Biodegradation of combined pollutants of polyethylene terephthalate and phthalate esters by esterase-integrated Pseudomonas sp. JY-Q with surface-co-displayed PETase and MHETase.

The waste pollution problem caused by polyethylene terephthalate (PET) plastics poses a huge threat to the environment and human health. As plasticizers, Phthalate esters (PAEs) are widely used in PET production and become combined pollutants with PET. Synthetic biology make it possible to construct engineered cells for microbial degradation of combined pollutants of PET and PAEs. PET hydroxylase (PETase) and monohydroxyethyl terephthalate hydroxylase (MHETase) isolated from Ideonella sakaiensis 201-F6 exhibit the capability to depolymerize PET. However, PET cannot enter cells, thus enzymatic degradation or cell surface displaying technology of PET hydrolase are the potential strategies. In this study, Pseudomonas sp. JY-Q was selected as a chassis strain, which exhibits robust stress tolerance. First, a truncated endogenous outer membrane protein cOmpA and its variant Signal (OprF)-cOmpA were selected as anchor motifs for exogenous protein to display on the cell surface. These anchor motifs were fused at the N-terminal of PET hydrolase and MHETase and transformed into Pseudomonas sp. JY-Q, the mutant strains successfully display the enzymes on cell surface, after verification by green fluorescent protein labeling and indirect immunofluorescence assay. The resultant strains also showed the catalytic activity of co-displaying PETase and MHETase for PET biodegradation. Then, the cell surface displaying PET degradation module was introduced to a JY-Q strain which genome was integrated with PAEs degrading enzymes and exhibited PAEs degradation ability. The resultant strain JY-Q-R1-R4-SFM-TPH have the ability of degradation PET and PAEs simultaneously. This study provided a promising strain resource for PET and PAEs pollution control.

A challenging diagnosis of prostate cancer seeding in the perineal needle-tract after transperineal biopsy: is PET-CT the imaging of choice?

Perineal seeding is an extremely rare complication after prostate biopsy. We found a perineal localization of prostatic adenocarcinoma 5 years after the transperineal biopsy in a patient with metastatic castration resistant prostate cancer. The tumor was identified by a18F-Fluorocholin positron emission tomography-computed tomography (18F-FCH PET-CT) performed after a sudden rise of PSA levels during androgen deprivation therapy and after a negative CT scan. This case report underscores the challenge one may encounter in detecting perineal prostate cancer metastasis after a biopsy when using traditional imaging with CT scan alone or MRI, and the added diagnostic value of PET-CT imaging.

A novel simple suture method for establishing an orthotopic pancreatic cancer mouse model: a comparative study with two conventional methods.

OBJECTIVE: This study aims to evaluate the efficacy of a novel simple suture method in establishing an optimal animal model for preclinical research in pancreatic cancer. METHODS: To establish a novel simple suture method, the tumor fragment was placed on the tail of the pancreas and securely wrapped into the pancreas, and compared with two conventional methods: the cell injection method and the tumor fragment embedding method. Subsequently, emission tomography/computed tomography scanning, gross anatomy observation, hematoxylin and eosin staining, and immunohistochemistry staining were performed to assess the effectiveness of these methods. RESULTS: The emission tomography/computed tomography scanning and anatomical examinations confirmed the successful construction of orthotopic pancreatic cancer models using all three methods. Histopathological analysis of the orthotopic masses and metastatic lesions revealed malignant transformation with tumor infiltration into normal tissue. Comparative analysis demonstrated that the cell injection method was easy to perform but resulted in poor uniformity of tumor size and had high costs. The tumor fragment embedding method exhibited excellent uniformity of tumor size, with the highest tumor growth rates and a greater pancreatic impairment. In contrast, the novel simple suture method featured a relatively simple surgical procedure, slower growth rates, good uniformity of tumor size, and minimal pancreatic impairment. CONCLUSION: The novel simple suture method is the optimal protocol for establishing an orthotopic pancreatic cancer mouse model, providing a robust foundation for preclinical studies on pancreatic cancer.

Isolated spermatic cord metastasis of prostate cancer after radiotherapy detected with 18F-PSMA PET/CT: a case report and literature review.

