Association of synaptic density and cognitive performance in temporal lobe epilepsy: Humans and animals PET imaging study with [18F]SynVesT-1.

AIM: Cognitive impairment is a common comorbidity in individuals with temporal lobe epilepsy (TLE), yet the underlying mechanisms remain unknown. This study explored the putative association between in vivo synaptic loss and cognitive outcomes in TLE patients by PET imaging of synaptic vesicle glycoprotein 2A (SV2A). METHODS: We enrolled 16 TLE patients and 10 cognitively normal controls. All participants underwent SV2A PET imaging using [18F]SynVesT-1 and cognitive assessment. Lithium chloride-pilocarpine-induced rats with status epilepticus (n = 20) and controls (n = 6) rats received levetiracetam (LEV, specifically binds to SV2A), valproic acid (VPA), or saline for 14 days. Then, synaptic density was quantified by [18F]SynVesT-1 micro-PET/CT. The novel object recognition and Morris water maze tests evaluated TLE-related cognitive function. SV2A expression was examined and confirmed by immunohistochemistry. RESULTS: Temporal lobe epilepsy patients showed significantly reduced synaptic density in hippocampus, which was associated with cognitive performance. In the rat model of TLE, the expression of SV2A and synaptic density decreased consistently in a wider range of brain regions, including the entorhinal cortex, insula, hippocampus, amygdala, thalamus, and cortex. We treated TLE animal models with LEV or VPA to explore whether synaptic loss contributes to cognitive deficits. It was found that LEV significantly exerted protective effects against brain synaptic deficits and cognitive impairment. CONCLUSION: This is the first study to link synaptic loss to cognitive deficits in TLE, suggesting [18F]SynVesT-1 PET could be a promising biomarker for monitoring synaptic loss and cognitive dysfunction. LEV might help reverse synaptic deficits and ameliorate learning and memory impairments in TLE patients.

Individual cerebellar metabolic connectome in patients with MTLE and NTLE associated with surgical prognosis.

PURPOSE: This study aimed to comprehensively explore the different metabolic connectivity topological changes in MTLE and NTLE, as well as their association with surgical outcomes. METHODS: This study enrolled a cohort of patients with intractable MTLE and NTLE. Each individual's metabolic connectome, as determined by Kullback-Leibler divergence similarity estimation for the [18F]FDG PET image, was employed to conduct a comprehensive analysis of the cerebral metabolic network. Alterations in network connectivity were assessed by extracting and evaluating the strength of edge and weighted connectivity. By utilizing these two connectivity strength metrics with the cerebellum, we explored the network properties of connectivity and its association with prognosis in surgical patients. RESULTS: Both MTLE and NTLE patients exhibited substantial alterations in the connectivity of the metabolic network at the edge and nodal levels (p < 0.01, FDR corrected). The key disparity between MTLE and NTLE was observed in the cerebellum. In MTLE, there was a predominance of increased connectivity strength in the cerebellum. Whereas, a decrease in cerebellar connectivity was identified in NTLE. It was found that in MTLE, higher edge connectivity and weighted connectivity strength in the contralateral cerebellar hemisphere correlated with improved surgical outcomes. Conversely, in NTLE, a higher edge metabolic connectivity strength in the ipsilateral cerebellar hemisphere suggested a worse surgical prognosis. CONCLUSION: The cerebellum exhibits distinct topological characteristics in the metabolic networks between MTLE and NTLE. The hyper- or hypo-metabolic connectivity in the cerebellum may be a prognostic biomarker of surgical prognosis, which might aid in therapeutic decision-making for TLE individuals.

Clinical translation of a novel FAPI dimer [68Ga]Ga-LNC1013.

