não foi possível realizar meta-análise de acurácia ou proporção, bem como análise narrativa de acurácia. Assim, considerando as limitações metodológicas apontadas acima, apresentou-se como resultado o desfecho mudança no estadiamento após avaliação por PET-CT de pacientes previamente estadiados por outros métodos. Julgou-se que esse desfecho é importante, pois pode afetar o gerenciamento terapêutico e o prognóstico do paciente. Quando não reportada, esta medida foi calculada pelos autores do relatório. Nos cinco estudos avaliados a utilização de PET-CT (18F-FDG PET/CT) em relação a TC, RM e CT permitiu a correta reclassificação de estádio dos pacientes em 10% a 47% dos casos. Observou-se na maioria dos casos o reestadiamento de doença localizada para doença extensiva pela identificação de metástases não detectadas pelos métodos avaliados como comparadores. O reestadiamento permitiu, como se relatou em alguns dos estudos, a modificação da conduta terapêutica. AVALIAÇÃO ECONÔMICA: Na análise de custo-efetividade demonstrou-se que a ampliação do uso da PET-CT para pacientes com CPCP resultou em benefício clínico incremental comparado à tomografia e/ou cintilografia para diagnóstico correto de metástase, com maior efetividade e maior custo, sendo observada uma razão de custo-efetividade incremental de R$ 6.015 para a comparação de PET-CT e tomografia computadorizada, R$ 9.107 quando PET-CT foi comparada à cintilografia óssea, e R$ 6.053 para PET-CT em comparação com tomografia + cintilografia para cada diagnóstico correto adicional. As análises de sensibilidade probabilística apresentaram pouca variação, sendo que apenas para a comparação de PET-CT e cintilografia, observou-se um leve potencial de menor efetividade e maior custo. ANÁLISE DE IMPACTO ORÇAMENTÁRIO: Como resultado da projeção observou-se um incremento de custo acumulado em cinco anos de R$31.371.476, considerando um cenário com aumento da difusão de 20% ao ano. Ao considerar um cenário com taxa de difusão com aumento de 10% ao ano do PET-CT, observa-se um incremento de custo acumulado de R$15.685.738 em cinco anos da análise. Além disso, na análise de sensibilidade determinística não foram observadas alterações críticas no custo acumulado em cinco anos. RECOMENDAÇÕES DE AGÊNCIAS INTERNACIONAIS DE ATS: NICE e CADTH recomendam PET-CT para o estadiamento de câncer de pulmão. NICE indica PET-CT para todos os pacientes com câncer de pulmão que poderiam ter tratamento com intenção curativa, bem como pacientes com suspeita de câncer de pulmão que apresentam linfonodos intratorácicos aumentados e para a confirmação de metástases distantes isoladas em pessoas que estão sendo consideradas para tratamento com intenção curativa. O CADTH não especifica a indicação. MONITORAMENTO DO HORIZONTE TECNOLÓGICO: As pesquisas nas bases de dados não identificaram tecnologias novas para o estadiamento de câncer de pulmão de pequenas células. PERSPECTIVA DO PACIENTE: Sobre este tópico não foi aberta chamada pública por ser um procedimento de diagnóstico. CONSIDERAÇÕES FINAIS: Não foi possível avaliar a acurácia do PET-CT em relação aos testes de imagens disponíveis no SUS para estadiar o CPCP, tendo em vista o contexto de teste de referência imperfeito. Assim, a mudança de estádio foi considerada como desfecho clínico de interesse neste parecer. Os estudos sugerem impacto clínico favorável do PETCT no estadiamento de pacientes com CPCP, uma vez que esse método pode alterar o estádio de alguns