We report the case of a 65 year-old male with prostate cancer previously treated with external beam radiotherapy and 2 years of androgen deprivation therapy. His nadir PSA reached undetectable level but gradually increased to 0.89 ng/dL. 18F-PSMA PET/CT demonstrated a PSMA-avid lesion at left spermatic cord. Left groin exploration revealed an 8 mm left vas deferens mass. Mass excision was performed and pathology result showed prostatic adenocarcinoma. The metastatic route is unknown but the possible routes are intraluminal route via ejaculatory duct, hematogenous route and lymphatic route. This case also highlights the role of 18F-PSMA PET/CT to detect a recurrent lesion at an atypical site in biochemical failure patients even at the low PSA level.

Exploring AMR and virulence in Klebsiella pneumoniae isolated from humans and pet animals: A complement of phenotype by WGS-derived profiles in a One Health study in Egypt.

Klebsiella pneumoniae is a ubiquitous nosocomial pathogen associated with various types of infections in hospitalized patients and different animal species. In the current study, 49 Klebsiella strains isolated from humans, dogs, and cats were investigated using NGS technology. MALDI-TOF failed to identify newly discovered K. variicola and K. quasipneumoniae isolates correctly. MLST analysis revealed different sequence types among K. pneumoniae isolates, and the most frequent STs were ST29, ST219, and ST37. Three ST23 that are generally known as hypervirulent type were identified but they lacked major discriminatory determinants for hypervirulent K. pneumoniae (hvKp). K. pneumoniae isolates showed high diversity, and several isolates from humans and animals were assigned to the same ST and were almost identical. Isolates from humans exhibited more pronounced resistance patterns compared to the animal isolates. High levels of resistance were observed for piperacillin, trimethoprim/sulfamethoxazole, and cephalosporins, and resistance to carbapenem compounds was only found in isolates of human origin. Three strains of human origin were extensively drug-resistant (XDR). A diverse range of resistance genes primarily confer resistance to beta-lactams., phenicol/quinolone, aminoglycoside, macrolide, sulfonamides, and fosfomycin were identified in silico. However, there were inconsistencies between the phenotypic characterization of isolates and the set of resistance genes detected in silico in this set of Klebsiella isolates. Further research using a larger number of isolates from various sources is necessary to fully comprehend the relationship between the presence of antimicrobial resistance determinants and phenotypic data. It is also necessary to monitor the spread of K. pneumoniae from a One Health perspective in Egypt.

Neurostructural changes in schizophrenia and treatment-resistance: a narrative review.

Schizophrenia is a complex disorder characterized by multiple neurochemical abnormalities and structural changes in the brain. These abnormalities may begin before recognizable clinical symptoms appear and continue as a dynamic process throughout the illness. Recent advances in imaging techniques have significantly enriched our comprehension of these structural alterations, particularly focusing on gray and white matter irregularities and prefrontal, temporal, and cingulate cortex alterations. Some of the changes suggest treatment resistance to antipsychotic medications, while treatment nonadherence and relapses may further exacerbate structural abnormalities. This narrative review aims to discuss the literature about alterations and deficits within the brain, which could improve the understanding of schizophrenia and how to interpret neurostructural changes.

Impaired mitochondrial function in bipolar disorder and alcohol use disorder: a case study using 18F-BCPP-EF PET imaging of mitochondrial Complex I.

Background: With bipolar disorder (BD) having a lifetime prevalence of 4.4% and a significant portion of patients being chronically burdened by symptoms, there has been an increased focus on uncovering new targets for intervention in BD. One area that has shown early promise is the mitochondrial hypothesis. However, at the time of publication no studies have utilized positron emission tomography (PET) imaging to assess mitochondrial function in the setting of BD. Case Presentation: Our participant is a 58 year-old male with a past medical history notable for alcohol use disorder and BD (unspecified type) who underwent PET imaging with the mitochondrial complex I PET ligand 18F-BCPP-EF. The resulting images demonstrated significant overlap between areas of dysfunction identified with the 18F-BCPP-EF PET ligand and prior functional magnetic resonance imaging (MRI) techniques in the setting of BD. That overlap was seen in both affective and cognitive circuits, with mitochondrial dysfunction in the fronto-limbic, ventral affective, and dorsal cognitive circuits showing particularly significant differences. Conclusions: Despite mounting evidence implicating mitochondria in BD, this study represents the first PET imaging study to investigate this mechanistic connection. There were key limitations in the form of comorbid alcohol use disorder, limited statistical power inherent to a case study, no sex matched controls, and the absence of a comprehensive psychiatric history. However, even with these limitations in mind, the significant overlap between dysfunction previously demonstrated on functional MRI and this imaging provides compelling preliminary evidence that strengthens the mechanistic link between mitochondrial dysfunction and BD.

