Design, Synthesis, and Evaluation of [18F]BIBD-300 as a Positron Emission Tomography Tracer for Poly(ADP-Ribose) Polymerase-1.

Compounds 8a-j were designed to adjust the mode of interaction and lipophilicity of FTT by scaffold hopping and changing the length of the alkoxy groups. Compounds 8a, 8d, 8g, and BIBD-300 were screened for high-affinity PARP-1 through enzyme inhibition assays and are worthy of further evaluation. PET imaging of MCF-7 subcutaneous tumors with moderate expression of PARP-1 showed that compared to [18F]FTT, [18F]8a, [18F]8d, and [18F]8g exhibited greater nonspecific uptake, a lower target-to-nontarget ratio, and severe defluorination, while [18F]BIBD-300 exhibited lower nonspecific uptake and a greater target-to-nontarget ratio. PET imaging of 22Rv1 subcutaneous tumors, which highly express PARP-1, confirmed that the uptake of [18F]BIBD-300 in normal organs, such as the liver, muscle, and bone, was lower than that of [18F]FTT, and the ratio of tumor-to-muscle and tumor-to-liver [18F]BIBD-300 was greater than that of [18F]FTT. The biodistribution results in mice with MCF-7 and 22Rv1 subcutaneous tumors further validated the results of PET imaging. Unlike [18F]FTT, which mainly relies on hepatobiliary clearance, [18F]BIBD-300, which has lower lipophilicity, undergoes a partial shift from hepatobiliary to renal clearance, providing the possibility for [18F]BIBD-300 to indicate liver cancer. The difference in the PET imaging results for [18F]FTT, [18F]BIBD-300, and [18F]8j in 22Rv1 mice and the corresponding molecular docking results further confirmed that subtle structural modifications in lipophilicity greatly optimize the properties of the tracer. Cell uptake experiments also demonstrated that [18F]BIBD-300 has a high affinity for PARP-1. Metabolized and unmetabolized [18F]FTT and [18F]BIBD-300 were detected in the brain, indicating that they could not accurately quantify the amount of PARP-1 in the brain. However, PET imaging of glioma showed that both [18F]FTT and [18F]BIBD-300 could accurately localize both in situ to C6 and U87MG tumors. Based on its potential advantages in the diagnosis of breast cancer, prostate cancer, and glioma, as well as liver cancer, [18F]BIBD-300 is a new option for an excellent PARP-1 tracer.

Typical metabolic pattern of 18F-FDG PET in Anti-NMDAR encephalitis in the acute and subacute phases and its correlation with T2 FLAIR-MRI features.

BACKGROUND/AIMS: Early diagnosis of Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis with non-invasive imaging modalities benefiting is crucial to guarantee prompt treatments decision-making and good prognosis for patients. The present study aimed to explore the correlation of MRI features with brain metabolism characteristics of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) and to describe the metabolic patterns in Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis at acute and subacute phases. Twenty-four patients with anti-NMDAR encephalitis confirmed by serum and/or CSF tests at acute and subacute phases, 9 females and 15 males, with an age range of 6-80 years, were enrolled in this retrospective study as encephalitis group. 18F-FDG PET and MRI findings of all patients were investigated and interpreted with visual analysis. Chi-square test was performed to compare the diagnostic sensitivity between MRI and PET. Independent sample t-test was used to compare the standardized uptake value ratio (SUVR) of each ROI between the encephalitis group and control group, which consisted of 24 healthy volunteers of the same age and gender. RESULTS: There was no statistical difference in the diagnostic sensitivity between FDG PET (23/24, 95.83%) and MRI (18/24, 75.00%) in anti-NMDAR encephalitis patients (P > 0.05). Three categories of abnormalities shown on T2 FLAIR, including shallow of sulci and swelling of brain tissue, increased signal in the sulci, increased signal on brain gray matter or adjacent white matter presented hypermetabolism on PET, excepting increased signal in brain linear structure with hypometabolism of the basal ganglia on PET. We identified 19 brain regions with hypermetabolism and 16 brain regions with hypometabolism that exhibited statistically significant changes in SUVRs between anti-NMDAR encephalitis group and control group (FDR P < 0.05). CONCLUSION: Anteroposterior glucose metabolism gradient (frontal-temporal/parietal-occipital) is proved to be a typical pattern of anti-NMDAR encephalitis at the acute and subacute phases in both visual and statistical testing. Interestingly, the pattern is also commonly found in the anterior and posterior portions of the parietal lobe and cingular cortex, which may be a potential indicator for the diagnosis of this disorder. In addition, MRI is an important and reliable neuroimaging modality to assist in the correct evaluation of activity changes on individual 18F-FDG PET.

