Global collaboration is the cornerstone of scientific advancement. Frontiers in Medicine has organized a series of special edition Research Topics, with the goal of highlighting the latest advancements in Nuclear Medicine across the globe, showcasing the academic excellence and high-quality work of internationally recognized researchers. These collections aim to shed light on the recent progress made across the entire breadth of the Nuclear Medicine field, and reflect on the future challenges faced by researchers across borders.

Seoul National University Hospital

Dong-a University Hospital

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Frontiers in Medicine

Nuclear Medicine

Global Excellence in Nuclear Medicine: Asia and Australasia

The aim of this study was to retrospectively analyze 18F-fluorodeoxyglucose (18F-FDG) PET/CT images of non-infected hip arthroplasty patients and summarize findings that may be useful for clinical practice. 18F-FDG PET/CT images of non-infected hip arthroplasty patients were collected from September 2009 to August 2021. The region of interest was independently delineated by 2 physicians and maximum standardized uptake values (SUVmax) were recorded and compared. Serologic data were also collected and the correlation between SUVmax and serologic parameters was analyzed, while the images were classified based on the 18F-FDG uptake pattern in the images using the diagnostic criteria proposed by Reinartz et al. The interval between hip replacement and PET/CT was classified by year and the characteristics of the 2 groups were compared. The images of patients who underwent PET/CT multiple times were analyzed dynamically. A total of 121 examinations were included; 6 patients underwent PET/CT twice and 2 patients had 3 scans. There were no significant correlations between SUVmax and serologic results. The interobserver agreement between the 2 physicians in the classification according to the criteria of Reinartz et al. was 0.957 (P<0.005). Although there was nonspecific uptake in cases with an arthroplasty-to-PET/CT interval <1 year, this was nonsignificant. Additionally, 18F-FDG showed potential utility for dynamic observation of the condition of the hip. SUVmax provided information independent of serologic results, meanwhile18F-FDG showed potential applicability to the dynamic monitoring of hip arthroplasty-related diseases. However, the presence of blood vessels and muscles affected image interpretation and the specificity of 18F-FDG was not optimal. A more specific radionuclide is needed to maximize the benefits of using PET/CT for the assessment of periprosthetic joint infection (PJI).

Purpose: The aim of this study was to retrospectively analyze 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/ computed tomography (CT) images of non-infected hip arthroplasty patients and summarize findings that may be useful for clinical practice.Methods: 18F-FDG PET/CT images of non-infected hip arthroplasty patients were collected from September 2009 to August 2021. The region of interest was independently delineated by two physicians and maximum standardized uptake values (SUVmax) were recorded and compared. Serologic data were also collected and the correlation between SUVmax and serologic parameters was analyzed, while the images were classified based on the 18F-FDG uptake pattern in the images using the diagnostic criteria proposed by Reinartz et al. (<a href="#B9">9</a>). The interval between hip replacement and PET/CT was classified by year and the characteristics of the two groups were compared. The images of patients who underwent PET/CT multiple times were analyzed dynamically.Results: A total of 121 examinations were included; six patients underwent PET/CT twice and two patients had three scans. There were no significant correlations between SUVmax and serologic results. The interobserver agreement between the two physicians in the classification according to the criteria of Reinartz et al. (<a href="#B9">9</a>) was 0.957 (P &lt; 0.005). Although there was non-specific uptake in cases with an arthroplasty-to-PET/CT interval this was non-significant. Additionally, 18F-FDG showed potential utility for dynamic observation of the condition of the hip.Conclusion: SUVmax provided information independent of serologic results, meanwhile 18F-FDG showed potential applicability to the dynamic monitoring of hip arthroplasty-related diseases. However, the presence of blood vessels and muscles affected image interpretation and the specificity of 18F-FDG was not optimal. A more specific radionuclide is needed to maximize the benefits of using PET/CT for the assessment of periprosthetic joint infection (PJI).