Immuno-PET Imaging of EGFR with 64Cu-NOTA Panitumumab in Subcutaneous and Metastatic Nonsmall Cell Lung Cancer Xenografts.

Objective: About 65-90% of nonsmall cell lung cancer (NSCLC) express the epithelial growth factor receptor (EGFR) as a transmembrane protein that is activated by binding of specific ligands, including epidermal growth factor and transforming growth factor α (TGFα). Identifying EGFR as an oncogene has led to the development of anticancer therapeutics directed against EGFR, including the full-length human IgG2 monoclonal antibody panitumumab. The main goal of the present study was to investigate 64Cu-labeled panitumumab with immuno-PET in subcutaneous and metastatic EGFR-positive NSCLC xenografts. Methods: Bifunctional chelating agent 2-S-(4-isothiocyanatobenzyl)-1,4,7-triazacyclo-nonane-1,4,7-triacetic acid (NOTA-NCS) was attached to panitumumab. The number of chelators per panitumumab was determined using matrix-assisted laser desorption/ionization (MALDI) mass spectroscopy. The incorporation efficiency of 64Cu into NOTA-panitumumab was measured by using radio-TLC. EGFR-expressing epithelial-like H1299-luc+ NSCLC cells were used for in vitro and in vivo experiments. Cell uptake of [64Cu]Cu-NOTA-panitumumab was measured in the presence and absence of panitumumab. Subcutaneous and metastatic H1299-luc tumor models were grown in male NSG mice. The presence of tumors at lung and metastatic sites was analyzed by [18F]FLT PET. Immuno-PET with [64Cu]Cu-NOTA-panitumumab was performed as static PET imaging at 2, 24, and 48 h postinjection in both tumor models. Proof-of-target was confirmed by blocking experiments with panitumumab. Detailed ex vivo biodistribution experiments were performed in both animal tumor models to confirm biodistribution profiles obtained by immuno-PET imaging. Results: MALDI analysis confirmed the attachment of ∼1.5 NOTA per antibody. Radiolabeling efficiency with [64Cu]CuCl2 was 93.8 ± 5.7% and a molar activity of 0.65 MBq/µg. Cellular uptake studies with [64Cu]Cu-NOTA-panitumumab in H1299 cells demonstrated increasing uptake over time, reaching 29.1 ± 2.9% radioactivity(Bq)/mg protein (n = 3) and plateauing at 45 min. Addition of 25 µg of panitumumab reduced radioligand uptake to 1.22 ± 0.06% radioactivity/mg protein (n = 3). PET imaging revealed high uptake of [64Cu]Cu-NOTA-panitumumab in subcutaneous tumors: Standardized uptake values (SUV)mean reached 4.70 ± 0.42 and 5.37 ± 0.40 (n = 5) after 24 and 48 h postinjection, respectively. Administration of 1 mg panitumumab reduced tumor uptake significantly to 1.94 ± 0.22 and 1.66 ± 0.08 (n = 4; p < 0.001). In the metastatic model, the following SUVmean were analyzed from liver and lung lesions: 5.55 ± 0.34 and 6.28 ± 0.46 (both n = 23 lesions from 6 mice) after 24 and 48 h postinjection, which was also significantly reduced to 2.53 ± 0.39 and 2.31 ± 0.15 (both n = 16 lesions from 4 mice; p < 0.001) after injection of 1 mg panitumumab. Detailed ex vivo biodistribution confirmed immuno-PET analysis in both models. Panitumumab reduced radioactivity uptake into subcutaneous tumors from 11.01 ± 0.72 (n = 4) to 3.67 ± 0.33% ID/g (n = 5; p < 0.001), and in metastatic liver lesions from 29.44 ± 8.14 (n = 4) to 8.35 ± 1.30% ID/g (n = 5; p < 0.001), respectively. Conclusions: [64Cu]Cu-NOTA-panitumumab was successfully used for immuno-PET imaging of EGFR-expressing subcutaneous and metastatic NSCLC tumors. This result represents the basis for developing radiotheranostics for targeting EGFR in cancers and for selecting the right patients for the right treatment at the right time.