Peptidome-wide association analysis of Epstein-Barr virus identifies epitope repertoires associated with nasopharyngeal carcinoma.

Human leukocyte antigen (HLA) molecules are essential for presenting Epstein-Barr virus (EBV) antigens and are closely related to nasopharyngeal carcinoma (NPC). This study aims to systematically investigate the association between HLA-bound EBV peptides and NPC risk through in silico HLA-peptide binding prediction. A total of 455 NPC patients and 463 healthy individuals in NPC endemic areas were recruited, and HLA-target sequencing was performed. HLA-peptide binding prediction for EBV, followed by peptidome-wide logistic regression and motif analysis, was applied. Binding affinity changes for EBV peptides carrying high-risk mutations were analyzed. We found that NPC-associated EBV peptides were significantly enriched in immunogenic proteins and core linkage disequilibrium (LD) proteins related to evolution, especially those binding HLA-A alleles (p = 3.10 × 10-4 for immunogenic proteins and p = 8.10 × 10-5 for core LD proteins related to evolution). These peptides were clustered and showed binding motifs of HLA supertypes, among which supertype A02 presented an NPC-risk effect (padj = 3.77 × 10-4 ) and supertype A03 presented an NPC-protective effect (padj = 4.89 × 10-4 ). Moreover, a decreased binding affinity toward risk HLA supertype A02 was observed for the peptide carrying the NPC-risk mutation BNRF1 V1222I (p = 0.0078), and an increased binding affinity toward protective HLA supertype A03 was observed for the peptide carrying the NPC-risk mutation BALF2 I613V (p = 0.022). This study revealed the distinct preference of EBV peptides for binding HLA supertypes, which may contribute to shaping EBV population structure and be involved in NPC development.

Predictive value of infiltrating tumor border configuration of rectal cancer on MRI.

BACKGROUND: Infiltrating tumor border configuration (iTBC) is assessed by postoperative pathological examination, thus, is not helpful for preoperative treatment strategies. The study aimed to detect iTBC by magnetic resonance imaging (MRI) and evaluate its predictive value. MATERIALS AND METHODS: A total of 153 patients with rectal cancer were retrospectively analyzed. Clinicopathological and MRI data mainly including tumor border configuration (TBC) on MRI, MRI-detected extramural vascular invasion (MEMVI), tumor length, tumor growth pattern, maximal extramural depth, pathology-proven lymph node metastasis (PLN) and pathology-proven extramural vascular invasion (PEMVI) were analyzed. The correlation of MRI factors with PEMVI and PLN was analyzed by univariate and multivariate logistic regression analyses. The nomograms were established based on multivariate logistic regression analysis and were confirmed by Bootstrap self-sampling. The receiver operating characteristic (ROC) curve analysis and area under the curve (AUC) were used to evaluate the diagnostic efficiency. RESULTS: Fifty cases of PEMVI and 48 cases of PLN were found. Forty cases of PEMVI and 34 cases of PLN in 62 cases of iTBC were also found. iTBC, MEMVI and maximal extramural depth were significantly associated with PEMVI and PLN (P < 0.05). iTBC (odds ratio = 3.84 and 3.02) and MEMVI (odds ratio = 7.27 and 3.22) were independent risk factors for PEMVI and PLN. The C-indices of the two nomograms for predicting PEMVI and PLN were 0.863 and 0.752, respectively. The calibration curves and ROC curves of the two nomograms showed that the correlation between the predicted and the actual incidence of PEMVI and PLN was good. The AUCs of iTBC for predicting PEMVI and PLN were 0.793 (95% CI: 0.714-0.872) and 0.721 (95% CI: 0.632-0.810), respectively. The DeLong test showed that the predictive efficiency of the nomogram in predicting PEMVI was better than that of iTBC (P = 0.0009) and MEMVI (P = 0.0095). CONCLUSION: iTBC and MEMVI are risk factors for PEMVI and pelvic lymph node metastasis. The nomograms based on iTBC show a good performance in predicting PEMVI and pelvic lymph node metastasis, possessing a certain clinical reference value. TRIAL REGISTRATION: This study was approved by the Ethics Committee of Beijing Friendship Hospital, and individual consent was waived for this retrospective analysis.