Performance characteristics of 18F–fluorodeoxyglucose in non-infected hip replacement

Primary pulmonary nucleoprotein of the testis (NUT) carcinoma is very rare in clinic. In this study, the clinicopathological manifestations and imaging features of the primary pulmonary NUT carcinoma were investigated to improve the diagnosis of this disease.  6 patients with pathologically diagnosed pulmonary NUT carcinoma were analyzed, Most of the patients with pulmonary NUT carcinomas presented as heterogeneous lobulated masses, four cases were located in the upper lobe of the left lung, one case in the middle lobe of the right lung, and one case in the lower lobe of the right lung, with the maximum diameter ranging from 1.30 to 8.90 cm and the median of 3.55 cm, most of them were irregularly shaped, with more lobulated margins and more heterogeneous density (83.33%), and the enhancement was mild. PET/CT showed increased 18F-FDG uptake in the lesion and metastatic areas and the maximum standardized uptake value (SUVmax) ranged from 5 to 40. Mediastinal lymph node metastasis was the most common while bone metastasis, liver metastasis, and brain metastasis occured as well. In patients with central lung masses, rapid disease progression, and poor response to initial treatment, the possibility of NUT cancer should be considered and anti-NUT monoclonal antibody immunohistochemical staining, combined with genetic detection, if necessary, should be performed as soon as possible. CT and PET/CT imaging are essential for the staging, management, treatment response assessment, and monitoring of pulmonary NUT cancer.

Objective: Primary pulmonary nucleoprotein of the testis (NUT) carcinoma is very rare in the clinic. In this study, the clinicopathological manifestations and imaging features of the primary pulmonary NUT carcinoma were investigated to improve the diagnosis of this disease.Methods: Six patients with pathologically diagnosed pulmonary NUT carcinoma were analyzed, including three males and three females, aged 19–64 (49.00 ± 16.40) years, with clinical manifestations of cough in two cases, hoarseness in one case, blood in sputum in one case, chest pain in one case, and physical examination findings in one case, with a disease duration of 5 days to 4 months. The clinical and imaging data including CT and PET/CT were retrospectively analyzed. Further literature reviews were analyzed in both pulmonary and extrapulmonary NUT carcinoma cases who performed 18F-FDG PET/CT.Results: Most of the patients with pulmonary NUT carcinomas presented as heterogeneous lobulated masses (83.33%), four cases (66.67%) were located in the upper lobe of the left lung, one case (16.67%) in the middle lobe of the right lung, and one case (16.67%) in the lower lobe of the right lung, with the maximum diameter ranging from 1.30 to 8.90 cm and the median of 3.55 cm, most of them were irregularly shaped, with more lobulated margins and more heterogeneous density (83.33%), and the enhancement was mild. PET/CT showed increased 18F-FDG uptake in the lesion and metastatic areas. Both the pulmonary NUT patients in this study and literature reviews showed the SUVmax of the tumor ranged from 5 to 40 with an average value of 12.8, whereas that of extrapulmonary lesions had a range of SUVmax at 4.5–64.1 and a mean of 13.8.Conclusion: In patients with central lung masses, rapid disease progression, and poor response to initial treatment, the possibility of NUT cancer should be considered and anti-NUT monoclonal antibody immunohistochemical staining, combined with genetic detection, if necessary, should be performed as soon as possible. CT and PET/CT imaging are essential for the staging, management, treatment response assessment, and monitoring of pulmonary NUT cancer.

Clinical imaging of primary pulmonary nucleoprotein of the testis carcinoma

Purpose: To determine whether stacked deep learning models based on PET/CT images and clinical data can help to predict epidermal growth factor receptor (EGFR) mutations in lung cancer. Methods: We analyzed data from two public datasets of patients who underwent 18F-FDG PET/CT. Three PET deep learning ResNet models and one CT deep learning ResNet model were trained as low-level predictors based on PET and CT images, respectively. A high-level Support Vector Machine model (Stack PET/CT & Clinical model) was trained using the prediction results of the low-level predictors and clinical data. The clinical data included sex, age, smoking history, SUVmax and SUVmean of the lesion. Fivefold cross-validation was used in this study to validate the prediction performance of the models. The predictive performance of the models was evaluated by receiver operator characteristic (ROC) curves. The area under the curve (AUC) was calculated. Results: One hundred forty-seven patients were included in this study. Among them, 37/147 cases were EGFR mutations, and 110/147 cases were EGFR wild-type. The ROC analysis showed that the Stack PET/CT & Clinical model had the best performance (AUC=0.85±0.09), with 0.76, 0.85 and 0.83 in sensitivity, specificity and accuracy, respectively. Three ResNet PET models had relatively higher AUCs (0.82±0.07, 0.80±0.08 and 0.79±0.07) and outperformed the CT model (AUC = 0.58±0.12). Conclusion: Using stack generalization, the deep learning model was able to efficiently combine the anatomic and biological imaging information gathered from PET/CT images with clinical data. This stacked deep learning model showed a strong ability to predict EGFR mutations with high accuracy.