Evaluating early response assessment in extranodal natural killer/T-cell lymphoma by analyzing ΔSUVlbm between baseline and interim 18F-FDG PET/CT scans.

To determine the optimal variation in SUVlbm via 18F-FDG PET/CT imaging between the baseline and interim stages, and assess early response among patients with extranodal natural killer/T-cell lymphoma (ENKTCL) of 5-DS score ≥ 4, 20 patients after four cycles of chemotherapy were retrospectively enrolled and received re-biopsy targeting PET-positive residual masses. The optimal cutoff value for evaluating early response assessment was 66.75% for ΔSUVlbm%, with the area under curve of 0.985. All patients with a 5-DS score of 4 exhibited negative results upon re-biopsy. During follow-up, the median PFS of patients characterized by ΔSUVlbm% ≥66.75% and <66.75% were unreached and 10 months, respectively. Utilizing ΔSUVlbm% between baseline and interim 18F-FDG PET/CT scans can effectively identify a subset of patients who were visually analyzed as false positives(5-DS ≥ 4), which was confirmed by interim biopsy results, thus serving as a crucial indicator for early assessment of treatment outcomes in patients with ENKTCL.

[68Ga]Ga-LNC1007 versus 2-[18F]FDG in the evaluation of patients with metastatic differentiated thyroid cancer: a head-to-head comparative study.

PURPOSE: This head-to-head comparison study aimed to compare the performance of [68Ga]Ga-FAPI-RGD (LNC1007) and 2-[18F]FDG PET/CT in the evaluation of patients with metastatic differentiated thyroid cancer (mDTC). METHODS: Ten unexplained hyperthyroglobulinemia (UHTg) patients and 20 patients with definite metastatic lesions of thyroid cancer (DmDTC) were enrolled in the study. All patients underwent both [68Ga]Ga-LNC1007 and 2-[18F]FDG PET/CT within 1 week. The final diagnosis was based on histopathological results and a comprehensive evaluation of laboratory tests and multimodal imaging characteristics. RESULTS: In patients with UHTg, [68Ga]Ga-LNC1007 PET/CT detected more metastatic lymph nodes (LNs) (17 vs. 15, P = 0.317) and lung lesions (2 vs. 0) than 2-[18F]FDG. In patients with DmDTC, [68Ga]Ga-LNC1007 PET/CT also detected more true positive lesions than 2-[18F]FDG (Total: 133 vs. 103, LN: 20 vs. 15, lung: 18 vs. 10, bone: 87 vs.73). [68Ga]Ga-LNC1007 PET/CT demonstrated significantly higher SUVmax (Total: 6.30 vs. 3.84, LN: 8.28 vs. 4.82, Lung: 3.31 vs. 1.49, Bone: 5.73 vs. 3.87, all P < 0.05) and TBR (Total: 6.92 vs. 4.93, LN: 6.48 vs. 4.16, Lung: 5.16 vs. 2.57, Bone: 7.22 vs. 5.41, all P < 0.05) in true positive lesions compared to 2-[18F]FDG. Specifically, the sensitivity of [68Ga]Ga-LNC1007 PET/CT was higher than that of 2-[18F]FDG in detecting lung and bone metastases (94.7% vs. 52.6% and 100% vs. 83.9%, all P < 0.05). [68Ga]Ga-LNC1007 PET/CT exhibited better specificity and accuracy in diagnosing LNs (96.9% vs. 66.7% and 96.3% vs. 68.5%, all P < 0.05). However, the specificity of [68Ga]Ga-LNC1007 for bone metastasis was inferior to 2-[18F]FDG (15.4% vs. 88.5%, P < 0.05). CONCLUSION: Compared with 2-[18F]FDG, [68Ga]Ga-LNC1007 PET/CT could detect more metastatic lesions, with higher SUVmax and TBR, in patients with mDTC. [68Ga]Ga-LNC1007 had better accuracy in the diagnosis of LN and lung metastasis. Trial registration ClinicalTrials.gov NCT05515783. Registered 01 May 2022. URL of registry https://classic. CLINICALTRIALS: gov/ct2/show/NCT05515783.

Using a novel PSMA-PET and PSA-based model to enhance the diagnostic accuracy for clinically significant prostate cancer and avoid unnecessary biopsy in men with PI-RADS ≤ 3 MRI.

