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Abstract Purposes To explore the clinical feasibility and efficacy of a deep inspiration breath-hold (BH) PET/CT using [18F]AlF-NOTA-LM3 on upper abdominal lesions in patients with neuroendocrine tumors (NETs). Methods Twenty-three patients underwent a free-breath (FB) whole-body PET/CT, including a 10 min/bed scan for the upper abdomen with a vital signal monitoring for respiratory gating (RG) followed by a 20-second BH PET/CT covering the same axial range. For the upper abdomen bed, the following PET series was reconstructed: a 2-min FB PET; RG PET (6 bins); a 20-second and 15-second BH PET (BH_15 and BH_20). Semi-quantitative analysis was performed to compare liver SUVmean, lesion SUVmax, MTV, its percentage difference and target-to-background ratio (TBR) between both BH PET and RG PET images. Subgroup analysis considered lesion location, MTV and SUVmax. A 5-point Likert scale was used to perform visual analysis and any missed or additional lesions were identified compared with RG PET. Results Quantitative analysis on overall lesions (n = 78) revealed higher SUVmax and TBR, and smaller MTV for both BH PET compared to FB and RG PET, with lesion location-specific variations. Neither significant difference was observed in all metrics between RG and FB PET in larger lesions, nor in MTV in lower-uptake lesions. However, both BH PET significantly enhanced these measurements. In the visual analysis, both BH PET showed noninferior performance to RG PET, and were evaluated clinically acceptable. Additional and missed lesions were observed in FB and both BH PET compared with RG PET, but didn’t alter the clinical management. The BH_15 PET showed comparable performance to BH_20 PET in any comparison. Conclusion The BH PET/CT using [18F]AlF-NOTA-LM3 is effective in detecting upper abdominal lesions, offering more accurate quantitative measurements. Using a novel PET/CT scanner, a 15-second BH PET can provide comparable and superior performance to RG PET, indicating potential feasibility in clinical routines.

The World Health Organization (WHO) 2017 classifications for neuroendocrine neoplasms (NENs) subdivided grade 3 pancreatic neuroendocrine neoplasms (pNENs) into G3 well-differentiated pancreatic neuroendocrine tumors (G3 pNETs) and poorly differentiated pancreatic neuroendocrine carcinomas (pNECs), according to the mitotic count, Ki-67 index, and cell differentiation. As a new category, G3 pNETs remain a challenging group of tumors to manage by lacking large randomized trials and consensus to support its clinical practice. Therefore, the Chinese Pancreatic Surgery Association, Chinese Society of Surgery, Chinese Medical Association gathered experts in this field to formulate this consensus for the diagnosis and treatment of G3 pNETs.

[18F]-Florbetazine ([18F]-92) is a selective PET tracer for β-amyloid (Aβ) depositions with a novel diaryl-azine scaffold to reduce lipophilicity and to achieve higher gray-to-white matter contrast. We aimed to assess its diagnostic value in Alzheimer's disease (AD) and pharmacokinetics characteristics in human subjects. Methods: Six healthy controls (HCs) and nine AD patients underwent dynamic PET examination with [18F]-Florbetazine and a structural MRI scan. The time-activity-curves (TACs) for volumes of interest (VOIs) in cerebral cortex, cerebellar cortex and cerebral white matter was depicted and their standardized uptake value ratios (SUVRs) with cerebellar cortex as reference were compared between HCs and AD patients. The cerebral gray-to-white matter SUV ratio (GWR) was also calculated. Results: In HCs, radioactivities in the cerebral cortex VOIs were homogeneously low and at the same level as in cerebellar cortex, while in AD patients, cortical VOIs expected to contain Aβ exhibited high radioactivity. Cerebral cortex SUVRs remain relatively low in HCs while keep increasing along with time in AD patients. After 15 min, the cerebral cortex SUVRs became significant higher in AD patients compared to HCs with 100 % discrimination accuracy. In AD patients, GWR remained over 1.3 for all time intervals and visual inspection showed lower uptake in cerebral white matter compared to cerebral cortex. Conclusion: [18F]-Florbetazine PET showed high uptake on Aβ plaques and high gray-to-white contrast in AD patients that are favorable in visual read. [18F]-Florbetazine can be potentially used for detection and quantification of Aβ depositions in the living human brain.

Abstract Background Microsatellite instability-high (MSI-H) is a unique genomic status in many cancers. However, its role in the genomic features and immunotherapy in cholangiocarcinoma (CCA) is unclear. This study aimed to systematically investigate the genomic characterization and immunotherapy efficacy of MSI-H patients with CCA. Methods We enrolled 887 patients with CCA in this study. Tumor samples were collected for next-generation sequencing. Differences in genomic alterations between the MSI-H and microsatellite stability (MSS) groups were analyzed. We also investigated the survival of PD-1 inhibitor-based immunotherapy between two groups of 139 patients with advanced CCA. Results Differential genetic alterations between the MSI-H and MSS groups included mutations in ARID1A, ACVR2A, TGFBR2, KMT2D, RNF43, and PBRM1 which were enriched in MSI-H groups. Patients with an MSI-H status have a significantly higher tumor mutation burden (TMB) (median 41.7 vs. 3.1 muts/Mb, P

Abstract Background Triple-negative breast cancer (TNBC) is one of the most lethal malignant tumors among women, characterized by high invasiveness, high heterogeneity, and lack of specific therapeutic targets such as estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. Trophoblast cell-surface antigen-2 (TROP-2) is a transmembrane glycoprotein over-expressed in 80% of TNBC patients and is associated with the occurrence, progress, and poor prognosis of TNBC. The TROP-2 targeted immunoPET imaging allows non-invasive quantification of the TROP-2 expression levels of tumors, which could help to screen beneficiaries most likely to respond to SG and predict the response. This study aimed to develop a 89Zr/177Lu-radiolabeled anti-TROP-2 antibody (NY003) for immunoPET and SPECT imaging, as well as radioimmunotherapy (RIT) in TROP-2 (+)TNBC tumor-bearing model. Based on the camelid antibody, we developed a TROP-2 targeted recombinant antibody NY003. NY003 was conjugated with DFO and DTPA for 89Zr and 177Lu radiolabelling, respectively. The theranostic potential of [89Zr]Zr-DFO-NY003/[177Lu]Lu-DTPA-NY003 was evaluated through immunoPET, SPECT imaging, and RIT studies in the subcutaneous TROP-2 positive TNBC xenograft mice model. Results The high binding affinity of NY003 to TROP-2 was verified through ELISA. The radiochemical purity of [89Zr]Zr-DFO-NY003/[177Lu]Lu-DTPA-NY003 exceeded 95% and remained stable within 144h p.i. in vitro. ImmunoPET and SPECT imaging showed the specific accumulation of [89Zr]Zr-DFO-NY003/[177Lu]Lu-DTPA-NY003 in MDA-MB-231 tumors and gradually increased with the time tested, significantly higher than that in control groups (P

The clinical use of nuclear medicine imaging and therapy in pancreatic neuroendocrine tumors has been greatly strengthened since the approval of 68Ga-DOTATATE and 177Lu-DOTATATE. However, many aspects are still under discussion. In this 2-part article, we aim to collect and discuss current evidence of molecular imaging and peptide receptor radionuclide therapy (PRRT) in pancreatic neuroendocrine tumor. In the first part, we will address some critical aspects of 68Ga-SSAs imaging, including diagnostic efficacy, recurrence detection and follow-up, patient selection for PRRT, and pitfalls in image interpretation. Besides, we will also briefly discuss the role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography, special imaging strategy in regard to insulinoma, and the status of radiolabeled somatostatin receptor antagonist. In the second part, we aim to review the current evidence of PRRT in pancreatic neuroendocrine tumor, focusing on efficacy and safety in particular. We will also introduce the recent development of PRRT, including PRRT in high-grade neuroendocrine neoplasms, retreatment PRRT, upfront PRRT, PRRT in the setting of neoadjuvant therapy and conversion therapy, combination therapies with PRRT, PRRT with αradionuclides, and PRRT with antagonists.