Purpose: To determine whether stacked deep learning models based on PET/CT images and clinical data can help to predict epidermal growth factor receptor (EGFR) mutations in lung cancer.Methods: We analyzed data from two public datasets of patients who underwent 18F-FDG PET/CT. Three PET deep learning ResNet models and one CT deep learning ResNet model were trained as low-level predictors based on PET and CT images, respectively. A high-level Support Vector Machine model (Stack PET/CT and Clinical model) was trained using the prediction results of the low-level predictors and clinical data. The clinical data included sex, age, smoking history, SUVmax and SUVmean of the lesion. Fivefold cross-validation was used in this study to validate the prediction performance of the models. The predictive performance of the models was evaluated by receiver operator characteristic (ROC) curves. The area under the curve (AUC) was calculated.Results: One hundred forty-seven patients were included in this study. Among them, 37/147 cases were EGFR mutations, and 110/147 cases were EGFR wild-type. The ROC analysis showed that the Stack PET/CT &amp; Clinical model had the best performance (AUC = 0.85 ± 0.09), with 0.76, 0.85 and 0.83 in sensitivity, specificity and accuracy, respectively. Three ResNet PET models had relatively higher AUCs (0.82 ± 0.07, 0.80 ± 0.08 and 0.79 ± 0.07) and outperformed the CT model (AUC = 0.58 ± 0.12).Conclusion: Using stack generalization, the deep learning model was able to efficiently combine the anatomic and biological imaging information gathered from PET/CT images with clinical data. This stacked deep learning model showed a strong ability to predict EGFR mutations with high accuracy.

Using stacked deep learning models based on PET/CT images and clinical data to predict EGFR mutations in lung cancer

Purpose: Primary thymic extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) lymphoma is a rare type of MALT lymphoma. We aim to investigate the clinicopathologic features, 18F-FDG PET/CT findings and outcome for patients with primary thymic MALT lymphoma; to explore the correlation between metabolic parameters and immunohistochemical phenotypes. Methods: A retrospective single-center study enrolled 12 patients with primary thymic MALT lymphoma between 2010 and 2021. A total of 19 18F-FDG PET/CT scans were performed, and clinicopathologic and immunohistochemical characteristics, PET/CT imaging features, and outcomes were analyzed. Results: The male-to-female ratio was 1. The median age at diagnosis was 40 (range 31–68). The long diameter of the lesions ranges from 3.5 to 15.7. Histopathological examinations revealed the normal thymic lobular architecture is effaced by a diffuse lymphoid infiltrate, but residual Hassall corpuscles can still be identified, mostly with CD20+, PAX5+, CD3-, CD23-, CD10-, BCL-6- , cyclin D1-, EBER- and low Ki-67. The gene rearrangement indicated that IGH gene but not TCR gene found in 7 patients. At six initial PET/CT scans, mean SUVmax = 6.8 (range, 3.1–12.4), mean MTV = 40.0 (range, 6.7–81.4), mean TLG = 144.3 (range, 19.7–286.4). During the follow-up period, there was no death except for the patient with DLBCL who died 59 months after diagnosis of primary thymic MALT. No significant correlation between SUVmax and Ki-67 index was observed (r = 0.355, P > 0.05) . Conclusion: Primary thymic MALT lymphoma should be considered in patients with multilocular cystic lesions with different degrees of 18F-FDG uptake in the anterior mediastinum. The results of this study showed no correlation between SUVmax and KI-67 index.