pacientes, bem como o estádio binário do CPCP (de doença localizada para doença extensa), podendo levar a uma mudança na gestão terapêutica. No entanto, a atual evidência é muito incerta, uma vez que foi oriunda de pequenos estudos com consideráveis limitações metodológicas. Na análise de custo-efetividade demonstrou-se que a PET-CT é custo-efetiva quando comparada à tomografia e/ou cintilografia, considerando um limiar de disposição a pagar de R$40.000 por resultado verdadeiro para detecção de metástase. Na análise de impacto orçamentário projetou-se um incremento de custo acumulado em cinco anos de R$31.371.476, considerando um cenário com aumento da difusão de 20% ao ano e R$15.685.738 com taxa de difusão com aumento de 10% ao ano do PET-CT. Como PET-CT já é ofertada pelo SUS para outras indicações, os centros que já possuem a PET-CT estariam aptos a ofertá-la. RECOMENDAÇÃO PRELIMINAR DA CONITEC: Os membros do Comitê de Produtos e Procedimentos, presentes na 119ª Reunião Ordinária da Conitec realizada no dia 1º de junho de 2023, deliberaram por maioria simples que a matéria fosse disponibilizada em consulta pública com recomendação preliminar desfavorável à ampliação do uso de PETCT para o estadiamento de pacientes com câncer de pulmão de células pequenas. O Comitê considerou que as evidências não são suficientes para a tomada de decisão e endereçaram a realização de subanálises para a população com CPCP potencialmente cirúrgica, com possibilidade de alteração da recomendação no retorno de consulta pública. CONSULTA PÚBLICA: Foram recebidas cinco contribuições, sendo uma técnico-científica e quatro sobre experiência ou opinião. Todas as contribuições foram favoráveis à incorporação de PET-CT para câncer de pulmão de células pequenas. A contribuição técnico-científica reiterou sobre a relevância do procedimento para reduzir procedimentos invasivos, sem citação de referência; e reiterou sobre o procedimento ser recomendado pelo NICE para câncer de pulmão de células pequenas e não pequenas. Dentre as quatro contribuições de experiência e opinião recebidas foram destacados como argumentos o direito à saúde, o direito a um tratamento extra, a relevância de PETCT para o diagnóstico precoce do câncer de pulmão; e a relevância de PET-CT para o estadiamento, monitoramento e otimização da escolha terapêutica. Foram realizadas análises complementares para avaliar o impacto orçamentário de uma possível ampliação do uso de PET-CT para o estadiamento de CPCP em pacientes com potencial cirúrgico, sendo observado um incremento de custo acumulado em cinco anos de R$1.568.574, considerando um cenário com aumento da difusão de 20% ao ano e com um aumento de 10% de difusão ao ano, observa-se um incremento de custo acumulado de R$784.287 em cinco anos da análise. RECOMENDAÇÃO FINAL DA CONITEC: Os membros do Comitê de Produtos e Procedimentos, presentes na 123ª Reunião Ordinária da Conitec realizada no dia 05 de outubro de 2023, deliberaram, por unanimidade, recomendar a ampliação do uso de PET-CT para o estadiamento de pacientes com câncer de pulmão de células pequenas, conforme Protocolo Clínico do Ministério da Saúde. Por fim, foi assinado o Registro de Deliberação Nº 855 / 2023. DECISÃO: ampliar o uso, no âmbito do Sistema Único de Saúde - SUS, da tomografia computadorizada por emissão de pósitrons para pacientes com câncer de pulmão de células pequenas, publicada no Diário Oficial da União, nº 222, Seção 1, página 89, em 23 de novembro de 2023.