Many management strategies are available for pancreatic neuroendocrine neoplasms with liver metastases. However, a lack of biological, molecular, and genomic information and an absence of data from rigorous trials limit the validity of these strategies. This review presents the viewpoints from an international conference consisting of several expert working groups. The working groups reviewed a series of questions of particular interest to clinicians taking care of patients with pancreatic neuroendocrine neoplasms with liver metastases by reviewing the existing management strategies and literature, evaluating the evidence on which management decisions were based, developing internationally acceptable recommendations for clinical practice, and making recommendations for clinical and research endeavors. The review for each question will be followed by recommendations from the panel.

Abstract Background A variety of external factors might seriously degrade PET image quality and lead to inconsistent results. The aim of this study is to explore a potential PET image quality assessment (QA) method with deep learning (DL). Methods A total of 89 PET images were acquired from Peking Union Medical College Hospital (PUMCH) in China in this study. Ground-truth quality for images was assessed by two senior radiologists and classified into five grades (grade 1, grade 2, grade 3, grade 4, and grade 5). Grade 5 is the best image quality. After preprocessing, the Dense Convolutional Network (DenseNet) was trained to automatically recognize optimal- and poor-quality PET images. Accuracy (ACC), sensitivity, specificity, receiver operating characteristic curve (ROC), and area under the ROC Curve (AUC) were used to evaluate the diagnostic properties of all models. All indicators of models were assessed using fivefold cross-validation. An image quality QA tool was developed based on our deep learning model. A PET QA report can be automatically obtained after inputting PET images. Results Four tasks were generated. Task2 showed worst performance in AUC,ACC, specificity and sensitivity among 4 tasks, and task1 showed unstable performance between training and testing and task3 showed low specificity in both training and testing. Task 4 showed the best diagnostic properties and discriminative performance between poor image quality (grade 1, grade 2) and good quality (grade 3, grade 4, grade 5) images. The automated quality assessment of task 4 showed ACC = 0.77, specificity = 0.71, and sensitivity = 0.83, in the train set; ACC = 0.85, specificity = 0.79, and sensitivity = 0.91, in the test set, respectively. The ROC measuring performance of task 4 had an AUC of 0.86 in the train set and 0.91 in the test set. The image QA tool could output basic information of images, scan and reconstruction parameters, typical instances of PET images, and deep learning score. Conclusions This study highlights the feasibility of the assessment of image quality in PET images using a deep learning model, which may assist with accelerating clinical research by reliably assessing image quality.

Abstract Background This pilot study is aimed to perform a pilot visualization study to investigate in vivo fibroblast activation in non-ischemic cardiomyopathies by 68Ga-FAPI-04 PET/CT. Methods Twenty-nine consecutive patients with symptomatic non-ischemic cardiomyopathies who underwent 68Ga-FAPI-04 PET/CT were prospectively recruited. Clinical characteristics and echocardiographic parameters were recorded. Cardiac uptake was quantified by standardized uptake values (SUVmax , SUVmean, SUVR) and left ventricular metabolism volume. The relationship between 68Ga-FAPI-04 uptake with clinical and echocardiography parameters was investigated. Results Heterogeneous 68Ga-FAPI-04 uptake was observed in different subtypes of non-ischemic cardiomyopathies. Twenty-two (75.9%) patients showed elevated 68Ga-FAPI-04 uptake in the left ventricle, and 10 (34.5%) patients also showed slightly diffuse elevated uptake in the right ventricle. Cardiac uptake values were significantly correlated with enlarged ventricular volume evaluated by echocardiography. Conclusion FAPI PET/CT presents a potential value for in vivo visualization and quantification of fibroblast activation on the molecular level. Further study is warranted for investigating the theranostic and prognostic value of elevated FAP signal.

Objective:. Different SSTR2 antagonists have been developed. This study aims to evaluate the impact of different peptides and chelators on the diagnostic performance of SSTR2 antagonists in well-differentiated NETs. Methods:. In this prospective study, participants were equally randomized into 2 arms: arm A, participants would undergo a whole-body 68Ga-NODAGA-LM3 PET/CT scan on the first day and 68Ga-DOTA-LM3 PET/CT scan on the second day; arm B, participants would undergo a whole-body 68Ga-NODAGA-LM3 PET/CT scan on the first day and 68Ga-NODAGA-JR11 PET/CT scan on the second day. Biodistribution in normal organs, lesion detection ability, and tumor uptakes were compared within each arm. Results:. A total of 40 participants (age, 49.5 ± 13.4, 21 men), 20 in each arm, were recruited in the study. In arm A, 68Ga-DOTA-LM3 showed lower background. However, the lesion detection ability (overall lesion detected, 445 vs 548; P = .005) and the lesion uptake (overall lesions SUVmax, 19.8 ± 17.2 vs 35.3 ± 28.8; P < .001) was significantly lower than those of 68Ga-NODAGA-LM3. In arm B, both 68Ga-NODAGA-LM3 and 68Ga-NODAGA-JR11 showed similar biodistribution and lesion uptake (SUVmax, 28.5 ± 23.8 vs 25.0 ± 20.0; P < .001) despite minor differences. The lesion detection ability was the same between these 2 tracers (overall lesion detected, 503 vs 503). Conclusions:. The diagnostic performance of SSTR2 antagonists was sensitive to chelators. Both 68Ga-NODAGA-LM3 and 68Ga-NODAGA-JR11 outperformed 68Ga-DOTA-LM3 with higher lesion uptake and detection ability, of which 68Ga-NODAGA-LM3 had marginally but significantly higher lesion uptake.

Abstract Background The maximum likelihood activity and attenuation (MLAA) reconstruction algorithm has been proposed to jointly estimate tracer activity and attenuation at the same time, and proven to be a promising solution to the CT attenuation correction (CT-AC) artifacts in PET images. This study aimed to perform a quantitative evaluation and clinical validation of the MLAA method. Methods A uniform cylinder phantom filled with 18F-FDG solution was scanned to optimize the reconstruction parameters for the implemented MLAA algorithm. 67 patients who underwent whole-body 18F-FDG PET/CT scan were retrospectively recruited. PET images were reconstructed using MLAA and clinical standard OSEM algorithm with CT-AC (CT-OSEM). The mean and maximum standardized uptake values (SUVmean and SUVmax) in regions of interest (ROIs) of organs, high uptake lesions and areas affected by metal implants and respiration motion artifacts were quantitatively analyzed. Results In quantitative analysis, SUVs in patient’s organ ROIs between two methods showed R 2 ranging from 0.91 to 0.98 and k ranging from 0.90 to 1.06, and the average SUVmax and SUVmean differences between two methods were within 10% range, except for the lung ROI, which was 10.5% and 16.73% respectively. The average SUVmax and SUVmean differences of a total of 117 high uptake lesions were 7.25% and 7.10% respectively. 20 patients were identified to have apparent respiration motion artifacts in the liver in CT-OSEM images, and the SUVs differences between two methods measured at dome of the liver were significantly larger than measured at middle part of the liver. 10 regions with obvious metal artifacts were identified in CT-OSEM images and the average SUVmean and SUVmax differences in metal implants affected regions were reported to be 52.90% and 56.20% respectively. Conclusions PET images reconstructed using MLAA are clinically acceptable in terms of image quality as well as quantification and it is a useful tool in clinical practice, especially when CT-AC may cause respiration motion and metal artifacts. Moreover, this study also provides technical reference and data support for the future iteration and development of PET reconstruction technology of SUV accurate quantification.