Purpose: Primary thymic extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) lymphoma is a rare type of MALT lymphoma. We aim to investigate the clinicopathologic features, 18F-FDG PET/CT findings and outcomes for patients with primary thymic MALT lymphoma; to explore the correlation between metabolic parameters and immunohistochemical phenotypes.Methods: A retrospective single-center study enrolled 12 patients with primary thymic MALT lymphoma between 2010 and 2021. Nineteen 18F-FDG PET/CT scans were performed, and clinicopathologic and immunohistochemical characteristics, PET/CT imaging features, and outcomes were analyzed.Results: The male-to-female ratio was 1. The median age at diagnosis was 40 (range 31–68). The long diameter of the lesions ranged from 3.5 to 15.7. Histopathological examinations revealed that the normal thymic lobular architecture was effaced by a diffuse lymphoid infiltrate, but residual Hassall corpuscles could still be identified, mostly with CD20+, PAX5+, CD3-, CD23-, CD10-, BCL-6-, cyclin D1-, EBER- and low Ki-67. The gene rearrangement indicated that the IGH gene but not TCR gene was found in 7 patients. Six initial PET/CT scans showed a mean SUVmax of 6.8 (range, 3.1–12.4), a mean MTV = 40.0 (range, 6.7–81.4), and a mean TLG = 144.3 (range, 19.7–286.4). During the follow-up period, there was no death except for the patient with DLBCL who died 59 months after diagnosis of primary thymic MALT. No significant correlation between SUVmax and Ki-67 index was observed (r = 0.355, P &gt; 0.05).Conclusion: Primary thymic MALT lymphoma should be considered in patients with multilocular cystic lesions with different degrees of 18F-FDG uptake in the anterior mediastinum. The results of this study showed no correlation between SUVmax and Ki-67 index.

Thymic Extranodal Marginal-Zone Lymphoma of Mucosa-Associated Lymphoid Tissue: Pathological Features, 18F-FDG PET/CT Findings and Prognosis in 12 Cases

OBJECTIVE: To evaluate the association between radiation exposure from repeated nuclear medicine (NM) examinations and the subsequent risk of neoplasm in pediatric patients. METHODS: From 2000 to 2017, participants under 18 years of age who underwent NM scanning were identified using the Health and Welfare Data Science Center (HWDC) dataset, which was extracted from the Taiwan National Health Insurance Research Database (NHIRD). Both the exposed cohort and unexposed subjects were followed up with until the presence of any malignancy arose, including malignant brain, lymphoid and hematopoietic tumors and benign brain or other central nervous tumors. RESULTS: There were 35,292 patients in the exposed cohort and 141,152 matched subjects in the nonexposed group. The exposed cohort had an overall higher IR (IR: incidence rate, per 100 000 person-years) of any malignancy and benign central nervous tumor than the nonexposed group (IR, 16.9 vs. 1.54; adjusted hazard ratio [HR], 10.9; 95% CI, 6.53–18.2). Further stratifying the number of NM examinations into 1-2, 3-4, and 5 or more times revealed that the IR of pediatric neoplasms increased gradually with the increased frequency of NM examinations (IR, 11.5; adjusted HR, 7.5; 95% CI, 4.29–13.1; IR, 25.8; adjusted HR, 15.9; 95% CI, 7.00–36.1; IR, 93.8; adjusted HR, 56.4; 95% CI, 28.8–110.3). CONCLUSION: NM examination is significantly associated with a higher risk of pediatric neoplasms, according to our population-based data. Thorough radiation protection and dose reduction in pediatric NM procedures should be an issue of concern.

Objective: To evaluate the association between radiation exposure from repeated nuclear medicine (NM) examinations and the subsequent risk of neoplasm in pediatric patients.Methods: From 2000 to 2017, participants under 18 years of age who underwent NM scanning were identified using the Health and Welfare Data Science Center (HWDC) dataset, which was extracted from the Taiwan National Health Insurance Research Database (NHIRD). Both the exposed cohort and unexposed subjects were followed up with until the presence of any malignancy arose, including malignant brain, lymphoid and hematopoietic tumors and benign brain or other central nervous tumors.Results: There were 35,292 patients in the exposed cohort and 141,152 matched subjects in the non-exposed group. The exposed cohort had an overall higher IR (IR: incidence rate, per 100,000 person-years) of any malignancy and benign central nervous tumor than the non-exposed group [IR, 16.9 vs. 1.54; adjusted hazard ratio (HR), 10.9; 95% CI, 6.53–18.2]. Further stratifying the number of NM examinations into 1-2, 3-4, and 5 or more times revealed that the IR of pediatric neoplasms increased gradually with the increased frequency of NM examinations (IR, 11.5; adjusted HR, 7.5; 95% CI, 4.29–13.1; IR, 25.8; adjusted HR, 15.9; 95% CI, 7.00–36.1; IR, 93.8; adjusted HR, 56.4; 95% CI, 28.8–110.3).Conclusion: NM examination is significantly associated with a higher risk of pediatric neoplasms, according to our population-based data. Thorough radiation protection and dose reduction in pediatric NM procedures should be an issue of concern.