PET/CT background noise and its effect on speech recognition.

Positron emission tomography (PET) has been successfully used to investigate central nervous processes, including the central auditory pathway. Unlike early water-cooled PET-scanners, novel PET/CT scanners employ air cooling and include a CT system, both of which result in higher background noise levels. In the present study, we describe the background noise generated by two state-of-the-art air-cooled PET/CT scanners. We measured speech recognition in background noise: recorded PET noise and a speech-shaped noise applied in clinical routine to subjects with normal hearing. Background noise produced by air-cooled PET/CT is considerable: 75.1 dB SPL (64.5 dB(A)) for the Philips Gemini TF64 and 76.9 dB SPL (68.4 dB(A)) for the Philips Vereos PET/CT (Philips Healthcare, The Netherlands). Subjects with normal hearing exhibited better speech recognition in recorded PET background noise compared with clinically applied speech-shaped noise. Speech recognition in both background noises correlated significantly. Background noise generated by PET/CT scanners should be considered when PET is used for the investigation of the central auditory pathway. Speech in PET noise is better than in speech-shaped noise because of the minor masking effect of the background noise of the PET/CT.

Assessment of the viability and treatment response of bone metastases in patients with metastatic castration-resistant prostate cancer using choline PET/CT.

ABSTRACT: This study aimed to evaluate the clinical use of choline-PET/CT for discriminating viable progressive osteoblastic bone metastasis from benign osteoblastic change induced by the treatment effect and evaluating the response of bone metastasis to treatment in metastatic castration-resistant prostate cancer (mCRPC) patients. Thirty patients with mCRPC underwent a total of 56 11C-choline-PET/CT scans for restaging, because 4 patients received 1 scan and 26 had 2 scans. Using 2 (pre- and post-treatment) 11C-choline-PET/CT examinations per patient, treatment response was assessed according to European Organization for Research and Treatment of Cancer (EORTC) criteria in 20 situations, in which only bony metastases were observed on 11C-choline-PET/CT scans. Viable bone metastases and osteoblastic change induced by the treatment effect were identified in 53 (94.6%) and 29 (51.8%) of 56 11C-choline-PET/CT scans, respectively. In 27 cases (48.2%), 11C-choline-PET/CT scans could discriminate the 2 entities. The mean SUVmax of the metastatic bony lesions was 5.82 ±â€Š3.21, 5.95 ±â€Š3.96, 6.73 ±â€Š5.04, and 7.91 ±â€Š3.25 for the osteoblastic, osteolytic, mixed, and invisible types, respectively. Of the 20 situations analyzed, CMR, PMR, SMD, and PMD, as determined by the EORTC, were seen in 1, 2, 3, and 14 cases, respectively. Of the 13 patients with increasing PSA trend, all 13 showed PMD. Of the 2 patients with PSA response of <50%, both 2 showed SMD. Of the 5 patients with PSA response of ≥50%, 1 showed CMR, 2 showed PMR, 1 showed SMD, and 1 showed PMD. Choline-PET/CT is very useful to discriminate viable progressive osteoblastic bone metastasis from osteoblastic change, and assess treatment response of bone metastases in mCRPC.

Nuclear Medicine Imaging Procedures in Oncology.

Nuclear medicine radionuclide imaging is a quantitative imaging modality based on radioisotope-labeled tracers which emit radiation in the form of photons used for image reconstruction. Single photon emission computed tomography (SPECT) and positron emission tomography (PET) are the two noninvasive tomographic three-dimensional radionuclide imaging procedures for both clinical and preclinical settings. In this review on nuclear medicine imaging procedures in oncology, a variety of standard SPECT and PET tracers including radioiodine, 18Fluorine fluorodeoxyglucose (18F-FDG), and 68Gallium-labeled small proteins like Prostate Specific Membrane Antigen (PSMA) or somatostatin analogues and their application as targeted molecular imaging probes for improved tumor diagnosis and tumor phenotype characterization are described. Absolute and semiquantitative approaches for calculation of tracer uptake in tumors during the course of disease and during treatment allow further insight into tumor biology, and the combination of SPECT and PET with anatomical imaging procedures like computed tomography (CT) or magnetic resonance imaging (MRI) by hybrid SPECT/CT, PET/CT, and PET/MRI scanners provides both anatomical information and tumor functional characterization within one imaging session. With the recent establishment of novel molecular radiolabeled probes for specific tumor diagnosis, prognosis, and treatment monitoring, nuclear medicine has been able to establish itself as a distinct imaging modality with increased sensitivity and specificity.

Evaluation of qualitative and quantitative data of Y-90 imaging in SPECT/CT and PET/CT phantom studies.

INTRODUCTION: We aimed to assess the feasibility of SPECT and PET Y-90 imaging, and to compare these modalities by visualizing hot and cold foci in phantoms for varying isotope concentrations. MATERIALS AND METHODS: The data was acquired from the Jaszczak and NEMA phantoms. In the Jaszczak phantom Y-90 concentrations of 0.1 MBq/ml and 0.2 MBq/ml were used, while higher concentrations, up to 1.0 MBq/ml, were simulated by acquisition time extension with respect to the standard clinical protocol of 30 sec/projection for SPECT and 30 min/bed position for PET imaging. For NEMA phantom, the hot foci had concentrations of about 4 MB/ml and the background 0.1 or 0.0 MBq/ml. All of the acquired data was analysed both qualitatively and quantitatively. Qualitative assessment was conducted by six observers asked to identify the number of visible cold or hot foci. Inter-observer agreement was assessed. Quantitative analysis included calculations of contrast and contrast-to-noise ratio (CNR), and comparisons with the qualitative results. RESULTS: For SPECT data up to two cold foci were discernible, while for PET four foci were visible. We have shown that CNR (with Rose criterion) is a good measure of foci visibility for both modalities. We also found good concordance of qualitative results for the Jaszczak phantom studies between the observers (corresponding Krippendorf's alpha coefficients of 0.76 to 0.84). In the NEMA phantom without background activity all foci were visible in SPECT/CT images. With isotope in the background, 5 of 6 spheres were discernible (CNR of 3.0 for the smallest foci). For PET studies all hot spheres were visible, regardless of the background activity. CONCLUSIONS: PET Y-90 imaging provided better results than Bremsstrahlung based SPECT imaging. This indicates that PET/CT might become the method of choice in Y-90 post radioembolization imaging for visualisation of both necrotic and hot lesions in the liver.

Evaluation of 18F-FDG PET/CT images acquired with a reduced scan time duration in lymphoma patients using the digital biograph vision.