Objectives Little is known about the clinical impact of germline/somatic mutations of PTPN11 in acute leukemia. The aim of this study was to investigate the clinical characteristics and prognostic impact of PTPN11 mutations in patients with acute myeloid leukemia (AML).Methods: Seventy-four patients with PTPN11 mutation-positive AML treated at our institution were enrolled in this study. The prevalence of PTPN11 mutations was examined using targeted next-generation sequencing technology, and patients with AML and PTPN11 mutations were screened. Clinical characteristics, prognostic impact, and association between PTPN11 mutations and other mutations were analyzed retrospectively.Results: PTPN11 mutations co-occurred more commonly with DNMT3A, NPM1, and FLT3 internal tandem duplication mutations. Compared with PTPN11 wild-type (WT) patients, PTPN11 mutation-positive AML patients presented with higher white blood cell (WBC) and platelet (PLT) counts. In 74 PTPN11 positive AML patients, PTPN11 mutations had an adverse effect on overall survival (OS) (62.5%) and a negative prognostic effect on event-free survival (EFS) (50%). Allo-hematopoietic stem cell transplantation (HSCT) abrogated the negative effect of mutations in PTPN11; the OS and EFS of AML patients with PTPN11 mutations who received transplantation were longer than those of AML patients with PTPN11 mutations who did not undergo allo-HSCT (P = 0.001, EFS; P

Pancreatic cancer is one of the most lethal malignancies in the world. Cancer-associated fibroblasts are one of the main components of tumor microenvironment in pancreatic cancer and play an essential role in tumor progression. Fibroblast activation protein that is expressed in specific subtypes of cancer-associated fibroblasts promotes tumor growth and is related to poor survival. Recent researches have preliminarily demonstrated a promising potential of radiopharmaceuticals targeting fibroblast activation protein in diagnosis and therapy of pancreatic cancer. This article comprehensively reviews the current development and clinical translation of fibroblast activation protein inhibitor-targeting radiopharmaceuticals in pancreatic cancer and provides significant perspectives for future investigations.

Abstract Myeloproliferative neoplasms (MPNs) with concurrent BCR‐ABL1 fusion gene and CALR mutation are especially rare. We report a patient with coexisting BCR‐ABL1 fusion gene, CALR, and TET2 mutations who was treated with the combination of the second‐generation TKI nilotinib and JAK1/JAK2 inhibitor ruxolitinib.

Abstract The optimal method of tumor burden evaluation in newly diagnosed multiple myeloma (NDMM) is yet to be determined. This study aimed to compare the value of 11C-acetate positron-emission tomography (PET)/computed tomography (CT) (AC-PET and 18F-fluorodeoxyglucose PET/CT (FDG-PET) in the assessment of tumor burden in NDMM. This study evaluated 64 NDMM patients between February 2015 and July 2018. AC-PET and FDG-PET were used to assess myeloma lesions. The clinical data, imaging results, and their correlations were analyzed. Diffuse bone marrow uptake in AC-PET was significantly correlated with biomarkers for tumor burden, including serum hemoglobin (P = 0.020), M protein (P = 0.054), the percentage of bone marrow plasma cells (P 6.0 in AC-PET, but not in FDG-PET, predicted a higher probability of disease progression and shorter progression-free survival (P

BackgroundCyclin-dependent kinase 4/6 inhibitor (CDK4/6i) has become the commonest first-line treatment of hormonal receptor positive and human epidermal growth factor receptor 2 negative (HR+/HER2-) metastatic breast cancer (MBC). However, therapy is quite individualized after progression of disease (PD) when CDK4/6i fails. Estrogen receptor (ER) status of metastatic lesions of bone, lung or liver might be different from the primary tumor and biopsy of metastatic lesions was invasive and not always available. Prediction of treatment response after PD of CDK4/6i remains unsolved. 18F-fluoroestradiol (FES) PET/CT could non-invasively reveal ER expression both in primary and metastatic breast cancer and recognize heterogeneity of ER status.Case presentationA 70-year-old woman with Parkinson’s disease, osteoporosis and cardiovascular co-morbidity was diagnosed with HR+/HER2- breast cancer (pT2N2M0, stage IIIa). Three years later, she developed metastases in right lung and pleura with pleural effusion and received palbociclib + letrozole. After 8 months the disease progressed, and 18F-FES PET/CT revealed multiple ER-positive pleural lesions and ER-negative pulmonary nodules after PD and the progression-free survival (PFS) of first-line CDK4/6i was 8 months. Since most of the metastatic lesions were ER-positive, abemaciclib + fulvestrant were chosen as the second-line CDK4/6i treatment and the PFS was 15 months. Another 18F-FES PET/CT showed a new ER-positive pleural mass with multiple ER-negative pulmonary nodules. Since 18F-FES PET/CT revealed that the dominant lesions were still ER-positive, dalpiciclib + exemestane + fulvestrant were prescribed as the third-line CDK4/6i treatment. Currently the patient’s disease had been stable for 2 months.ConclusionThis case demonstrated that 18F-FES PET/CT could show ER heterogeneity non-invasively and reveal the treatment responses a predictive imaging tool of serial second- and third-line of CDK4/6i treatments when first-line CDK4/6i failed in HR+/HER2- MBC. So long as the dominant or newly-developed metastatic lesion was ER-positive on 18F-FES PET after first-line CDK4/6i, the patient might show certain therapeutic response towards endocrine-based treatment including second- and third-line of CDK4/6i, and thus increased the time to chemotherapy (TTC).

Abstract Background With the increased understanding of heart disease, microvascular angina (MVA) is receiving greater attention from clinicians. Studies have shown that patients with MVA have significantly higher major cardiovascular events and all-cause mortality than the control population, and the search for effective treatments is of great clinical importance. Both basic and clinical studies have shown that Qi-Jing Hui-Xin Decoction (QJHX) can relieve angina symptoms and improve clinical efficacy, but there is a lack of high-quality clinical studies to provide a research basis. This article introduces the evaluation protocol of QJHX for the adjunctive treatment of MVA. Methods/design This is a prospective randomized controlled trial. The trial will enroll 150 patients with MVA. On the basis of Western drug treatment, patients will be randomized into two groups, and the experimental group will receive QJHX treatment for 12 weeks and follow-up at 24 week. The primary indicators are the clinical efficacy of angina pectoris and the evidence of traditional Chinese medicine (TCM) efficacy. Secondary indicators are the Seattle Angina Scale score, serum lipid levels, electrocardiogram, and echocardiogram diagnosis. Additional indicators are endothelial function and immunoinflammatory factors. Adverse events will be monitored throughout the trial. Discussion Integrated traditional Chinese and Western medicine is commonly used for angina in China. This study will evaluate the clinical effectiveness and safety of adding QJHX based on standardized Western medications. The results of the trial will provide high-level clinical research-based evidence for the application of QJHX in MVA. Trial registration Chinese Clinical Trial Registry ChiCTR1900027015 . Registered on 28 October 2019.

Abstract Background Coronary heart disease (CHD) has become one of the biggest health problems in the world. Stable angina is a common clinical type of CHD with poor prognosis and high mortality. Although there are various interventions for stable angina, none of them can significantly reduce mortality. Both basic and clinical research have shown that Suxiao Jiuxin Pill (SJP) can relieve the symptoms of angina pectoris and improve the clinical efficacy, but there is a lack of high-quality clinical research to provide research-based evidence. We design a randomized, double-blind, placebo-controlled trial to evaluate the efficacy of SJP for stable angina. Methods/design This is a prospective, randomized, double-blind, placebo-controlled, and multicenter trial. The trial will enroll 324 participants with chronic stable angina (Qi Stagnation and Blood Stasis syndrome). All participants will have received the conventional therapy of chronic stable angina. Participants will be randomized into two groups, conventional therapy plus SJP group and conventional therapy plus placebo group. Eligible participants will receive either SJP or placebo (five pills administered orally, three times daily) in addition to conventional treatment for 24 weeks. The primary outcomes are the symptom improvement rate of angina from baseline to 4 weeks after inclusion and major adverse cardiovascular events (MACE). The secondary outcomes are angina classification (CCS), improvement of traditional Chinese medicine (TCM) syndromes, Seattle Angina Scale score, the dosage of emergency drugs and the stopping rate, and electrocardiogram (EKG) efficacy. Adverse events will be monitored throughout the trial. Discussion Integrated traditional Chinese and Western Medicine is commonly used for angina in China. This study will evaluate the clinical effectiveness and safety of SJP for angina. The results of the trial will provide high-level clinical research-based evidence for the application of SJP instable angina. Trial registration This study protocol was registered on 14 March 2019. The registration number is ChiCTR1900021876 on the Chinese Clinical Trial Registry.