INTRODUCTION: The diagnostic evaluation of men with suspected prostate cancer (PCa) yet inconclusive MRI (PI-RADS ≤ 3) presents a common clinical challenge. [68Ga]Ga-labelled prostate-specific membrane antigen ([68Ga]Ga-PSMA) positron emission tomography/computed tomography (PET/CT) has shown promise in identifying clinically significant PCa (csPCa). We aim to establish a diagnostic model incorporating PSMA-PET to enhance the diagnostic process of csPCa in PI-RADS ≤ 3 men. MATERIALS AND METHODS: This study retrospective included 151 men with clinical suspicion of PCa and PI-RADS ≤ 3 MRI. All men underwent [68Ga]Ga-PSMA PET/CT scans and ultrasound/MRI/PET fusion-guided biopsies. csPCa was defined as Grade Group ≥ 2. PRIMARY-scores from PSMA-PET scans were evaluated. A diagnostic model incorporating PSMA-PET and prostate-specific antigen (PSA)-derived parameters was developed. The discriminative performance and clinical utility were compared with conventional methods. Internal validation was conducted using a fivefold cross-validation with 1000 iterations. RESULTS: In this PI-RADS ≤ 3 cohort, areas-under-the-curve (AUCs) for detecting csPCa were 0.796 (95%CI, 0.738-0.853), 0.851 (95%CI, 0.783-0.918) and 0.806 (95%CI, 0.742-0.870) for PRIMARY-score, SUVmax and routine clinical PSMA-PET assessment, respectively. The diagnostic model comprising PRIMARY-score, SUVmax and serum free PSA/total PSA (fPSA/tPSA) achieved a significantly higher AUC of 0.906 (95%CI, 0.851-0.961) compared to strategies based on PRIMARY-score or SUVmax (P < 0.05) and markedly superior to conventional strategies typically based on PSA density (P < 0.001). The average fivefold cross-validated AUC with 1000 iterations was 0.878 (95%CI, 0.820-0.954). Theoretically, using a threshold of 21.6%, the model could have prevented 78% of unnecessary biopsies while missing only 7.8% of csPCa cases in this cohort. CONCLUSIONS: A novel diagnostic model incorporating PSMA-PET derived metrics-PRIMARY-score and SUVmax-along with serum fPSA/tPSA, has been developed and validated. The integrated model may assist clinical decision-making with enhanced diagnostic accuracy over the individual conventional metrics. It has great potential to reduce unnecessary biopsies for men with PI-RADS ≤ 3 MRI results and warrants further prospective and external evaluations.

Persistent dysfunctions of brain metabolic connectivity in long-covid with cognitive symptoms.

PURPOSE: Our study examines brain metabolic connectivity in SARS-CoV-2 survivors during the acute-subacute and chronic phases, aiming to elucidate the mechanisms underlying the persistence of neurological symptoms in long-COVID patients. METHODS: We perfomed a cross-sectional study including 44 patients (pts) with neurological symptoms who underwent FDG-PET scans, and classified to timing infection as follows: acute (7 pts), subacute (17 pts), long-term (20 pts) phases. Interregional correlation analysis (IRCA) and ROI-based IRCA were applied on FDG-PET data to extract metabolic connectivity in resting state networks (ADMN, PDMN, EXN, ATTN, LIN, ASN) of neuro-COVID pts in acute/subacute and long-term groups compared with healthy controls (HCs). Univariate approach was used to investigate metabolic alterations from the acute to sub-acute and long-term phase. RESULTS: The acute/subacute phase was characterized by hyperconnectivity in EXN and ATTN networks; the same networks showed hypoconnectivity in the chronic phase. EXN and ATTN hypoconnectivity was consistent with clinical findings in long-COVID patients, e.g. altered performances in neuropsychological tests of executive and attention domains. The ASN and LIN presented hyperconnectivity in acute/subacute phase and normalized in long-term phase. The ADMN and PDMN presented a preseverved connectivity. Univariate analysis showed hypometabolism in fronto-insular cortex in acute phase, which reduced in sub-acute phase and disappeared in long-term phase. CONCLUSION: A compensatory EXN and ATTN hyperconnectivity was found in the acute/subacute phase and hypoconnectivity in long-term. Hypoconnectivity and absence of hypometabolism suggest that connectivity derangement in frontal networks could be related to protraction of neurological symptoms in long-term COVID patients.