BACKGROUND: The superior accuracy and sensitivity of 18F-FDG-PET/CT in comparison to morphological imaging alone leads to an upstaging in up to 30% of lymphoma patients. Novel digital PET/CT scanners might enable to reduce administered tracer activity or scan time duration while maintaining diagnostic performance; this might allow for a higher patient throughput or a reduced radiation exposure, respectively. In particular, the radiation exposure reduction is of interest due to the often young age and high remission rate of lymphoma patients. METHODS: Twenty patients with (suspected) lymphoma (6 for initial staging, 12 after systemic treatment, 2 in suspicion of recurrence) sequentially underwent 18F-FDG-PET/CT examinations on a digital PET/CT (Siemens Biograph Vision) with a total scan time duration of 15 min (reference acquisition protocol) and 5 min (reduced acquisition protocol) using continuous-bed-motion. Both data sets were reconstructed using either standalone time of flight (TOF) or in combination with point spread function (PSF), each with 2 and 4 iterations. Lesion detectability by blinded assessment (separately for supra- and infradiaphragmal nodal lesions and for extranodal lesions), lesion image quantification, and image noise were used as metrics to assess diagnostic performance. Additionally, Deauville Score was compared for all patients after systemic treatment. RESULTS: All defined regions were correctly classified in the images acquired with reduced emission time, and therefore, no changes in staging were observed. Lesion quantification was acceptable, that is, mean absolute percentage deviation of maximum and peak standardized uptake values were 6.8 and 6.4% (derived from 30 lesions). A threefold reduction of scan time duration led to an increase in image noise from 7.1 to 11.0% (images reconstructed with 4 iterations) and from 4.7 to 7.2% (images reconstructed with 2 iterations). No deviations in Deauville Score were observed. CONCLUSION: These results suggest that scan time duration or administered tracer activity can be reduced threefold without compromising diagnostic performance. Especially a reduction of administered activity might allow for a lower radiation exposure and better health economics. Larger trials are warranted to confirm our results.

Performance Evaluation of the uEXPLORER Total-Body PET/CT Scanner Based on NEMA NU 2-2018 with Additional Tests to Characterize PET Scanners with a Long Axial Field of View.

The world's first total-body PET scanner with an axial field of view (AFOV) of 194 cm is now in clinical and research use at our institution. The uEXPLORER PET/CT system is the first commercially available total-body PET scanner. Here we present a detailed physical characterization of this scanner based on National Electrical Manufacturers Association (NEMA) NU 2-2018 along with a new set of measurements devised to appropriately characterize the total-body AFOV. Methods: Sensitivity, count-rate performance, time-of-flight resolution, spatial resolution, and image quality were evaluated following the NEMA NU 2-2018 protocol. Additional measurements of sensitivity and count-rate capabilities more representative of total-body imaging were performed using extended-geometry phantoms based on the world-average human height (∼165 cm). Lastly, image quality throughout the long AFOV was assessed with the NEMA image quality (IQ) phantom imaged at 5 axial positions and over a range of expected total-body PET imaging conditions (low dose, delayed imaging, short scan duration). Results: Our performance evaluation demonstrated that the scanner provides a very high sensitivity of 174 kcps/MBq, a count-rate performance with a peak noise-equivalent count rate of approximately 2 Mcps for total-body imaging, and good spatial resolution capabilities for human imaging (≤3.0 mm in full width at half maximum near the center of the AFOV). Excellent IQ, excellent contrast recovery, and low noise properties were illustrated across the AFOV in both NEMA IQ phantom evaluations and human imaging examples. Conclusion: In addition to standard NEMA NU 2-2018 characterization, a new set of measurements based on extending NEMA NU 2-2018 phantoms and experiments was devised to characterize the physical performance of the first total-body PET system. The rationale for these extended measurements was evident from differences in sensitivity, count-rate-activity relationships, and noise-equivalent count-rate limits imposed by differences in dead time and randoms fraction between the NEMA NU 2 70-cm phantoms and the more representative total-body imaging phantoms. Overall, the uEXPLORER PET system provides ultra-high sensitivity that supports excellent spatial resolution and IQ throughout the field of view in both phantom and human imaging.

The quantification of PET-CT radiotracers to determine minimal scan time using quadratic formulation.