BackgroundLangerhans cell histiocytosis (LCH) is a rare disease caused by the clonal expansion of CD1a+/CD207+ LCH cells. The thyroid involvement in LCH has mostly been described in case reports.MethodsWe retrospectively evaluated the clinical characteristics, diagnosis, and treatment of 27 children and adult patients with thyroid LCH in our center between 2010 and 2021.ResultsThe incidence of thyroid LCH was 14.00% (7/50) in children and 10.10% (20/198) in adults, respectively. Among patients with thyroid involvement, 81.5% presented with diabetes insipidus (DI) as the first symptom, and 51.9% complained of neck swelling or mass. Children and adults with thyroid LCH had higher frequencies of the hypothalamic-pituitary axis (HPA) (children: 100% vs. 62.8%, P=0.05; adult: 95% vs. 42.1%, P

Candida glabrata is the second or third most common Candida-associated species isolated from hospital-acquired infections, surpassing even C. albicans in some hospitals. With the rapid progression of the disease course of C. glabrata infections, there is an urgent need for a rapid and sensitive on-site assay for clinical diagnosis. Isothermal amplification is a recently developed method for rapid nucleic acid detection that is being increasingly used for on-site detection, especially recombinase polymerase amplification (RPA). RPA combined with lateral flow strips (LFS) can rapidly amplify and visually detect the target gene within 20 min. The whole detection process can be controlled within 30–60 min by rapid sample pre-treatment. In this study, RPA-LFS was used to amplify the internal transcribed spacer region 2 gene of C. glabrata. The primer–probe design was optimized by introducing base mismatches (probe modification of one base) to obtain a highly specific and sensitive primer–probe combination for clinical sample detection. RPA-LFS was performed on 23 common clinical pathogens to determine the specificity of the assay system. The RPA-LFS system specifically detected C. glabrata without cross-reaction with other fungi or bacteria. Gradient dilutions of the template were tested to explore the lower limit of detection of this detection system and to determine the sensitivity of the assay. The sensitivity was 10 CFU/µL, without interference from genomic DNA of other species. The RPA-LFS and qPCR assays were performed on 227 clinical samples to evaluate the detection performance of the RPA-LFS system. Eighty-five samples were identified as C. glabrata, representing a detection rate of 37.5%. The results were consistent with qPCR and conventional culture methods. The collective findings indicate a reliable molecular diagnostic method for the detection of C. glabrata, and to meet the urgent need for rapid, specific, sensitive, and portable clinical field-testing.

A 47-year-old female with cardiac dysfunction and lymphadenopathy underwent 18FDG PET/CT and 68Ga-FAPI-04 imaging for tumor screening. Mild uptake in the left ventricular wall was detected on the oncology 18FDG PET/CT. True myocardiac-involvement could not be distinguished with physiological uptake. The following 68Ga-FAPI-04 showed intense heterogeneous uptake in the left ventricular wall, particularly in the septum and apex area, corresponding with the late gadolinium enhancement regions shown by cardiac MR. Intense uptake was also noted in the mediastinal and bilateral hilar lymph nodes. Endomyocardial biopsy demonstrated sarcoidosis.

Abstract Background Lymphangioleiomyomatosis (LAM) is a rare multisystem disease characterized by cystic lung disease and extrapulmonary manifestations, including lymphatic system disorder. The objective of this study was to investigate the findings of 68Ga-NOTA-Evans Blue (NEB) PET/CT in LAM and compare it with that of 99mTc-ASC lymphoscintigraphy. Methods Ten patients diagnosed with LAM according to the American Thoracic Society/Japanese Respiratory Society guidelines for LAM were recruited in this study. PET/CT acquisition was performed at 20 to 40 min after subcutaneous injection of 68Ga-NEB into the first interdigital spaces of both feet (0.3 ml, 37 MBq/foot). All subjects also underwent 99mTc-antimony sulfide colloid (ASC) lymphoscintigraphy within a week for comparison. Results 68Ga-NEB PET/CT displayed various lymphatic system abnormalities in 10 (100%) of 10 patients. These included pulmonary lymphatic abnormalities in 10 (100%) of 10 patients, enlarged lymph nodes in 5 (50%), lymphangioleiomyomas in 2 (20%), dilation of the lumbar trunk and/or iliac lymph vessels in 5 (50%), thoracic duct dilation in 2 (20%), chylous effusion in 1 (10%). For pulmonary lymphatic abnormalities, the positive rates of 68Ga-NEB PET/CT and 99mTc-ASC lymphoscintigraphy were 100% (10/10) and 10% (1/10), respectively (P

Abstract Background Dynamic PET with kinetic modeling was reported to be potentially helpful in the assessment of hepatic malignancy. In this study, a kinetic modeling analysis was performed on hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) from dynamic FDG positron emission tomography/computer tomography (PET/CT) scans. Methods A reversible two-tissue compartment model with dual blood input function, which takes into consideration the blood supply from both hepatic artery and portal vein, was used for accurate kinetic modeling of liver dynamic 18F-FDG PET imaging. The blood input functions were directly measured as the mean values over the VOIs on descending aorta and portal vein respectively. And the contribution of hepatic artery to the blood input function was optimization-derived in the process of model fitting. The kinetic model was evaluated using dynamic PET data acquired on 24 patients with identified hepatobiliary malignancy. 38 HCC or ICC identified lesions and 24 healthy liver regions were analyzed. Results Results showed significant differences in kinetic parameters $${K}_{1}-{k}_{4}$$ K 1 - k 4 , blood supplying fraction $${f}_{A}$$ f A , and metabolic rate constant $${K}_{i}$$ K i between malignant lesions and healthy liver tissue. And significant differences were also observed in $${K}_{1}$$ K 1 , $${k}_{3}$$ k 3 , $${f}_{A}$$ f A and $${K}_{i}$$ K i between HCC and ICC lesions. Further investigations of the effect of SUV measurements on the derived kinetic parameters were conducted. And results showed comparable effectiveness of the kinetic modeling using either SUVmean or SUVmax measurements. Conclusions Dynamic 18F-FDG PET imaging with optimization-derived hepatic artery blood supply fraction dual-blood input function kinetic modeling can effectively distinguish malignant lesions from healthy liver tissue, as well as HCC and ICC lesions.