Association between HLA alleles and Epstein-Barr virus Zta-IgA serological status in healthy males from southern China.

BACKGROUND: Nasopharyngeal carcinoma (NPC), an Epstein-Barr virus (EBV) associated cancer, exhibits an extremely high incidence in southern Chinese. Given that human leukocyte antigen (HLA) plays critical roles in antigen presentation and relates to NPC susceptibility, it is speculated that certain HLA variants may affect EBV reactivation, which is a key pathogenic factor of NPC. Therefore, we attempted to identify HLA alleles associated with the indicator of EBV reactivation, Zta-IgA, in healthy males from NPC endemic area. METHODS: HLA alleles of 1078 healthy males in southern China from the 21-RCCP study were imputed using genome-wide single nucleotide polymorphism data. EBV Zta-IgA in blood samples were measured using an enzyme-linked immunosorbent assay. Multiple logistic regression analysis was used to evaluate the effect of HLA allele on Zta-IgA serological status and its potential joint association with smoking. The binding affinity for Zta-peptide was predicted using NetMHCIIpan 4.0. RESULTS: HLA-DRB1*09:01 was found to be associated with a higher risk of Zta-IgA seropositivity (odds ratio = 1.80, 95% confidence interval = 1.32-2.45; p = 1.82 × 10-4 ). Compared with non-smokers without HLA-DRB1*09:01, the effect size increased to 2.19- and 3.70-fold for the light and heavy smokers carrying HLA-DRB1*09:01, respectively. Furthermore, HLA-DRB1*09:01 showed a stronger binding affinity to Zta peptide than other HLA-DRB1 alleles. CONCLUSIONS: Our study highlighted the pivotal role of genetic HLA variants in EBV reactivation and the etiology of NPC. Smokers with HLA-DRB1*09:01 have a significantly higher risk of being Zta-IgA seropositive, which indicates the necessity of smoking cessation in certain high-risk populations and also provide clues for further research on the etiology of NPC.

Post-transplant lymphoproliferative disorder after paediatric liver transplantation.

OBJECTIVE: The purpose of this study was to analyse the clinical and pathological characteristics, treatments and outcomes of post-transplant lymphoproliferative disorder (PTLD) in paediatric liver transplant recipients. METHOD: A retrospective analysis of records from nine paediatric liver transplant recipients with PTLD who were treated at our Liver Transplant Center over the period from June 2013 to August 2018. RESULT: Of these nine patients, seven received liver transplantation in our centre and the remaining two patients at other hospitals. The overall incidence of PTLD in paediatric liver transplant recipients in our centre was 1.4% (7/485). The median onset of PTLD after liver transplantation was 11 months. Three cases were classified as infectious mononucleosis PTLD, one case was plasmacytic hyperplasia PTLD, one case was polymorphic PTLD and two cases were Burkitt lymphoma. One case showed diffuse large B-cell lymphoma and one was classical Hodgkin lymphoma-like PTLD. These patients presented with different clinical manifestations including fever, anaemia, diarrhoea, hypoproteinaemia, enlargement of lymph nodes, hepatosplenomegaly, jaundice, bowel obstruction and even intestinal perforation. Nine patients were positive for EBV-DNA in serum. After diagnosis, immunosuppressants were reduced or discontinued in all cases. Eight patients received anti-CD20 monoclonal antibody (Rituximab) therapy, four cases were treated with a combination of chemotherapy (R-CHOP, ABVD, COPP/ABV) and one case was combined with radiotherapy. Two cases received surgical treatment due to bowel obstruction. Eight of these patients achieved a complete remission and remained healthy when assessed at the time of final follow-up. One patient died as a result of PTLD progression. CONCLUSION: PTLD is one of the most serious and fatal complications after liver transplantation. The definitive diagnosis requires histopathology. Treatment varies and basically includes immunosuppression reduction, anti-CD20 antibody, surgery, radiotherapy and chemotherapy.

Nasopharyngeal Epstein-Barr virus DNA loads in high-risk nasopharyngeal carcinoma families: Familial aggregation and host heritability.