OBJECTIVE: 18F is the most extensively used radioisotope in current clinical practices of PET imaging. This selection is based on the several criteria of pure PET radioisotopes with an optimum half-life, and low positron energy that contributes to a smaller positron range. In addition to 18F, other radioisotopes such as 68Ga and 124I are currently gained much attention with the increase in interest in new PET tracers entering the clinical trials. This study aims to determine the minimal scan time per bed position (Tmin) for the 124I and 68Ga based on the quantitative differences in PET imaging of 68Ga and 124I relative to 18F. METHODS: The European Association of Nuclear Medicine (EANM) procedure guidelines version 2.0 for FDG-PET tumor imaging has adhered for this purpose. A NEMA2012/IEC2008 phantom was filled with tumor to background ratio of 10:1 with the activity concentration of 30 kBq/ml ± 10 and 3 kBq/ml ± 10% for each radioisotope. The phantom was scanned using different acquisition times per bed position (1, 5, 7, 10 and 15 min) to determine the Tmin. The definition of Tmin was performed using an image coefficient of variations (COV) of 15%. RESULTS: Tmin obtained for 18F, 68Ga and 124I were 3.08, 3.24 and 32.93 min, respectively. Quantitative analyses among 18F, 68Ga and 124I images were performed. Signal-to-noise ratio (SNR), contrast recovery coefficients (CRC), and visibility (VH) are the image quality parameters analysed in this study. Generally, 68Ga and 18F gave better image quality as compared to 124I for all the parameters studied. CONCLUSION: We have defined Tmin for 18F, 68Ga and 124I SPECT CT imaging based on NEMA2012/IEC2008 phantom imaging. Despite the long scanning time suggested by Tmin, improvement in the image quality is acquired especially for 124I. In clinical practice, the long acquisition time, nevertheless, may cause patient discomfort and motion artifact.

Impact of image reconstruction method on dose distributions derived from 90Y PET images: phantom and liver radioembolization patient studies.

PET images acquired after liver 90Y radioembolization therapies are typically very noisy, which significantly challenges both visualization and quantification of activity distributions. To improve their noise characteristics, regularized iterative reconstruction algorithms such as block sequential regularized expectation maximization (Q.Clear for GE Healthcare, USA) have been proposed. In this study, we aimed to investigate the effects which different reconstruction algorithms may have on patient images, with reconstruction parameters initially narrowed down using phantom studies. Moreover, we evaluated the impact of these reconstruction methods on voxel-based dose distribution in phantom and patient studies (lesions and healthy livers). The International Electrotechnical Commission (IEC)/NEMA phantom, containing six spheres, was filled with 90Y and imaged using a GE Discovery 690 PET/CT scanner with time-of-flight enabled. The images were reconstructed using Q.Clear (with ß parameter ranging from 0 to 8000) and ordered subsets expectation maximization. The image quality and quantification accuracy were evaluated by computing the hot ([Formula: see text]) and cold ([Formula: see text]) contrast recovery coefficients, background variability (BV) and activity bias. Next, dose distributions and dose volume histograms were generated using MIM® software's SurePlan LiverY90 toolbox. Subsequently, parameters optimized in these phantom studies were applied to five patient datasets. Dose parameters, such as Dmax, Dmean, D70, and V100Gy, were estimated, and their variability for different reconstruction methods was investigated. Based on phantom studies, the ß parameter values optimized for image quality and quantification accuracy were 2500 and 300, respectively. When all investigated reconstructions were applied to patient studies, Dmean, D50, D70, and V100Gy showed coefficients of variation below 8%; whereas the variability of Dmax was up to 30% for both phantom and patient images. Although ß = 300-1000 would provide accurate activity quantification for a region of interest, when considering activity/dose voxelized distribution, higher ß value (e.g. 4000-5000) would provide the greatest accuracy for dose distributions. In this 90Y radioembolization PET/CT study, the ß parameter in regularized iterative (Q.Clear) reconstruction was investigated for image quality, accurate quantification and dose distributions based on phantom experiments and then applied to patient studies. Our results indicate that more accurate dose distribution can be achieved from smoother PET images, reconstructed with larger ß values than those yielding the best activity quantifications but noisy images. Most importantly, these results suggest that quantitative measures, which are commonly used in clinics, such as SUVmax or SUVpeak( equivalent of Dmax), should not be employed for 90Y PET images, since their values would highly depend on the image reconstruction.

Impact of scanner harmonization on PET-based treatment response assessment in metastatic melanoma.