Tumor-induced rickets/osteomalacia (TIR/O) severely impairs bone microarchitecture and bone strength. However, no study has described the microarchitectural quality of bone in adolescent patients with TIR/O. TIR/O affects bone quality more severely than the inherited causes of hypophosphatemia, the most common form of which is X-linked hypophosphatemia (XLH). Nevertheless, differences of the microarchitectural quality of the bone between TIR/O and XLH have never been clarified. Therefore, in this study, we used high-resolution peripheral quantitative computed tomography to assess bone microarchitecture in five Chinese adolescent TIR/O patients, and these were compared with 15 age- and gender-matched XLH patients as well as 15 age- and gender-matched healthy controls. Compared with the healthy controls, the TIR/O patients presented with significantly lower volumetric bone mineral densities (vBMDs), severely affected bone microarchitecture, and profoundly weaker bone strength. The distal tibia was more severely affected than the distal radius. Compared with the XLH patients, the TIR/O patients showed deteriorated bone quality notably at the distal tibia and in the cancellous compartment, reflected by 45.9% lower trabecular vBMD (p = 0.029), 40.2% lower trabecular fraction (p = 0.020), 40.6% weaker stiffness (p = 0.058), and 42.7% weaker failure load (p = 0.039) at the distal tibia. The correlation analysis showed that a higher level of serum FGF23 and a lower level of serum phosphate were associated with a poorer bone microarchitecture and a weaker estimated bone strength in the hypophosphatemic patients of our study. In conclusion, our study demonstrated significantly lower vBMDs, severely impaired bone microarchitecture, and profoundly weaker bone strength in Chinese adolescent patients with TIR/O, notably at the distal tibia, compared with the same parameters in age- and sex-matched healthy controls and XLH patients, which was possibly caused by excessive FGF23 production and secretion, chronically severe hypophosphatemia, and weak mechanical stimulus at the lower extremities. These findings further our understanding of the impact of different kinds of hypophosphatemic rickets/osteomalacia on bone quality.

Abstract. Pancreatic neuroendocrine neoplasms (pNENs) are highly heterogeneous, and the management of pNENs patients can be intractable. To address this challenge, an expert committee was established on behalf of the Chinese Pancreatic Surgery Association, which consisted of surgical oncologists, gastroenterologists, medical oncologists, endocrinologists, radiologists, pathologists, and nuclear medicine specialists. By reviewing the important issues regarding the diagnosis and treatment of pNENs, the committee concluded evidence-based statements and recommendations in this article, in order to further improve the management of pNENs patients in China.

Abstract Purpose To develop and validate a machine learning model based on radiomic features derived from 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) images to preoperatively predict the pathological grade in patients with pancreatic ductal adenocarcinoma (PDAC). Methods A total of 149 patients (83 men, 66 women, mean age 61 years old) with pathologically proven PDAC and a preoperative 18F-FDG PET/CT scan between May 2009 and January 2016 were included in this retrospective study. The cohort of patients was divided into two separate groups for the training (99 patients) and validation (50 patients) in chronological order. Radiomics features were extracted from PET/CT images using Pyradiomics implemented in Python, and the XGBoost algorithm was used to build a prediction model. Conventional PET parameters, including standardized uptake value, metabolic tumor volume, and total lesion glycolysis, were also measured. The quality of the proposed model was appraised by means of receiver operating characteristics (ROC) and areas under the ROC curve (AUC). Results The prediction model based on a twelve-feature-combined radiomics signature could stratify PDAC patients into grade 1 and grade 2/3 groups with AUC of 0.994 in the training set and 0.921 in the validation set. Conclusion The model developed is capable of predicting pathological differentiation grade of PDAC based on preoperative 18F-FDG PET/CT radiomics features.

Abstract Purpose Papillary renal cell carcinoma (RCC) is the second most common subtype of RCC, after clear cell RCC. This study aimed to investigate the usefulness of FDG PET/CT in primary and recurrent papillary RCC, and the role of staging FDG PET/CT in predicting survival. Methods A total of 66 patients with histopathologically confirmed papillary RCC who underwent either staging or restaging FDG PET/CT scans (30 had staging scans only, 28 had restaging scans only, 8 had both) were retrospectively included in this study. The sensitivity and specificity of restaging FDG PET/CT for detecting recurrence were assessed by histopathology and/or clinical follow-up as standard reference. Results Staging FDG PET/CT scans were performed in 38 patients, of which 31 (81.5%) showed FDG-positive primary renal lesions. The SUVmax of high-grade (WHO grade 3 and 4) papillary RCCs were significantly higher than that of low-grade (WHO grade 1 and 2) tumors (9.44 ± 6.18 vs 4.83 ± 3.19, P = 0.008). The SUVmax was not significantly different between type 1 and type 2 papillary RCCs (5.71 ± 2.88 vs. 6.99 ± 5.57, P = 0.563). Of the 38 patients, 12 developed disease progression during the follow-up period. Patients with primary tumor SUVmax> 5.85 were associated with significantly shorter progression-free survival (PFS) than those with tumor SUVmax≤5.85 (P = 0.005). Restaging FDG PET/CT scans were performed in 36 patients with suspected recurrent papillary RCCs. FDG PET/CT showed a sensitivity and specificity of 100 and 72.7% for detecting recurrent disease. Comparison of PET/CT scans with CT/MRI imaging was available in 23 patients. FDG PET/CT revealed additional findings in 11 patients, mainly including lymph node and bone metastases. FDG PET/CT findings led to change in management in 5.3% (2/38) of patients in the staging setting and 16.7 (6/36) of patients in the restaging setting. Conclusions FDG PET/CT had a sensitivity of 81.5% for detecting primary papillary RCC, and tumor SUVmax derived from staging FDG PET/CT was a predictor of PFS. In the restaging process of papillary RCC, FDG PET/CT was very effective for detecting recurrent disease.

Abstract Background 99mTc-PYP scintigraphy provides differential diagnosis of ATTR cardiomyopathy (ATTR-CM) from light chain cardiac amyloidosis and other myocardial disorders without biopsy. This study was aimed to assess the diagnostic feasibility and the operator reproducibility of 99mTc-PYP quantitative SPECT. Method Thirty-seven consecutive patients who underwent a 99mTc-PYP thorax planar scan followed by SPECT and CT scans to diagnose suspected ATTR-CM were enrolled. For the quantitative SPECT, phantom studies were initially performed to determine the image conversion factor (ICF) and partial volume correction (PVC) factor to recover 99mTc-PYP activity concentration in the myocardium for calculating the standardized uptake value (SUV) (unit: g/ml). SUVmax was compared among groups of ATTR-CM, AL cardiac amyloidosis, and other pathogens (others) and among categories of Perugini visual scores (grades 0–3). The intra- and inter-operator reproducibility of quantitative SPECT was verified, and the corresponded repeatability coefficient (RPC) was calculated. Results The ICF was 79,327 Bq/ml to convert count rate in pixel to 99mTc activity concentration. PVC factor as a function of the measured activity concentration ratio in the myocardium and blood-pool was [y = 1.424 × (1 − exp(− 0.759 × x)) + 0.104]. SUVmax of ATTR-CM (7.50 ± 2.68) was significantly higher than those of AL (1.96 ± 0.35) and others (2.00 ± 0.74) (all p < 0.05). SUVmax of grade 3 (8.95 ± 1.89) and grade 2 (4.71 ± 0.23) were also significantly higher than those of grade 1 (1.92 ± 0.31) and grade 0 (1.59 ± 0.39) (all p < 0.05). Correlation coefficient (R 2) of SUVmax reached 0.966 to 0.978 with only small systematic difference (intra = − 0.14; inter = − 0.23) between two repeated measurements. Intra- and inter-operator RPCs were 0.688 and 0.877. Conclusions 99mTc-PYP quantitative SPECT integrated with adjustable PVC factors is feasible to quantitatively and objectively assess the burden of cardiac amyloidosis for diagnosis of ATTR-CM.