Nasopharyngeal carcinoma (NPC), the most common head and neck cancer, is characterized by distinct geographic distribution and familial aggregation. Multiple risk factors, including host genetics, environmental factor, and EBV infection, have been linked to the development of NPC, particularly in the familial clustering cases. However, the cause of NPC endemicity remains enigmatic due possibly to the complicated interplay between these risk factors. Recently, positive Epstein-Barr virus (EBV) DNA loads at nasopharyngeal (NP) cavity has been found to reflect NPC development and applied in NPC screening. To examine whether the increased NP EBV loads could aggregate in the families and be affected by host genetics and environmental factor, EBV loads were obtained by 510 NP brushing samples from eligible unaffected individuals, who have two or more relatives affected with NPC, in 116 high-risk NPC families. The correlation of relative pairs was estimated using S.A.G.E. (version 6.4, 2016), and host heritability of NP EBV loads was calculated with variance component models using SOLAR (version 8.4.2, 2019). In result, significant correlations of EBV loads were observed between parent-offspring pairs and sibling-sibling pairs (P < .001), but not in distant kin relationship pairs. Interestingly, after excluding the shared environmental factor within families, host genetics contributes significantly to NP EBV loads with a heritability of 56.41% (P = 1.00 × 10-7 ), and its effect was slightly elevated (68.86%, P = 3.40 × 10-6 ) in families with more NPC cases (≥3). These findings indicate that additional host-genetic variants involved in the EBV local NP mucosal behavior may be especially important for the development of NPC.

Elevated expression of the V-ATPase D2 subunit triggers increased energy metabolite levels in KrasG12D -driven cancer cells.

Mutations of the Ras oncogene are frequently detected in human cancers. Among Ras-mediated tumorigenesis, Kras-driven cancers are the most dominant mutation types. Here, we investigated molecular markers related to the Kras mutation, which is involved in energy metabolism in Kras mutant-driven cancer. We first generated a knock-in KrasG12D cell line as a model. The genotype and phenotype of the Kras G12D -driven cells were first confirmed. Dramatically elevated metabolite characterization was observed in Kras G12D -driven cells compared with wild-type cells. Analysis of mitochondrial metabolite-related genes showed that two of the 84 genes in Kras G12D -driven cells differed from control cells by at least twofold. The messenger RNA and protein levels of ATP6V0D2 were significantly upregulated in Kras G12D -driven cells. Knockdown of ATP6V0D2 expression inhibited motility and invasion but did not affect the proliferation of Kras G12D -driven cells. We further investigated ATP6V0D2 expression in tumor tissue microarrays. ATP6V0D2 overexpression was observed in most carcinoma tissues, such as melanoma, pancreas, and kidney. Thus, we suggest that ATP6V0D2, as one of the V-ATPase (vacuolar-type H + -ATPase) subunit isoforms, may be a potential therapeutic target for Kras mutation cancer.

The diagnostic value of 11C-methionine PET in hyperparathyroidism with negative 99mTc-MIBI SPECT: a meta-analysis.

Background 99mTc-sestamibi (MIBI) parathyroid SPECT is generally regarded as the best preoperative localizing method in patients with hyperparathyroidism (HPT). However, 99mTc-MIBI SPECT is false negative in approximately 25% of adenomas. 11C-methionine positron emission tomography (PET) has been used in HPT with negative 99mTc-MIBI SPECT scan results. Purpose To systematically review and conduct a meta-analysis of published data on the performance of 11C-methionine PET in patients with HPT with negative 99mTc-MIBI SPECT. Material and Methods A comprehensive review of the literature was performed. Pooled sensitivity and specificity of 11C-methionine PET in patients with HPT and a negative 99mTc-MIBI SPECT was calculated on a per-patient basis using receiver-operating characteristic (ROC) methodology. Results Nine studies that met all inclusion and exclusion criteria were included into our meta-analysis, comprising a total sample size of 137 patients. Pooled sensitivity and specificity of 11C-methionine PET in patients with HPT with negative or inconclusive 99mTc-MIBI SPECT scans was 86% and 86%, respectively. The area under the ROC curve was 0.87. Conclusion By merit of the high overall sensitivity, specificity, and accuracy, 11C-methionine PET can potentially complement the diagnostic workup of patients with HPT and negative or inconclusive 99mTc-MIBI SPECT. 11C-methionine PET appears to be a promising diagnostic modality in complicated cases with HPT.