Patients with metastatic melanoma often receive 18F-FDG PET/CT scans on different scanners throughout their monitoring period. In this study, we quantified the impact of scanner harmonization on longitudinal changes in PET standardized uptake values using various harmonization and normalization methods, including an anthropomorphic PET phantom. Twenty metastatic melanoma patients received at least two FDG PET/CT scans, each on two different scanners with an average of 4 months (range: 2-8) between. Scans from a General Electric (GE) Discovery 710 PET CT-1 were harmonized to the GE Discovery VCT using image reconstruction settings matching recovery coefficients in an anthropomorphic phantom with bone equivalent inserts and wall-less synthetic lesions. In patient images, SUVmax was measured for each melanoma lesion and time-point. Lesions were classified as progressing, stable, or responding based on pre-defined threshold of ±30% change in SUVmax. For comparison, harmonization was also performed using simpler methods, including harmonization using a NEMA phantom, post-reconstruction filtering, reference region normalization of SUVmax, and use of SUVpeak instead of SUVmax. In the 20 patients, 90 lesions across two time-points were available for treatment response assessment. Treatment response classification changed in 47% (42/90) of cases after harmonization with anthropomorphic phantom. Before harmonization, 37% (33/90) of the lesions were classified as stable (changing less than 30% between two time-points), while the fraction of stable lesions increased to 58% (52/90) after harmonization. Harmonization with the NEMA phantom agreed with harmonization with the anthropomorphic phantom in 91% (82/90) of cases. Post-reconstruction filtering agreed with anthropomorphic phantom-based harmonization in 83% (75/90) cases. The utilization of reference regions for normalization or SUVpeak was unable to correct for changes as identified by the anthropomorphic phantom-based harmonization. Overall, PET scanner harmonization has a major impact on individual lesion treatment response classification in metastatic melanoma patients. Harmonization using the NEMA phantom yielded similar results to harmonization using anthropomorphic phantom, while the only acceptable post-reconstruction technique was post-reconstruction filtering. Phantom-based harmonization is therefore strongly recommended when comparing lesion uptake across time-points when the images have been acquired on different PET scanners.

Importance of combined use of preoperative 18F-FDG PET/CT imaging and intraoperative 18F-FDG handheld gamma probe detection in recurrent papillary thyroid cancer.

Radio-guided surgery using an intra-operative positron emission tomography (PET) probe in recurrent thyroid cancer (RTC) can be a useful method for tumor localization, verification of complete excision and to decrease operation time. We describe a case of RTC whose serum thyroglobulin (Tg) level was 5.6ng/mL. Preoperative fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) revealed two focal abnormalities in the anterior tracheal and right upper mediastinal regions and a handheld gamma probe was used intraoperatively to identify the hot areas seen on PET scan. Postoperative 18F-FDG PET/CT imaging after tumor excision was normal. This case shows that recurrent tumor can be localized correctly using 18F-FDG PET/CT and a surgical gamma probe.

Evaluating and comparing the image quality and quantification accuracy of SiPM-PET/CT and PMT-PET/CT.

OBJECTIVE: The aim of this study was to evaluate the image quality and the quantification accuracy of Biograph Vision PET/CT scanner as a SiPM-PET in comparison to the conventional PMT-PET, Biograph mCT PET/CT scanner. METHODS: This study consisted of a phantom study and a retrospective clinical analysis where patients underwent 18F-FDG PET/CT in both PET systems. The body phantom of the NEMA IEC with 10-37 mm diameter spheres were filled with an 18F-FDG solution. The root mean square error (RMSE) of SUV, the detectability of 10-mm sphere, NECphantom, the background variability (N10mm) and the contrast-noise-ratio (QH,10 mm/N10mm) were calculated based on the phantom analysis. We also examined the quality of the acquired clinical images using the NECpatient, NECdensity, SNRliver, SUVliver and SUVlesion. RESULTS: In the phantom study on Vision scanner, RMSE was relatively lower when the iteration number was 2, 3 or 4. To satisfy a visual score of 1.5 and the reference range of QH,10 mm/N10mm, a 60-s or longer acquisition was required. Our clinical findings show that NECpatient averaged 17.4 ± 1.72 Mcounts/m in mCT and 29.1 ± 2.83 Mcounts/m in Vision. Furthermore, NECdensity averaged 0.29 ± 0.05 kcounts/cm3 in mCT and 0.53 ± 0.09 kcounts/cm3 in Vision, respectively, whereas SNRliver averaged 14.6 ± 3.77% in mCT and 21.3 ± 1.69% in Vision (P = 0.0156), respectively. Finally, SUVliver averaged 2.82 ± 0.28 and 2.55 ± 0.30, SUVlesion ranged 1.6-17.6 and 1.9-22.9 in mCT and Vision, respectively. CONCLUSION: SiPM-PET/CT provides superior image quality and quantification accuracy compared to PMT-PET/CT.

The impact of time-of-flight, resolution recovery, and noise modelling in reconstruction algorithms in non-solid-state detectors PET/CT scanners: - multi-centric comparison of activity recovery in a 68Ge phantom.