Metastasis of Colon Cancer to the Accessory Spleen: A Case Report.

Distant metastasis to the spleen is extremely rare. To the best of our knowledge, metastasis to the accessory spleen based on pathological findings has only been reported in four patients in the English literature, including one each of ovarian cancer, transitional cell carcinoma, breast cancer, and uterine carcinosarcoma after surgery. Furthermore, among these reported cases, only two reports (one each of transitional cell carcinoma and uterine carcinosarcoma) presented imaging findings. In this study, we report a case of colon cancer metastasis to the accessory spleen without involvement of the spleen in a 58-year-old male patient, providing imaging findings. This case emphasized the importance of considering the possibility of metastasis to the accessory spleen in patients with malignancy.

Transcatheter Aortic Valve-in-Valve Implantation in a Patient Due to the Degeneratation of the Biointegral Valve Conduit as a Result of Previous Infectious Endocarditis.

Graft infection, fistula, and mediastinitis are reported among the serious cardiovascular complications after a Bentall procedure. Surgery associated with antimicrobial treatment is usually recommended but not easily feasible in most cases. In this report, we describe a case of successful valve-in-valve (ViV) transcatheter aortic valve replacement (TAVR) in a patient with a degenerated bioconduit from a previously healed infectious endocarditis (IE). The TAVR procedure has been demonstrated to be a therapeutic option in selected cases with a previous history of IE who have been fully treated with antimicrobial therapy and who present a low risk of local re-infection and are deemed at prohibitive or high risk for surgical replacement. Data on TAVR on a bioconduit after a Bentall procedure are scarce. The present case underlines that a long follow-up and individualized treatment could improve the prognosis in patients with a history of prosthetic valve and aortic graft infection and severe valve dysfunction who cannot undergo surgical treatment. The 18F-labeled fluoro-2-deoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) result could be successfully employed in the decision algorithm. Long-term antibiotic treatment, which could be lifelong in some instances, could be a reasonable choice when the risk of recurrence is associated with the risk for the patient's life.

Investigating the feasibility of 18F-flortaucipir PET imaging in the antemortem diagnosis of primary age-related tauopathy (PART): An observational imaging-pathological study.

INTRODUCTION: Primary age-related tauopathy (PART) is characterized by neurofibrillary tangles and minimal ß-amyloid deposition, diagnosed postmortem. This study investigates 18F-flortaucipir (FTP) PET imaging for antemortem PART diagnosis. METHODS: We analyzed FTP PET scans from 50 autopsy-confirmed PART and 13 control subjects. Temporal lobe uptake was assessed both qualitatively and quantitatively. Demographic and clinicopathological characteristics and voxel-level uptake using SPM12 were compared between FTP-positive and FTP-negative cases. Intra-reader reproducibility was evaluated with Krippendorff's alpha. RESULTS: Minimal/mild and moderate FTP uptake was seen in 32% of PART cases and 62% of controls, primarily in the left inferior temporal lobe. No demographic or clinicopathological differences were found between FTP-positive and FTP-negative cases. High intra-reader reproducibility (α = 0.83) was noted. DISCUSSION: FTP PET imaging did not show a specific uptake pattern for PART diagnosis, indicating that in vivo PART identification using FTP PET is challenging. Similar uptake in controls suggests non-specific uptake in PART. HIGHLIGHTS: 18F-flortaucipir (FTP) PET scans were analyzed for diagnosing PART antemortem. 32% of PART cases had minimal/mild FTP uptake in the left inferior temporal lobe. Similar to PART FTP uptake was found in 62% of control subjects. No specific uptake pattern was found, challenging in vivo PART diagnosis.

Diagnostic accuracy and treatment benefit of PET/CT in staging of colorectal cancer compared to conventional imaging.