Abstract Background The study aimed to establish a 68Ga-FAPI-04 kinetic model in hepatic lesions, to determine the potential role of kinetic parameters in the differentiation of hepatocellular carcinoma (HCC) from non-HCC lesions. Material and methods Time activity curves (TACs) were extracted from seven HCC lesions and five non-HCC lesions obtained from 68Ga-FAPI-04 dynamic positron emission tomography (PET) scans of eight patients. Three kinetic models were applied to the TACs, using image-derived hepatic artery and/or portal vein as input functions. The maximum standardized uptake value (SUVmax) was taken for the lesions, the hepatic artery, and for the portal veins—the mean SUV for all healthy regions. The optimum model was chosen after applying the Schwartz information criteria to the TACs, differences in model parameters between HCC, non-HCC lesions, and healthy tissue were evaluated with the ANOVA test. Results A reversible two-tissue compartment model using both the arterial as well as venous input function was most preferred and showed significant differences in the kinetic parameters V ND, V T, and BPND between HCC, non-HCC lesions, and healthy regions (p

BackgroundThe purpose of this study is to compare the sensitivity of 68Ga-DOTA-JR11 and 68Ga-DOTA-TATE PET/CT for detecting the responsible tumor of tumor-induced osteomalacia (TIO) and investigate if 68Ga-DOTA-JR11 PET/CT can identify the culprit tumor of TIO in multiple suspicious lesions in 68Ga-DOTA-TATE PET/CT.MethodsA total of 19 patients with suspected TIO were prospectively recruited in this study. Each patient underwent whole-body PET/CT scan 40–60 min postinjection using 68Ga-DOTA-TATE and 68Ga-DOTA-JR11 on the same PET/CT, respectively in sequence, and on consecutive days. The diagnosis of TIO was confirmed by the combination of the postsurgical pathological results of the tumor and clinical information.ResultsAmong the 19 patients with TIO who were included in this study, culprit tumors from all patients were confirmed pathologically. 68Ga-DOTA-TATE PET/CT positively identified the causative tumor in 18/19 patients, whereas 68Ga-DOTA-JR11 PET/CT was positive in 11/19 patients (94.7% vs. 57.9%, respectively; p < 0.05). 68Ga-DOTA-TATE PET/CT demonstrated more than one increased focal activity in 7 patients for a total of 16 lesions (3 lesions each in 2 patients and 2 lesions each in the rest 5 patients). However, seven of these 16 lesions showed concordant results on 68Ga-DOTA-JR11 PET/CT by demonstrating increased activity (one lesion in each of the 7 patients). The surgical specimens of the lesions in these 7 patients confirmed the phosphaturic mesenchymal tumor. A total of 11 culprit tumors were positive in both 68Ga-DOTA-TATE and 68Ga-DOTA-JR11 PET/CT. The SUVmax of 11 culprit tumors was significantly higher on 68Ga-DOTA-TATE PET/CT compared with that on 68Ga-DOTA-JR11 PET/CT (17.8 ± 12.5 vs. 6.8 ± 6.2; p < 0.05).Conclusions68Ga-DOTA-TATE PET/CT is more sensitive to 68Ga-DOTA-JR11 PET/CT in the detection of the culprit tumor of TIO. However, 68Ga-DOTA-JR11 PET/CT might be helpful to identify the tumor in multiple suspicious lesions in 68Ga-DOTA-TATE PET/CT.Clinical Trial Registrationclinicaltrials.gov, identifier NCT 04689893.

Endothelial progenitor cells (EPCs) play a major role in regulating pulmonary vascular remodeling during pulmonary arterial hypertension (PAH) development. Several preclinical and clinical trials of EPCs transplantation have been performed for the treatment of PAH. However, there is no reliable method to monitor real-time cell trafficking and quantify transplanted EPCs. Here in this paper we isolated EPCs from human peripheral blood, identified their functional integrity, and efficiently labeled the EPCs with 89Zr-oxine and DiO. Labeled EPCs were injected into the tail vein of normal and PAH rats to be tracked in vivo. From the microPET/CT images, we found EPCs were distributed primarily in the lung at 1 h and then migrated to the liver and spleen. We could observe the 3,3′ dioctadecyloxacarbocyanine perchlorate (DiO)-labeled EPCs binding in the pulmonary vasculature by CellVizio confocal. The result of quantitative analysis revealed significantly higher accumulation of EPCs in the lungs of PAH rats than in those of healthy rats. The distribution and higher accumulation of EPCs in the lungs of PAH rats could help to evaluate the safety and provide evidence of effectiveness of EPC therapy.

Abstract Background Osteoporotic vertebral compression fractures (OVCF) is a common and often debilitating complication of osteoporosis, leading to significant morbidity and increased mortality. Percutaneous vertebroplasty (PVP) and Percutaneous kyphoplasty (PKP) are recommendable surgical treatments for OVCF. Objective To evaluate PVP/PKP utilisation and their related direct medical costs for OVCF treatment in China from the payer perspective. Methods A population-based medical claims database of a metropolitan city in China was analysed from the payer perspective, which included all inpatient claims from 01/01/2015 to 31/12/2017. All vertebral fractures patients that met the eligibility criteria (aged ≥50 years old, having vertebral fracture diagnosis, without unrelated diseases diagnoses such as tumour and scoliosis, received PVP/PKP) were deemed as OVCF patients. Baseline characteristics, surgery rate, length of stay in hospital, time to re-surgery, and costs (including costs per hospitalisation and annual costs) were described. Survival analysis function was used to estimate the re-surgery rate. Results Of the 50,686 patients with OVCF identified, 14,527 (28.66%) received a total number of 15,599 records of PVP/PKP surgeries from 2015 to 2017. Mean age was 75 at the first surgery captured in the database analysis period; females accounted for 79.54% of all cases. The median length of surgery stay was 9 days. Cumulative re-surgery rates were 1.22% in 30 days, 2.58% in 90 days, 3.61% in 183 days, 5.42% in 1 year, and 7.95% in 2 years. There was no significant difference in re-surgery rate between PVP and PKP (p = 0.3897). The median time to the re-surgery was 139 days. Mean costs per PVP/PKP-related hospitalisation were 35,906 CNY/5122 USD (34,195 CNY/4878USD for PVP, 44,414 CNY/6336 USD for PKP, p

Abstract Background Chronic alcohol consumption initially leads to asymptomatic left ventricular dysfunction, but can result in myocardial impairment and heart failure if ongoing. This study sought to characterize myocardial tissues and oxidative metabolism in asymptomatic subjects with chronic alcohol consumption by quantitative cardiovascular magnetic resonance (CMR) and 11C-acetate positron emission tomography (PET)/computed tomography (CT). Methods Thirty-four male subjects (48.8 ± 9.1 years) with alcohol consumption > 28 g/day for > 10 years and 35 age-matched healthy male subjects (49.5 ± 9.7 years) underwent CMR and 11C-acetate PET/CT. Native and post T1 values and extracellular volume (ECV) from CMR and Kmono and K1 from PET imaging were measured. Quantitative measurements by CMR and PET imaging were compared between subjects with moderate to heavy alcohol consumption and healthy controls, and their correlations were also analyzed. Results Compared to healthy controls, subjects with alcohol consumption showed significantly shorter native T1 (1133 ± 65 ms vs. 1186 ± 31 ms, p 0.05). In contrast, subjects with heavy alcohol consumption showed significantly lower Kmono values compared to those with moderate alcohol consumption (52.9 ± 12.1 min− 1 × 10− 3 vs. 63.7 ± 9.2 min− 1 × 10− 3, p = 0.012). Strong and moderate correlations were found between K1 and ECV in healthy controls (r = 0.689, p = 0.013) and subjects with moderate alcohol consumption (r = 0.518, p = 0.048), respectively. Conclusion Asymptomatic men with heavy alcohol consumption have detectable structural and metabolic changes in myocardium on CMR and 11C-acetate PET/CT. Compared with quantitative CMR, 11C-acetate PET/CT imaging may be more sensitive for detecting differences in myocardial damage among subjects with moderate to heavy alcohol consumption.