The value of anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid PET/CT in the diagnosis of recurrent prostate carcinoma: a meta-analysis.

BACKGROUND: Anti-1-amino-3-[18F]fluorocyclobutane-1-carboxylic acid (anti-3-18F-FACBC) positron emission tomography/computed tomography (PET/CT), 11 C-choline PET/CT, 111In-capromab pendetide, and T2-weighted magnetic resonance imaging (MRI) have been used for detecting prostate carcinoma relapse. PURPOSE: To systematically review and perform a meta-analysis of published data regarding the performance of 18F-FACBC PET/CT in the diagnosis of recurrent prostate carcinoma. MATERIAL AND METHODS: A comprehensive review of the literature regarding the role of 18F-FACBC PET/CT in the diagnosis of recurrent prostate carcinoma was performed. Pooled sensitivity, specificity, and the area under the receiver-operating characteristic of 18F-FACBC PET/CT in the diagnosis of recurrent prostate carcinoma were calculated based on the included studies. RESULTS: Six studies comprising 251 patients, suspicious of prostate carcinoma recurrence, were included in this meta-analysis. 18F-FACBC PET/CT had an 87% pooled sensitivity, 66% pooled specificity, 0.93 the area under the receiver-operating characteristic curve on a per patient-based analysis in detecting prostate carcinoma recurrence. CONCLUSION: 18F-FACBC PET/CT was a non-invasive, metabolic imaging technique in the diagnosis of prostate carcinoma relapse.

The accuracy of V/Q SPECT in the diagnosis of pulmonary embolism: a meta-analysis.

BACKGROUND: Ventilation perfusion single photon emission computed tomography (V/Q SPECT) and CT pulmonary angiography have all been used in the diagnosis of acute PE. Previous studies have shown higher sensitivity and specificity and a marked decrease in the non-diagnostic rate of V/Q SPECT than planar scan. PURPOSE: To systematically review and perform a meta-analysis of published data on the performance of V/Q SPECT in the diagnosis of acute PE. MATERIAL AND METHODS: A comprehensive computer search was conducted on literature published through 31 December 2013 in an effort to find relevant articles on the diagnostic performance of V/Q SPECT in the diagnosis of PE patients. Pooled sensitivity, specificity, negative likelihood ratio (LR), and positive LR, the area under the receiver-operating characteristic (ROC) curve of V/Q SPECT in the diagnosis of PE patients were calculated. RESULTS: Nine studies, comprising a total sample size of 3454 patients, were included in our meta-analysis. The pooled sensitivity, specificity of V/Q SPECT in the diagnosis of acute PE patients, calculated on a per-patient-based analysis, was 96% (95% confidence interval [CI], 95-97%), 97% (95% CI, 96-98%). The pooled negative LR, positive LR of V/Q SPECT in acute PE patients was 0.06 (range, 0.02-0.19) and 16.64 (range, 9.78-31.54). The area under the ROC curve of V/Q SPECT in the diagnosis of acute PE patients was 0.99 on a per-patient-based analysis. CONCLUSION: V/Q SPECT is an accurate method in acute PE patients with high sensitivity and high specificity in the diagnosis of PE.

Value of dual-phase (99m)Tc-sestamibi scintigraphy with neck and thoracic SPECT/CT in secondary hyperparathyroidism.

OBJECTIVE: Surgical intervention in the form of parathyroidectomy is generally considered only for severe secondary hyperparathyroidism (sHPT). However, correct location of the parathyroid glands before parathyroidectomy is a challenge. The purpose of this study was to compare the diagnostic value of early and delayed phase (99m)Tc-sestamibi SPECT/CT in the detection of parathyroid tissue to guide operative treatment of patients with sHPT. SUBJECTS AND METHODS: Eighty patients with sHPT who were undergoing hemodialysis were evaluated preoperatively with dual-phase (99m)Tc-sestamibi SPECT/CT parathyroid scintigraphy to locate parathyroid tissue before parathyroidectomy. The scintigraphic results were classified as positive or negative. The accuracy of (99m)Tc sestamibi early and delayed phase SPECT/CT scintigraphy was determined. RESULTS: Early phase (99m)Tc-sestamibi SPECT/CT depicted 3.57 parathyroid glands (PTGs) and delayed phase (99m)Tc-sestamibi SPECT/CT depicted 3.55 PTGs per study. The specificity of both early and delayed phase (99m)Tc-sestamibi SPECT/CT in detecting PTGs was 100%. The (99m)Tc-sestamibi SPECT/CT images of 7 of 80 patients showed positive findings in the delayed phase and negative findings in the early phase. The (99m)Tc-sestamibi SPECT/CT images of 6 of 80 patients showed positive findings in the early phase and negative findings in the delayed phase. CONCLUSION: The results of our study indicate that both early and delayed phase (99m)Tc-sestamibi SPECT/CT should be performed in the preoperative evaluation of hemodialysis patients with sHPT due to chronic kidney disease. Performance of both early and delayed phase (99m)Tc-sestamibi SPECT/CT did not increase the radiation dose compared with the use of only the early or the delayed phase.