Fibroblast activation protein (FAP) has emerged as a highly promising target for cancer diagnostic imaging and targeted radionuclide therapy. To exploit the therapeutic potential of suitably radiolabeled FAP inhibitors (FAPIs), this study presents the design and synthesis of a series of FAPI dimers to increase tumor uptake and retention. Preclinical evaluation and a pilot clinical PET imaging study were conducted to screen the lead compound with the potential for radionuclide therapy. METHODS: Three new FAPI dimers were synthesized by linking two quinoline-based FAPIs with different spacers. The in vitro binding affinity and preclinical small animal PET imaging of the compounds were compared with their monomeric counterparts, FAPI-04 and FAPI-46. The lead compound, [68Ga]Ga -LNC1013, was then evaluated in a pilot clinical PET imaging study involving seven patients with gastrointestinal cancer. RESULTS: The three newly synthesized FAPI homodimers had high binding affinity and specificity in vitro and in vivo. Small animal PET imaging and biodistribution studies showed that [68Ga]Ga-LNC1013 had persistent tumor retention for at least 4 h, also higher uptake than the other two dimers and the monomer counterparts, making it the lead compound to enter clinical investigation. In the pilot clinical PET imaging study, seven patients were enrolled. The effective dose of [68Ga]Ga-LNC1013 was 8.24E-03 mSv/MBq. The human biodistribution of [68Ga]Ga-LNC1013 demonstrated prominent tumor uptake and good tumor-to-background contrast. [68Ga]Ga-LNC1013 PET imaging showed potential in capturing primary and metastatic lesions and outperforming 18F-FDG PET in detecting pancreatic and esophageal cancers. The SUVmax for lesions with [68Ga]Ga-FAPI-46 decreased over time, whereas [68Ga]Ga-LNC1013 exhibited persistently high tumor uptake from 1 to 4 h post-injection. CONCLUSION: Dimerization is an effective strategy to produce FAPI derivatives with favorable tumor uptake, long tumor retention, and imaging contrast over its monomeric counterpart. We demonstrated that [68Ga]Ga-LNC1013, the lead compound without any piperazine moiety, had superior diagnostic potential over [68Ga]Ga-FAPI-46 and 18F-FDG, suggesting the future potential of LNC1013 for radioligand therapy of FAP-positive cancers.

[18F]SynVesT-1 and [18F]FDG quantitative PET imaging in the presurgical evaluation of MRI-negative children with focal cortical dysplasia type II.

PURPOSE: MRI-negative children with focal cortical dysplasia type II (FCD II) are one of the most challenging cases in surgical epilepsy management. We aimed to utilize quantitative positron emission tomography (QPET) analysis to complement [18F]SynVesT-1 and [18F]FDG PET imaging and facilitate the localization of epileptogenic foci in pediatric MRI-negative FCD II patients. METHODS: We prospectively enrolled 17 MRI-negative children with FCD II who underwent [18F]SynVesT-1 and [18F]FDG PET before surgical resection. The QPET scans were analyzed using statistical parametric mapping (SPM) with respect to healthy controls. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) of [18F]SynVesT-1 PET, [18F]FDG PET, [18F]SynVesT-1 QPET, and [18F]FDG QPET in the localization of epileptogenic foci were assessed. Additionally, we developed a multivariate prediction model based on dual trace PET/QPET assessment. RESULTS: The AUC values of [18F]FDG PET and [18F]SynVesT-1 PET were 0.861 (sensitivity = 94.1%, specificity = 78.2%, PPV = 38.1%, NPV = 98.9%) and 0.908 (sensitivity = 82.4%, specificity = 99.2%, PPV = 93.3%, NPV = 97.5%), respectively. [18F]FDG QPET showed lower sensitivity (76.5%) and NPV (96.6%) but higher specificity (95.0%) and PPV (68.4%) than visual assessment, while [18F]SynVesT-1 QPET exhibited higher sensitivity (94.1%) and NPV (99.1%) but lower specificity (97.5%) and PPV (84.2%). The multivariate prediction model had the highest AUC value (AUC = 0.996, sensitivity = 100.0%, specificity = 96.6%, PPV = 81.0%, NPV = 100%). CONCLUSIONS: The multivariate prediction model based on [18F]SynVesT-1 and [18F]FDG PET/QPET assessments holds promise in noninvasively identifying epileptogenic regions in MRI-negative children with FCD II. Furthermore, the combination of visual assessment and QPET may improve the sensitivity and specificity of diagnostic tests in localizing epileptogenic foci and achieving a preferable surgical outcome in MRI-negative FCD II.

Relationship of single and co-exposure of per-and polyfluoroalkyl substances and their alternatives with uric acid: A community-based study in China.

Numerous studies have suggested per-and polyfluoroalkyl substances (PFASs) are related to uric acid levels, but evidence related to PFAS alternatives is limited. Moreover, the effect of the combined exposure to PFASs and their alternatives on uric acid has not been reported. Hence, we conducted a cross-sectional study involving 1312 adults in Guangzhou, China. Generalized linear regression model was adopted to explore the effect of single PFAS exposure on serum uric acid levels. Further, multi-pollutant models such as Bayesian kernel machine regression, weighted quantile sum, and quantile G-computation were employed to investigate the combined association of PFASs and alternatives with serum uric acid levels. We performed molecular docking to understand the potential interaction of PFAS with Organic Anion Transporters (OATs), involved in the secretion of uric acid. Per log serum 6:2 Cl-PFESA and PFOA increases were accompanied with an increase of serum uric acid with statistical significance (for 6:2 Cl-PFESA: beta: 0.19 ng/mL, 95% CI 0.11-0.26 and for PFOA: beta: 0.43 ng/mL, 95% CI 0.34-0.52). The associations were strongest among overweight and elderly. Multi-pollutant models also revealed a positive association. These positive associations may be PFASs can competitively combine with OAT1 and OAT3, leading to the increase of serum uric acid.