Brown adipose tissue (BAT) is important in monitoring energy homeostasis and cancer cachexia. Different from white adipose tissue, BAT is characterized by the presence of a large number of mitochondria in adipocytes. Translocator protein 18 kDa (TSPO), a critical transporter, is expressed in the outer membrane of mitochondria. We speculated that [18F]DPA714, a specific TSPO tracer, may monitor BAT activity in tumor-bearing mice in vivo. We first analyzed the radioactive uptake of positron emission tomography (PET) tracers in BAT of CT26 xenograft mice with 18F-fluorodeoxyglucose ([18F]FDG) and [18F]DPA714. We also studied the BAT uptake of [18F]DPA714 in CT26, A549 and LLC tumor models. The dynamic distribution of [18F]FDG is quite variable among animals, even in mice of the same tumor model (%ID/g-mean: mean ± SDM, 8.61 ± 8.90, n = 16). Contrarily, [18F]DPA714 produced high-quality and stable BAT imaging in different tumor models and different animals of the same model. Interestingly, %ID/g-mean of [18F]DPA714 in BAT was significantly higher on day 26 than that on day 7 in CT26 xenograft model. Taken together, these results strongly indicate the potential feasibility of [18F]DPA714 PET imaging in investigating BAT and energy metabolism during tumor progression in preclinical and clinical study.

Knottin is a cystine knot peptide. Here, the authors develop a knottin-based tracer for positron emission tomography and demonstrate its ability to detect cancer and idiopathic pulmonary fibrosis through selective binding to integrin αvβ6.

BackgroundMolecular imaging targeting angiogenesis can specifically monitor the early therapeutic effect of antiangiogenesis therapy. We explore the predictive values of an integrin αvβ3-targeted tracer, 99mTc-PEG4-E[PEG4-c(RGDfK)]2 (99mTc-3PRGD2), for monitoring the efficacy of Endostar antiangiogenic therapy and chemotherapy in animal models.MethodsThe pancreatic cancer xenograft mice were randomly divided into four groups, with seven animals in each group and treated in different groups with 10 mg/kg/day of Endostar, 10 mg/kg/day of gemcitabine, 10 mg/kg/day of Endostar +10 mg/kg/day of gemcitabine at the same time, and the control group with 0.9% saline (0.1 ml/day). 99mTc-3PRGD2 scintigraphic imaging was carried out to monitor therapeutic effects. Microvessel density (MVD) was measured using immunohistochemical staining of the tumor tissues. The region of interest (ROI) of tumor (T) and contralateral corresponding site (NT) was delineated, and the ratio of radioactivity (T/NT) was calculated. Two-way repeated-measure analysis of variance (ANOVA) was used to assess differences between treatment groups.ResultsTumor growth was significantly lower in treatment groups than that in the control group (p < 0.05), and the differences were noted on day 28 posttreatment. The differences of 99mTc-3PRGD2 uptakes were observed between the control group and Endostar group (p = 0.033) and the combined treatment group (p < 0.01) on day 7 posttreatment and on day 14 posttreatment between the control group and gemcitabine group (p < 0.01). The accumulation of 99mTc-3PRGD2 was significantly correlated with MVD (r = 0.998, p = 0.002).ConclusionWith 99mTc-3PRGD2 scintigraphic imaging, the tumor response to antiangiogenic therapy, chemotherapy, and the combined treatment can be observed at an early stage of the treatments, much earlier than the tumor volume change. It provides new opportunities for developing individualized therapies and dose optimization.

PurposeTo evaluate the role of the pre-treatment cervical and lymph node (LN) metabolic parameters of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) for locally advanced cervical cancer (LACC) patients receiving concurrent chemoradiotherapy or radiotherapy.Methodswe reviewed 125 consecutive patients with LACC who underwent pre-treatment 18F-FDG PET/CT examination and concurrent chemoradiotherapy or radiotherapy from February 2010 to December 2015 at our institute. The mean standardized uptake value (SUVmean), maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of cervical lesion and lymph node (LN) were recorded. Receiver operator characteristic curve, C-index, Kaplan-Meier method, and Cox proportional hazards models were performed.ResultsThe median follow-up was 62 months (range, 4-114 months). For 125 included patients with cervical cancer, the 5-year overall survival (OS), disease-free survival (DFS), local control (LC) and distant metastasis-free survival (DMFS) rates were 83.6%, 75.1%, 92.3% and 79.9%, respectively. Cervical MTV (c-index 0.59-0.61) and cervical TLG (c-index 0.60-0.62) values calculated with a threshold of 40% SUVmax presented stronger prediction capability than cervical SUVmean (c-index 0.51-0.58) and cervical SUVmax (c-index 0.53-0.57) for OS, DFS, LC, and DMFS. In univariate analysis, cervical TLG ≥ 113.4 had worse DFS and DMFS. Cervical MTV ≥ 18.3 cm3 had worse OS and DMFS. In multivariate analysis, cervical TLG ≥ 113.4 implied worse OS, DFS, and DMFS. In either univariate or multivariate analyses, cervical SUVmean and cervical SUVmax had no statistically significant correlation with OS, DFS, LC and DMFS. For 55 cervical cancer patients with positive LN, LN SUVmax presented strongest prediction capability for OS (c-index = 0.79), DFS (c-index = 0.72), LC (c-index = 0.62), and DMFS (c-index = 0.79). In multivariate analysis, LN SUVmax remained significant biomarker linked to OS, DFS, and DMFS.ConclusionPre-treatment cervical and LN metabolic parameters were associated with survival outcomes in patients with LACC. In our study, we found that pre-treatment cervical TLG and LN SUVmax may be important prognostic biomarkers for OS, DFS, and DMFS. However, further prospective studies with a large number of patients are required to evaluate the value of the metabolic parameters in survival outcomes prediction.

We report a rare case of Cushing’s syndrome induced by an ectopic adrenocortical adenoma. A 57-year-old woman was diagnosed with adrenocorticotropic hormone (ACTH)-independent Cushing’s syndrome based on clinical manifestation and laboratory information. She was found to have a mass in the left renal hilum via contrast-enhanced computed tomography (CT). The mass was negative, as seen in somatostatin receptor imaging with 99mTc-hydrazinonicotinyl-Tyr3-octreotide (HYNIC-TOC), and showed mild fluorodeoxyglucose (FDG) activity via positron emission tomography (PET)/CT. The results of adrenal venous sampling suggested a left-side adrenal origin of hypercortisolism, possibly secreted by the mass in the renal hilum. Histopathology after surgical resection of the mass confirmed an ectopic adrenocortical adenoma, which was responsible for the patient’s Cushing’s syndrome. During the 8-month follow-up after surgery, no recurrence of Cushing’s syndrome was found.

Background This study was designed to screen potential biomarkers in plasma cell-free DNA (cfDNA) for predicting the clinical outcome of immune checkpoint inhibitor (ICI)-based therapy in advanced hepatobiliary cancers.Methods Three cohorts including 187 patients with hepatobiliary cancers were recruited from clinical trials at the Peking Union Medical College Hospital. Forty-three patients received combination therapy of programmed cell death protein 1 (PD-1) inhibitor with lenvatinib (ICI cohort 1), 108 patients received ICI-based therapy (ICI cohort 2) and 36 patients received non-ICI therapy (non-ICI cohort). The plasma cfDNA and blood cell DNA mutation profiles were assessed to identify efficacy biomarkers by a cancer gene-targeted next-generation sequencing panel.Results Based on the copy number variations (CNVs) in plasma cfDNA, the CNV risk score model was constructed to predict survival by using the least absolute shrinkage and selection operator Cox regression methods. The results of the two independent ICI-based therapy cohorts showed that patients with lower CNV risk scores had longer overall survival (OS) and progression-free survival (PFS) than those with high CNV risk scores (log-rank p

Statistical shape models (SSMs) have been established as robust anatomical priors for medical image segmentation, registration and anatomy modelling. To construct an SSM which accurately models the inter-subject anatomical variations, it is crucial to compute accurate shape correspondence between the training samples. To achieve this goal, the state-of-the-art shape correspondence computation methods always require tedious segmentation of the training images, while they seldom pay enough attention to the correspondence accuracy of key anatomical landmarks like the bone joints, vessel bifurcations, etc. As a result, the computation of shape correspondence is time-consuming and the correspondence accuracy is imperfect. To solve these problems, this paper proposes a novel shape correspondence computation approach which eliminates the need for image segmentation by registering an organ shape template to the training images. This method allows the human expert to specify key anatomical landmarks in the training images to define the correspondence of the crucial landmarks. An intensity-and-landmark-combined strategy is implemented to utilized both the image intensity and expert landmarks to obtain accurate shape correspondence. This method is evaluated for the construction of head anatomy SSM and spine SSM based on computed tomography (CT) images. The SSMs constructed using the proposed method demonstrates better shape correspondence accuracy than other state-of-the-arts correspondence methods. In particular, this method obtains pixel-level surface correspondence accuracy (1.38 mm) for the skull and sub-pixel level accuracy (0.92 mm) for the spine. The generalisability and specificity of the SSMs constructed using our method are also superior to SSMs constructed using other compared correspondence methods. With this method, we propose a novel approach which takes less human intervention and produces higher quality SSM with better shape modelling accuracy.