Diagnostic role of Gallium-68 DOTATOC and Gallium-68 DOTATATE PET in patients with neuroendocrine tumors: a meta-analysis.

BACKGROUND: Gallium-68 somatostatin receptor positron emission tomography (PET) has been used in the diagnosis of neuroendocrine tumors (NETs). The compounds often used in molecular imaging of NETs with PET are 68Ga-DOTATOC, 68Ga-DOTATATE, and 68Ga-DOTANOC. There is varying affinity to different somatostatin receptors. PURPOSE: To systematically review and perform a meta-analysis of published data regarding the diagnostic role of 68Ga-DOTATOC and 68Ga-DOTATATE PET in the diagnosis of NETs. MATERIAL AND METHODS: A comprehensive literature search of studies published through 30 April 2013 regarding 68Ga-DOTATOC and 68Ga-DOTATATE PET in the diagnosis of NETs was performed using the PubMed/MEDLINE, Embase, and Scopus databases. Pooled sensitivity and specificity of 68Ga-DOTATOC and 68Ga-DOTATATE PET in the diagnosis of NETs were calculated. The area under the receiver-operating characteristic (ROC) curve was calculated to measure the accuracy of 68Ga-DOTATOC and 68Ga-DOTATATE PET in the diagnosis of NETs. RESULTS: Ten studies comprising 416 patients with NETs were included in this meta-analysis. The pooled sensitivity of 68Ga-DOTATOC and 68Ga-DOTATATE PET in the diagnosis of NETs calculated on a per-patient-based analysis was 93% (95% confidence interval [CI] 89-96%) and 96% (95% CI 91-99%). The pooled specificity of 68Ga-DOTATOC and 68Ga-DOTATATE PET in diagnosing NETs was 85% (95% CI 74-93%) and 100% (95% CI 82-100%). The area under the ROC curve of 68Ga-DOTATOC and 68Ga-DOTATATE PET was 0.96 and 0.98, respectively, on a per-patient-based analysis. CONCLUSION: The molecular imaging agents 68Ga-DOTATOC and 68Ga-DOTATATE demonstrated high sensitivity and specificity in the diagnosis of NETs on PET scan. Although both are accurate tools in the diagnosis of NETs, 68Ga-DOTATATE PET may be more sensitive and specific than 68Ga-DOTATOC PET scan.

T2-weighted Imaging Features of the Fetal Thymus in the Middle and Late Pregnancy: A Post-mortem Study based on Magnetic Resonance Imaging.

BACKGROUND: Fat-suppressed (FS) T2-weighed turbo spin-echo (TSE) sequence was used to detect the signal of the thymus and the characteristics of the thymus location, measure the two-dimensional diameter at specific levels, and analyze the association with gestational weeks. METHODS: This study involved 51 fetal specimens. Post-mortem MRI scanning was implemented with a 3.0-T MRI system. T2-weighted imaging (T2WI) features of the thymus in fetuses were quantitatively investigated with DICOM images. Statistical analysis was done with the Chi-Square test, oneway ANOVA, and Student's t-test. RESULTS: There was heterogeneity in the morphology of the fetal thymus. FS T2-weighted TSE sequence clearly exhibited the microstructure of the fetal thymus. The thymus extensively showed a lobulated appearance. The central signal is much higher than the peripheral signal in each lobule. In addition, FS-T2WI images can clearly show the interlobular septum, which is filled with fluid and presents a linear high signal. The signal intensity of fetal thymus increased with gestational weeks. The diameter measured in a particular plane was highly correlated with gestational week. CONCLUSION: FS T2-weighted TSE sequence provides high-resolution images of the fetal thymus. The change in signal intensity, location, and two-dimensional diameter in a specific plane can be used as a research direction for the fetal thymus.