[18F]FDG PET metabolic patterns in mesial temporal lobe epilepsy with different pathological types.

OBJECTIVES: To investigate [18F]FDG PET patterns of mesial temporal lobe epilepsy (MTLE) patients with distinct pathologic types and provide possible guidance for predicting long-term prognoses of patients undergoing epilepsy surgery. METHODS: This was a retrospective review of MTLE patients who underwent anterior temporal lobectomy between 2016 and 2021. Patients were classified as having chronic inflammation and gliosis (gliosis, n = 44), hippocampal sclerosis (HS, n = 43), or focal cortical dysplasia plus HS (FCD-HS, n = 13) based on the postoperative pathological diagnosis. Metabolic patterns and the severity of metabolic abnormalities were investigated among MTLE patients and healthy controls (HCs). The standardized uptake value (SUV), SUV ratio (SUVr), and asymmetry index (AI) of regions of interest were applied to evaluate the severity of metabolic abnormalities. Imaging processing was performed with statistical parametric mapping (SPM12). RESULTS: With a mean follow-up of 2.8 years, the seizure freedom (Engel class IA) rates of gliosis, HS, and FCD-HS were 54.55%, 62.79%, and 69.23%, respectively. The patients in the gliosis group presented a metabolic pattern with a larger involvement of extratemporal areas, including the ipsilateral insula. SUV, SUVr, and AI in ROIs were decreased for patients in all three MTLE groups compared with those of HCs, but the differences among all three MTLE groups were not significant. CONCLUSIONS: MTLE patients with isolated gliosis had the worst prognosis and hypometabolism in the insula, but the degree of metabolic decrease did not differ from the other two groups. Hypometabolic regions should be prioritized for [18F]FDG PET presurgical evaluation rather than [18F]FDG uptake values. CLINICAL RELEVANCE STATEMENT: This study proposes guidance for optimizing the operation scheme in patients with refractory MTLE and emphasizes the potential of molecular neuroimaging with PET using selected tracers to predict the postsurgical histology of patients with refractory MTLE epilepsy. KEY POINTS: • MTLE patients with gliosis had poor surgical outcomes and showed a distinct pattern of decreased metabolism in the ipsilateral insula. • In the preoperative assessment of MTLE, it is recommended to prioritize the evaluation of glucose hypometabolism areas over [18F]FDG uptake values. • The degree of glucose hypometabolism in the epileptogenic focus was not associated with the surgical outcomes of MTLE.

Efficacy of indocyanine green fluorescence-guided inguinal lymph node dissection for penile cancer: a randomised trial.

OBJECTIVES: To investigate the safety and efficacy of indocyanine green (ICG) fluorescence-guided inguinal lymph node dissection (ILND) in patients with penile cancer. PATIENTS AND METHODS: A prospective, single-blind, randomised controlled clinical trial (ChiCTR2100044584) was performed among patients with penile caner who underwent bilateral modified ILND at four centres in China between 1 April 2021 and 30 June 2022. Patients aged 18-80 years and diagnosed with squamous cell carcinomas were included. Each enrolled patient was randomly assigned to either ICG fluorescence-guided ILND by a laparoscopic or robot-assisted approach in one groin, with non-ICG fluorescence-guided ILND in the other groin acting as a control. The primary outcome was the number of retrieved ILNs. Secondary outcomes included complications according to the Clavien-Dindo classification and the ILN non-compliance (inadequate removal of ILNs) rate. RESULTS: A total of 45 patients were included in the intention-to-treat (ITT) analysis, and the 42 who completed the entire study were included in the per protocol (PP) analysis. There were no ICG-related complications in any of the patients. The results of the ITT and PP analyses indicated that the total number of unilateral ILNs retrieved was higher on the ICG side than on the non-ICG side (mean 13 vs 9 ILNs, difference 4 ILNs [95% CI 2.7-4.4], P = 0.007), and the number of unilateral deep and superficial ILNs was higher on the ICG side. Furthermore, the LN non-compliance rate was lower on the ICG side than on the non-ICG side. Additionally, there was no significant difference in local complications in the groins between the two sides (P > 0.05). CONCLUSION: An ICG fluorescence-guided ILND was safe for patients with penile cancer. This procedure can improve the number of ILNs retrieved and reduce the LN non-compliance rate without increased complications. ICG fluorescence-guided ILND is beneficial and recommended for selected patients with penile cancer.