The reconstruction algorithms implemented on PET/CT scanners offer gain in activity recovery of small lesions at an extent that is not full known yet. METHODS: A cylindrical phantom with warm background and hot spheres filled with a 68Ge epoxy was acquired with four non-state-solid-detectors PET/CT scanners: mCT, Ingenuity TF, Discovery 710, and IQ. Images were reconstructed switching on and off time-of-flight (TOF), point spread function (PSF) modelling, and Bayesian penalised likelihood (BPL). Images were reconstructed with the default parameters recommended by the manufacturers. The recovery coefficient (RCmax), defined as the ratio of the measured maximum activity concentration in each sphere and the actual one, and the coefficient of variation (CoVBAC) defined as the ratio of the standard deviation and the average of background activity concentration were measured. RESULTS: While with IR alone, complete recovery of the activity concentration is achieved down to the 22 mm diameter's sphere, with TOF, TOF + PSF and BPL it is achieved down to the 17 mm diameter one. At smaller dimensions, the difference among the various studied reconstruction algorithms is substantial for the 13- and 17-mm diameters' spheres for all scanners and for all reconstructions with a considerable gain in RCmax when PSF and BPL are used. At 10 mm diameter's sphere the difference among the algorithms is significantly reduced, except for BPL which still guarantees a gain in RCmax.

High detection sensitivity and reliable morphological correlation of PET with a silicon photomultiplier for primary tongue squamous cell carcinoma.

OBJECTIVE: A positron emission tomography (PET) scanner using a silicon photomultiplier (SiPM PET) in place of a photomultiplier tube significantly improves the spatial and time resolution. It may also improve the evaluation of smaller lesions compared to conventional (non-SiPM) PET scanners. We compared the maximum standardized uptake value (SUVmax), detection sensitivity, and morphological correlation using magnetic resonance imaging (MRI) for primary tongue squamous cell carcinoma between the SiPM PET and non-SiPM PET scanner. METHODS: We retrospectively reviewed the F-18 fluorodeoxyglucose (FDG) PET/CT features of tongue squamous cell carcinomas in consecutive, newly diagnosed, and pathologically verified patients. Twenty-five of 46 patients were scanned using SiPM PET scanner and the remaining 21 patients were scanned with a non-SiPM PET scanner. We compared the SUVmax and visual evaluation of primary tumor detectability, and the correlation between the PET-based and MRI-based tumor size (long axis, thickness, and volume). Differences in SUVmax and detection sensitivity for the primary tumor were analyzed using Welch's t test and Fisher's exact test, respectively. Correlations among the PET-based, MRI-based tumor size, and SUVmax were assessed using Spearman's rank correlation coefficient. RESULTS: SUVmax of both T1/T2 and T3/T4 primary tumors were significantly higher for the SiPM PET (T1/T2 mean SUVmax: 6.6 ± 4.3, T3/T4 mean SUVmax: 18.2 ± 9.8) than that for the non-SiPM PET (T1/T2 mean SUVmax: 3.4 ± 1.4, T3/T4 mean SUVmax: 10.2 ± 4.9) (P < 0.05). While all cases of T3/T4 primary tumors were detected by both PET scanners, the detection sensitivity for T1/T2 primary tumors was significantly higher for the SiPM PET (80%) than that for the non-SiPM PET (36.4%) (P < 0.05). MRI-based tumor size correlated significantly with SiPM PET-based tumor long axis (ρ = 0.74) and volume (ρ = 0.91), but not with the non-SiPM PET-based tumor long axis and volume in T1/T2 primary lesions. Correlation between MRI-based tumor size and SUVmax was significant in both PET scanners; however, no significant difference was observed between the two scanners. CONCLUSIONS: The SiPM PET provides better detection sensitivity and a reliable morphological correlation for the T1/T2 primary tongue tumors than the non-SiPM PET due to its high performance.

Detectability of small objects in PET/computed tomography phantom images with Bayesian penalised likelihood reconstruction.

OBJECTIVES: This study investigated the subcentimetre lesion detection gains of a Bayesian penalised likelihood reconstruction (BPLR) (Q.Clear, GE Healthcare, Milwaukee, USA) in PET/computed tomography (CT) phantom images and compares observer performance with ordered subset expectation maximisation (OSEM) reconstruction images (VUE Point HD, GE Healthcare). METHODS: Images were presented to three blinded experienced observers to identify lesions and assign confidence ratings. Responses were analysed using jackknife alternative free receiver operator characteristic (JAFROC) software. Phantom lesions (active and nonactive) were constructed using putty. Seventy nonactive and 93 (F) active lesions, with diameters of 3, 5 or 7 mm were suspended in active backgrounds at varying contrast ratios (2:1-32:1) within an National Electrical Manufacturers Association 2012 phantom. PET/CT images were acquired with a GE Discovery 710 and reconstructed using both BPLR (penalisation coefficient 400) and high-definition attenuation corrected (HDAC) OSEM (2 iterations, 24 subsets). RESULTS: Small but significant (P = 0.009) visual detection gains were seen for active lesions with BPLR [weighted JAFROC figure of merit (wJAFROC FOM) = 0.77] over OSEM (FOM = 0.74). When split by subset, these improvements were significant for 5 mm and lesion to background ratio of 8:1. No significant (P = 0.514) differences were seen for the identification of nonactive lesions of any size (BPLR FOM = 0.74 and OSEM FOM = 0.73). CONCLUSIONS: Significant detection gains were demonstrated for small active lesions with BPLR over OSEM. Coupled with the significant increase in contrast-to-noise ratio, these results support the use of BPLR in the imaging of small active (≤7 mm) lesions but show no improvement with BPLR in the identification of true negative lesions.