Machine learning and new insights for breast cancer diagnosis.

Breast cancer (BC) is the most prominent form of cancer among females all over the world. The current methods of BC detection include X-ray mammography, ultrasound, computed tomography, magnetic resonance imaging, positron emission tomography and breast thermographic techniques. More recently, machine learning (ML) tools have been increasingly employed in diagnostic medicine for its high efficiency in detection and intervention. The subsequent imaging features and mathematical analyses can then be used to generate ML models, which stratify, differentiate and detect benign and malignant breast lesions. Given its marked advantages, radiomics is a frequently used tool in recent research and clinics. Artificial neural networks and deep learning (DL) are novel forms of ML that evaluate data using computer simulation of the human brain. DL directly processes unstructured information, such as images, sounds and language, and performs precise clinical image stratification, medical record analyses and tumour diagnosis. Herein, this review thoroughly summarizes prior investigations on the application of medical images for the detection and intervention of BC using radiomics, namely DL and ML. The aim was to provide guidance to scientists regarding the use of artificial intelligence and ML in research and the clinic.

18F-Labeled PET Tracers Specific for Adenosine A2A Receptor: Design, Synthesis, and Biological Evaluation.

By modifying the structures of targeted A2AR antagonists and tracers, novel compounds 3, 7a, 9, 12c, and BIBD-399 were designed and synthesized. In vitro inhibition experiments demonstrated that 3, 12c, and BIBD-399 have high affinity for A2AR. [18F]3 and [18F]BIBD-399 were successfully synthesized. In terms of biological distribution, the brain uptake of [18F]MNI-444 exhibits greater than that of [18F]3 and [18F]BIBD-399. PET imaging shows that [18F]3 is off-target in the brain, while [18F]BIBD-399 and [18F]MNI-444 can be specifically imaged in regions with high A2AR expression. Differently, [18F]BIBD-399 could quickly reach equilibrium in the targeted region within 10 min after administration, while [18F]MNI-444 shows a slowly increasing trend within 2 h of administration. [18F]BIBD-399 is mainly metabolized by the liver and kidney, and there is no obvious defluorination in vivo. Additional in vitro autoradiography showed that the striatal signals of [18F]BIBD-399 and [18F]MNI-444 were inhibited by the A2AR antagonist SCH442416 but not by the A1R antagonist DPCPX, demonstrating the high A2AR binding specificity of [18F]BIBD-399. Molecular docking further confirms the high affinity of MNI-444 and BIBD-399 for A2AR. Further tMCAo imaging showed that [18F]BIBD-399 can sensitively distinguish between infarcted and noninfarcted sides, a capability not observed with [18F]MNI-444. Given its pharmacokinetic properties and the ability to identify lesion regions, [18F]BIBD-399 has potential advantages in monitoring A2AR changes, meriting further clinical investigation.

Cortical metabolic characteristics of anti-leucine-rich glioma-inactivated 1 antibody encephalitis based on 18F-FDG PET.

Purpose: A general glucose metabolism pattern is observed in patients with anti-leucine-rich glioma-inactivated 1 (LGI1) antibody encephalitis; however, it is unclear whether further subregional metabolic differences exist. Therefore, the present study aimed to conduct an in-depth exploration of the features of glucose metabolism within specific brain areas using 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET). Materials and methods: This retrospective study enrolled thirteen patients confirmed with LGI1 antibody encephalitis who were admitted to Beijing Tiantan Hospital from June 2021 to September 2022. All patients underwent 18F-FDG PET before initiating clinical treatment. Changes in glucose metabolism in specific brain areas were analyzed using Cortex ID software. The laterality of 18F-FDG uptake was assessed, and differences in specific brain areas were compared using paired t-tests. Results: Significant metabolic changes in at least one brain region in 11 out of 13 patients (84.6%) were revealed by semi-quantitative analysis (z-score > 2). A bilateral decrease in the 18F-FDG metabolic pattern was revealed in almost all brain regions of interest; in contrast, a hypermetabolic pattern was observed in the medial temporal region, with mean z-scores of 1.75 ± 3.27 and 2.36 ± 5.90 on the left and right sides, respectively (p = 0.497). In the prefrontal and temporal lobes, 18F-FDG metabolism was significantly lower in the lateral region than in the medial region on both sides. For the cingulate cortex, significant hypometabolism was also observed in the posterior part compared to the anterior counterpart on both the left (z-score: -1.20 ± 1.93 vs. -0.42 ± 1.18, respectively; p = 0.047) and right (z-score: -1.56 ± 1.96 vs. -0.33 ± 1.63, respectively; p = 0.001) sides. However, a significant difference in regional metabolism was observed only on the left side (p = 0.041). Conclusion: An asymmetric 18F-FDG metabolic pattern exists in patients with anti-LGI1 encephalitis. Meanwhile, varied regional metabolic differences were revealed bilaterally in specific cerebral areas, which could be associated with the clinical manifestations.