In this paper, we study the characteristics of the supercontinuum (SC) induced by the filamentation of two typical vortex beams (i.e., Laguerre-Gaussian (LG) and Bessel-Gaussian (BG) beams) in water. By moving the cuvette filled with water along the laser propagation path, we measure the SC induced by the filamentation of the two vortex beams at different positions in water. The results show that the degree of spectral broadening induced by the filamentation of LG beams hardly changes with the change of position, while for BG beams, the spectral broadening induced by filamentation is weak on both sides and strong in the middle. The value of topological charge (TC) affects the length of the filament formed by BG beams; however, its effect on the spectral broadening induced by the filamentation of LG and BG beams is negligible.

In atmospheric laser communication, a beam is transmitted through an atmospheric channel, and the photocurrent output from a quadrant detector (QD) used as the tracking sensor fluctuates significantly. To ensure uninterrupted communication and to adapt to such fluctuations, in this paper we apply logarithmic amplifiers to process the output signals of a QD. To further improve the measurement accuracy of the spot position, we firstly propose an integral infinite log-ratio algorithm (IILRA) and an integral infinity log-ratio algorithm based on the signal-to-noise ratio (BSNR-IILRA) through analysis of the factors influencing the measurement error considering the signal-to-noise ratio (SNR) parameter. Secondly, the measurement error of the two algorithms under different SNRs and their variations are analyzed. Finally, a spot position detection experiment platform is built to correctly and efficiently verify the two algorithms. The experimental results show that when the SNR is 54.10 dB, the maximum error and root mean square error of the spot position of the IILRA are 0.0054 mm and 0.0039 mm, respectively, which are less than half those of the center approximation algorithm (CAA). When the SNR is 23.88 dB, the maximum error and root mean square error of the spot position of the BSNR-IILRA are 0.0046 mm and 0.0034 mm, respectively, which are one-thirtieth and one-twentieth of the CAA, respectively. The spot position measurement accuracy of the two proposed algorithms is significantly improved compared with the CAA.

Abstract Background PoleStar m660 is a newly developed clinical PET/CT system with time-of-flight (TOF) capability. The aim of this study is to characterize the performance of the new system. Spatial resolution, sensitivity, scatter fraction, and noise equivalent count rate (NECR) were measured on the scanner according to the NEMA NU 2-2012 protocol. The timing resolution was measured using a rotating line source that orbited around the center of field of view (CFOV) at a radius of 20 cm. The image quality phantom was also imaged to quantify the percent contrast, percent background variability, and residual error. The impacts of data acquisition time and bed overlap on the PET image quality were also evaluated using phantom and patient studies. Results The transverse (axial) spatial resolutions were 3.59 mm (3.67), 4.08 mm (4.65), and 5.32 mm (6.48) full width at half maximum (FWHM) at 1 cm, 10 cm, and 20 cm, respectively, off the CFOV. The measured sensitivity was 10.7 cps/kBq at the CFOV and 10.4 cps/kBq at 10 cm off the CFOV. The peak NECR was 216.7 kcps at an activity concentration of 29.1 kBq/ml, and the scatter fraction was 38.2%. An average of 435 ps FWHM timing resolution was measured. For the image quality phantom, the contrast recovery ratios ranged from 33.9 to 76.4%, while the background variability ranged from 4.7 to 2.0%. In the preliminary clinical study, no noticeable difference in the image quality was observed when the scan time for the whole body and brain was reduced to 1 min/bed and 3 min, respectively. The tested 21% bed overlap showed no significant difference in the image quality compared with the default 38% bed overlap setting. Conclusions The physical performances of the PoleStar m660 PET/CT system showed good sensitivity, count rate performance, and timing resolution. The improved performance could help to reduce the acquisition time and bed overlap in the clinical application without detectable compromise in the image quality.

A novel strategy to synthesize copper-based nanoparticles supported on carbon nitride (C3N4) was developed by popping of mixture containing C3N4 and cupric nitrate. Characterizations such as X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD) indicate that the structure of g-C3N4 maintained although a popping process occurred. High resolution transmission electronic microscopy (HRTEM) characterization illustrated that copper-based nanoparticles with diameter of

The pointing accuracy of the Risley prisms beam-steering system mainly depends on the accuracy of the solution method and the impact of the error on the solution. To improve pointing accuracy, the impact of systematic errors on the inverse solution precision is investigated and a correction method is proposed. First, a more accurate error model for Risley prisms is established, and the errors are obtained by the parameter identification method, which corrects the forward solution error. Second, we explain the reason for the error generated by the inverse solution and analyze the variation of the inverse solution error magnitude with the beam deflection angle. A correction method based on pointing-field transformation is proposed. Finally, simulations and experiments are performed to verify the feasibility of the method. Experimental results show that when the beam deflection angle is equal to 0.1°, the maximum and RMS values of the pointing error are reduced by 94.08% and 95.18%, respectively.

Dreams are a part of a person’s life, therefore people may recognize dreams reflection in art works. Dreams as phenomena of a certain physiological state can be filled with plots that are a representation of both a real-life situation and a situation that does not exist in reality. Unreal situations in the dreams of the characters in the prose of A.P. Chekhov are connected with reality. The idea of the character world is formed in works that have oneiric plots, from a combination of real events with events that are unreal. They help to reveal the nature of the character, his attitude to different life situations in real life.

Context: Primary aldosteronism represents an important and common cause of hypertension and is characterized by autonomous aldosterone secretion that results in severe hypertension and hypokalemia. Nonetheless, its manifestations are atypical in some cases, which renders its diagnosis difficult.Case Description: Presented in this report is a Chinese female patient with blood pressure in the high-normal range, and her parathyroid hormone was significantly elevated. Elevated plasma aldosterone concentration plus suppressed plasma rennin activity was suggestive of primary aldosteronism. 68Ga-pentixafor positron emission tomography/computed tomography revealed an aldosterone-producing adenoma, which was globally the second of its kind ever reported so far. Moreover, the tumor was located in an extremely rare area.Conclusions: Patients with primary aldosteronism may present with normal or high-normal blood pressure and a significantly elevated parathyroid hormone. 68Ga-pentixafor PET/CT is potentially a helpful tool for the non-invasive characterization of patients with primary aldosteronism.

To date, many digital atlases of the human head have been developed, but few incorporate the anatomical variations of the population. In this paper, for the first time, we constructed two digital head atlases (DHAs) of Chinese male and female adults, which can be deformed to simulate the inter-subject anatomical variations. The atlases were developed to assist with personalized medical treatment, population based radio magnetic simulation, and medical imaging device design. The statistical shape model approach was used to construct the atlases based on a training set of 65 computed tomography (CT) images (including those of 46 males and 19 females). To evaluate the accuracy of anatomy modeling, we compared the atlas morphometry parameters with the reference values of the Chinese population and observed the reasonable agreement between them. Compared with the existing digital human head atlases, a unique feature of the DHA is the capability of emulating individual head anatomy via model deformation. This feature is validated by registering the DHAs to patient CT images. The registered atlases provide complete anatomy of the target subjects, including the structures that are not clearly visible in the CT images.