BACKGROUND: Until recently the use of positron emission tomography (PET) CT for staging in colorectal cancer (CRC) has been limited to the detection of distant metastasis in advanced disease. But with the introduction of neoadjuvant treatments in CRC, accurate pre-treatment staging has become more relevant. AIMS: The aim of the study was to assess the staging accuracy for nodal and distant metastasis of PET/CT compared to computed tomography (CT) alone in CRC. Secondary endpoints were overall survival (OS) and cost of CT compared to PET/CT. METHODS: A retrospective analysis of 539 cases with CRC staged with PET/CT and or CT between 2015 and 2021 in a Swiss tertiary referral center was performed. In 471 patients for nodal staging and 479 for staging of distant metastasis the clinical stage of both modalities was compared with pathological stage. RESULTS: The distribution of UICC stages (n = 479) was as follows: Stage I 62 cases (12.9 %), Stage II 127 cases (26.5 %), Stage III 199 cases (41.5 %), Stage IV 91 cases (19.0 %). CT alone compared to PET was able to predict nodal involvement with a sensitivity of 55.2 % (95%CI 5.7-59.7 %) and 66.7 % (95%CI 62.4-70.9 %), respectively. The specificity was 67.0 % (95%CI 62.8-71.3 %) for CT and 63.6 % (95%CI 59.3-68.0 %) for PET. The positive predictive value was 49.5 % for CT vs. 51.8 % for PET. The sensitivity of metastasis detection was 53.6 % (95%CI 49.1-58.1 %) for CT and 82.5 % (95%CI 79.1-85.9 %) for PET. CONCLUSIONS: PET/CT showed higher sensitivity in the detection of lymph node involvement and metastases in CRC patients compared to CT alone.

Explainable AI for automated respiratory misalignment detection in PET/CT imaging.

PURPOSE: Positron emission tomography (PET) image quality can be affected by artifacts emanating from PET, CT, or artifacts due to misalignment between PET and CT images. Automated detection of misalignment artifacts can be helpful both in data curation and in facilitating clinical workflow. This study aimed to develop an explainable machine learning approach to detect misalignment artifacts in PET/CT imaging. Approach. This study included 1216 PET/CT images. All images were visualized and images with respiratory misalignment artifact (RMA) detected. Using previously trained models, four organs including the lungs, liver, spleen, and heart were delineated on PET and CT images separately. Data were randomly split into cross-validation (80%) and test set (20%), then two segmentations performed on PET and CT images were compared and the comparison metrics used as predictors for a random forest framework in a 10-fold scheme on cross-validation data. The trained models were tested on 20% test set data. The model's performance was calculated in terms of specificity, sensitivity, F1-Score and area under the curve (AUC). Main Results. Sensitivity, specificity, and AUC of 0.82, 0.85, and 0.91 were achieved in ten-fold data split. F1_score, sensitivity, specificity, and AUC of 84.5 vs 82.3, 83.9 vs 83.8, 87.7 vs 83.5, and 93.2 vs 90.1 were achieved for cross-validation vs test set, respectively. The liver and lung were the most important organs selected after feature selection. Significance. We developed an automated pipeline to segment four organs from PET and CT images separately and used the match between these segmentations to decide about the presence of misalignment artifact. This methodology may follow the same logic as a reader detecting misalignment through comparing the contours of organs on PET and CT images. The proposed method can be used to clean large datasets or integrated into a clinical scanner to indicate artifactual cases.

Improved Localization of Insulinomas Using 68Ga-NODAGA-Exendin-4 PET/CT.

Precise anatomic localization of insulinomas is crucial for surgical treatment. Current routine noninvasive imaging techniques, including CT, MRI, and 68Ga-DOTA-somatostatin analog (DOTA-SSA) PET/CT, have limited sensitivity. Endoscopic ultrasound is highly sensitive but invasive. In this prospective multicenter study, we compared the diagnostic accuracy of 68Ga-NODAGA-exendin-4 (exendin) PET/CT with all routine imaging procedures for the localization of insulinomas. Methods: Sixty-nine adults with biochemically proven adult endogenous hyperinsulinemic hypoglycemia underwent exendin PET/CT and current routine imaging. Images were evaluated in a clinical reading and in an expert reading. Image quality was determined by quantitative analysis. Results: Based on clinical readings, the accuracy of exendin PET/CT (94.4%; 95% CI, 84.6%-98.8%) was greater than that of DOTA-SSA PET/CT (64.8%; 95% CI, 50.6%-77.3%), contrast-enhanced CT/contrast-enhanced diffusion-weighted imaging-MRI (83.3%; 95% CI, 70.7%-92.1%), and endoscopic ultrasound (82.8%; 95% CI, 64.1%-94.1%). In 13% of patients, a correct diagnosis was only reached after exendin PET/CT. Interobserver agreement between readings was higher for exendin PET/CT than for DOTA-SSA PET/CT and contrast-enhanced CT/contrast-enhanced diffusion-weighted imaging-MRI (Cohen κ, 1.0 vs. 0.5 and 0.55). Exendin PET/CT provided a higher insulinoma-to-background ratio (15.3 ± 6.7 vs. 5.2 ± 3.0) and contrast-to-noise ratio (22.6 ± 11.1 vs. 5.1 ± 3.7) than did DOTA-SSA PET/CT. Conclusion: This study demonstrates the superiority of exendin PET/CT in a unique prospective comparison to all current routine imaging modalities for preoperative localization of benign insulinomas, providing the level of evidence needed for clinical implementation.