Traceable point-like 68Ge/68Ga source with a spherically symmetric positron absorber for PET scanners.

A novel traceable point-like 68Ge/68Ga source was developed for calibration of positron emission tomography (PET) scanners. The source was equipped with a spherically symmetric acrylic positron absorber. The physical characteristics of photons emitted from the point-like source were evaluated by Monte Carlo simulation, considering possible geometrical uncertainties. The calibration factor of a clinical PET/CT scanner was evaluated using four manufactured point-like sources as a practical application of the point-like source. The results were consistent with that determined by the conventional cross-calibration method. The traceable point-like 68Ge/68Ga source is expected to be a simple and practical tool for determining the calibration factor and evaluating the physical characteristics of PET scanners.

Textitis as Seen on 18F-NaF Imaging Using an Ultra-High-Resolution Positron Emission Mammography Scanner.

Textitis is a new term used to refer to the degenerative-strain osteoarthritis that comes from excessive use of a smart phone. 18F-NaF is increasingly used in diagnosing skeletal pain that is not identified on radiographs. We report a case of a 26-y-old woman with left breast cancer referred for 18F-NaF PET/CT, who was complaining of right thumb and wrist pain. Findings were negative for bone secondaries. Dedicated hands views were acquired on a positron emission mammography scanner and showed focal uptake at the first carpometacarpal and second metacarpophalangeal joints. On the basis of the strong history, the findings were likely due to active arthritic changes caused by repetitive strain injury from excessive text messaging.

PET and SPECT imaging of the brain: a review on the current status of nuclear medicine in Japan.

Radiolabeled tracers allow visualization of not only perfusion, but receptors, function, and metabolism as well. Although spatial resolution is lower than that of computed tomography and magnetic resonance imaging, positron emission tomography (PET) and single photon emission computed tomography (SPECT) have great potential for target-specific imaging. In this review, we discuss several SPECT and PET tracers used in brain imaging, specifically focusing on tracers currently available, or developed, in Japan. Several important and sophisticated methods exist for analysis of brain PET and SPECT images. Two of them, quantitative cerebral blood flow measurement and voxel-based statistical analysis are discussed in this review. The former method, which employs acetazolamide loading, is useful for evaluation of the brain perfusion reserve for ischemic brain diseases. The latter is useful in diagnosing dementing diseases. Additionally, great strides have been made in the development of the technology used in the scanners. New SPECT systems based on cadmium-zinc-telluride, PET/MRI, and semiconductor PET/CT may provide higher spatial resolution with an acquisition time shorter than ever before. Such developments of both tracers and scanners can be integrated for unprecedented imagery of the brain, providing valuable insight into underlying causes of some fatal brain disorders.

Subsecond total-body imaging using ultrasensitive positron emission tomography.

A 194-cm-long total-body positron emission tomography/computed tomography (PET/CT) scanner (uEXPLORER), has been constructed to offer a transformative platform for human radiotracer imaging in clinical research and healthcare. Its total-body coverage and exceptional sensitivity provide opportunities for innovative studies of physiology, biochemistry, and pharmacology. The objective of this study is to develop a method to perform ultrahigh (100 ms) temporal resolution dynamic PET imaging by combining advanced dynamic image reconstruction paradigms with the uEXPLORER scanner. We aim to capture the fast dynamics of initial radiotracer distribution, as well as cardiac motion, in the human body. The results show that we can visualize radiotracer transport in the body on timescales of 100 ms and obtain motion-frozen images with superior image quality compared to conventional methods. The proposed method has applications in studying fast tracer dynamics, such as blood flow and the dynamic response to neural modulation, as well as performing real-time motion tracking (e.g., cardiac and respiratory motion, and gross body motion) without any external monitoring device (e.g., electrocardiogram, breathing belt, or optical trackers).