Brown adipose tissue: distribution and influencing factors on FDG PET/CT scan.

Brown adipose tissue (BAT) functions as a thermogenic organ by producing heat to maintain body temperature in many mammals, especially in the young. BAT is generally found in deep cervical, supraclavicular, interscapular, and paravertebral regions, as well as areas near large vessels. If not recognized, BAT activity can considerably interfere with 18F-fluorodeoxyglucose position emission tomography (PET)/computed tomography (CT) image interpretation. BAT activation can be influenced by several factors and reduced by different methods. In this paper, we review BAT distribution and factors influencing BAT activity on FDG PET/CT scan. The purpose of this review is to enhance the recognition of pediatric-related physician of BAT on FDG PET/CT scan.

18F-DOPA positron emission tomography/computed tomography application in congenital hyperinsulinism.

Congenital hyperinsulinism (CHI) during infancy is characterized by inappropriate insulin secretion resulting in persistent hypoglycemia. This can lead to irreversible severe neurological damage in the infant. There are two main histologic subtypes: diffuse and focal, both of which may require different surgical strategies. It is very important to differentiate focal leisons from diffuse leisons. However, the differentiation of diffuse leisons from focal leisons is challenging. Affected pancreatic areas utilize dihydroxyphenylalanine (DOPA) at a higher rate than normal pancreatic tissues; thus, labeling of L-DOPA with fluorine-18 (18F-DOPA) allows functional mapping of hyperinsulinism using positron emission tomography/computed tomography (PET/CT). In this article, we reviewed the 18F-DOPA PET/CT application in CHI. The aim of this review is to enhance the recognition of 18F-DOPA PET/CT application in the diagnosis of CHI.

Development and validation of a polygenic hazard score to predict prognosis and adjuvant chemotherapy benefit in early-stage non-small cell lung cancer.

Background: It remains controversial who would benefit from adjuvant chemotherapy (ACT) in patients with early-stage non-small cell lung cancer (NSCLC). We aim to construct a polygenic hazard score (PHS) to predict prognosis and ACT benefit among NSCLC patients. Methods: We conducted a retrospective study including 1,395 stage I-II NSCLC patients. We performed a genome-wide association study (GWAS) on overall survival (OS) in patients treated with ACT (SYSUCC ACT set, n=404), and then developed a PHS using LASSO Cox regression in a random subset (training, n=202) and tested it in the remaining set (test, n=202). The PHS was further validated in two independent datasets (SYSUCC surgery set, n=624; PLCO cohort, n=367). Results: The GWAS-derived PHS consisting of 37 single-nucleotide polymorphisms (SNPs) was constructed to classify patients into high and low PHS groups. For patients treated with ACT, those with low PHS had better clinical outcomes than high PHS (test set: HR =0.21, P<0.001; PLCO ACT set: HR =0.33, P=0.260). Similar results were found in the extended validation cohorts including patients with or without ACT (SYSUCC: HR =0.48, P<0.001; PLCO: HR =0.60, P=0.033). Within subgroup analysis by treatment or clinical factors, we further observed consistent results for the prognostic value of the PHS. Notably, ACT significantly improved OS in stage II patients with low PHS (HR =0.26, P<0.001), while there was no ACT survival benefit among patients with high PHS (HR =0.97, P=0.860). Conclusions: The PHS improved prognostic stratification and could help identify patients who were most likely to benefit from ACT in early-stage NSCLC.