Imaging Glucose Metabolism and Dopaminergic Dysfunction in Sheep (Ovis aries) Brain Using Positron Emission Tomography Imaging Reveals Abnormalities in OVT73 Huntington's Disease Sheep.

Huntington's disease (HD) is a neurodegenerative disease that causes cognitive, movement, behavioral, and sleep disturbances, which over time result in progressive disability and eventually death. Clinical translation of novel therapeutics and imaging probes could be accelerated by additional testing in well-characterized large animal models of HD. The major goal of our preliminary cross-sectional study is to demonstrate the feasibility and utility of the unique transgenic sheep model of HD (OVT73) in positron emission tomography (PET) imaging. PET imaging studies were performed in healthy merino sheep (6 year old, n = 3) and OVT73 HD sheep (5.5 year old, n = 3, and 11 year old, n = 3). Region-of-interest and brain atlas labels were defined for regional analyses by using a sheep brain template. [18F]fluorodeoxyglucose ([18F]FDG) was employed to compare the regional brain glucose metabolism and variations in FDG uptake between control and HD sheep. We also used [18F]fluoro-3,4-dihydroxyphenylalanine ([18F]FDOPA) to compare the extent of striatal dysfunction and evaluated the binding potential (BPND) in key brain regions between the groups. Compared with healthy controls and 11 year old HD sheep, the 5.5 year old HD sheep exhibited significantly increased [18F]FDG uptake in several cortical and subcortical brain regions (P < 0.05-0.01). No difference in [18F]FDG uptake was observed between healthy controls and 11 year old HD sheep. Analysis of the [18F]FDOPA BPND parametric maps revealed clusters of reduced binding potential in the 5.5 year old and 11 year old HD sheep compared to the 6 year old control sheep. In this first-of-its-kind study, we showed the usefulness and validity of HD sheep model in imaging cerebral glucose metabolism and dopamine uptake using PET imaging. The identification of discrete patterns of metabolic abnormality using [18F]FDG and decline of [18F]FDOPA uptake may provide a useful means of quantifying early HD-related changes in these models, particularly in the transition from presymptomatic to early symptomatic phases of HD.

Imaging in psoriatic arthritis: established methods and emerging techniques.

Psoriatic arthritis (PsA) is a heterogeneous, chronic, inflammatory musculoskeletal disease that can lead to peripheral and axial damage and loss of function. A clear difference between PsA and other forms of inflammatory arthritis is the different forms of bone remodeling seen in PSA which incorporates not only increased bone resorption with bone erosions, osteolysis, and loss of bone mineral density but also increased bone formation with periostitis, syndesmophytes, enthesiophytes, and ankylosis. PsA, if diagnosed late, will lead to significant structural damage, the most severe form of which is known as arthritis mutilans, and loss of physical function. Imaging plays a crucial role in diagnosing and monitoring both peripheral and axial conditions associated with PsA. Radiography is currently the main modality used to monitor structural damage in PsA though commonly used scoring systems do not include bony proliferation as a criterion. Besides, radiography is limited in determining the presence and cause of periarticular soft tissue thickening, which may arise from tendinosis, tenosynovitis, synovial proliferation, bursitis, or enthesitis. Recently, much more attention has been paid to determining the imaging characteristics of PsA, which enables more precise identification of disease and severity assessment. Newer imaging technologies also enable variations in normal bone microstructure to be distinguished from disease-related abnormality. This review discusses the current state of innovative imaging modalities in PsA, specifically concentrating on their roles in PsA diagnosis and treatment, improving the early detection of PsA, and identifying patients with skin psoriasis at risk of developing psoriatic arthritis.