Primary Adenosquamous Carcinoma of the Prostate With Multiple Heterogenic Metastases Demonstrated on 68 Ga-PSMA and 18 F-FDG PET/CT Imaging.

ABSTRACT: A 54-year-old man presented with a 2-month history of urination disturbances. Serum prostate-specific antigen level was 4.96 ng/mL, and a possibility of benign prostate hyperplasia was raised by outside medical CT. Histopathology revealed adenosquamous carcinoma. Staging workup showed large areas of high PSMA uptake and focal intense hypermetabolism in the prostate, multiple lymphatics, bone, and pulmonary heterogenic metastases on 68 Ga-PSMA and 18 F-FDG PET/CT imaging.

[68Ga]Ga-AUNP-12 PET imaging to assess the PD-L1 status in preclinical and first-in-human study.

PURPOSE: PD-L1 PET imaging, as a non-invasive procedure, can perform a real-time, dynamic and quantitative analysis of PD-L1 expression at tumor sites. In this study, we developed a novel peptide-based PET tracer, [68 Ga]Ga-AUNP-12, for preclinical and first-of-its-kind imaging of PD-L1 expression in patients. METHODS: Radiosynthesis of [68 Ga]Ga-AUNP-12 was conducted. Assays for cellular uptake and binding were conducted on the PANC02, CT26, and B16F10 cell lines. Preclinical models were used to investigate its biodistribution, imaging capacity, and pharmacokinetics. Furthermore, interferon-γ (IFN-γ) was used for development of an animal model with high PD-L1 expression for targeted PET imaging and efficacy evaluation of PD-L1 blocking therapy. In healthy volunteers and cancer patients, the PD-L1 imaging, radiation dosimetry, safety, and biodistribution were further evaluated. RESULTS: In vitro and in vivo animal studies showed that [68 Ga]Ga-AUNP-12 PET imaging displayed a high specificity in evaluating PD-L1 expression. The radiochemical yield of [68 Ga]Ga-AUNP-12 was 71.7 ± 8.2%. Additionally, its molar activity and radiochemical purity were satisfactory. The B16F10 tumor was visualized with the tumor uptake of 6.86 ± 0.71% ID/g and tumor-to-muscle ratio of 6.83 ± 0.36 at 60 min after [68 Ga]Ga-AUNP-12 injection. Furthermore, [68 Ga]Ga-AUNP-12 PET imaging could sensitively detect the PD-L1 dynamic changes in CT26 tumor xenograft models regulated by IFN-γ treatment, and correspondingly can effectively guide immunotherapy. Regarding radiation dosimetry, [68 Ga]Ga-AUNP-12 is safe for human use. The first human study found that [68 Ga]Ga-AUNP-12 can be rapidly cleared from blood and other nonspecific organs through the kidney excretion, leading to form a clear imaging contrast in the clinical framework. The specificity of [68 Ga]Ga-AUNP-12 was validated and tumor uptake strongly correlated with the high PD-L1 expression in patients with lung adenocarcinoma and oesophageal squamous cell carcinoma (OSCC). CONCLUSION: [68 Ga]Ga-AUNP-12 was successfully developed as a PD-L1-specific PET imaging tracer in preclinical and first-in-human studies.

Two-way adjustable double-knots intrascleral fixation and single sclerotomy looping technique: a novel minimal invasive adjustable intraocular lens fixation technique.

BACKGROUND: IOL fixation without capsular support presents challenges for surgeons. Although innovative techniques were developed to address subluxated IOLs, adjustable IOL fixation methods are seldom reported. We introduce a novel two-way adjustable double-knots intrascleral fixation combined with single sclerotomy looping technique for fixing intraocular lenses (IOL) or IOL-capsular bags. METHODS: A bent 30-gauge needle threaded with 8 - 0 polypropylene was introduced into the eye. A gripping forceps assisted the haptic looping. Two overhand knots were made with 8 - 0 polypropylene thread. The knots were incarcerated into a scleral tunnel made by a 30-gauge needle, with two ends of the thread left at each side of the tunnel. The IOL was adjusted to the premium position with adequate tension by pulling either end of the threads. The study included 19 eyes with aphakia, subluxated IOL-capsular bags, or subluxated crystalline lenses. The mean followed up period was 18.9 ± 7.1 months with evaluations of uncorrected visual acuity (UCVA), intraocular pressure, slit-lamp examination, and swept-source optical coherence tomography of the anterior segment. RESULTS: UCVA increased from 1.28 ± 0.74 at baseline to 0.44 ± 0.51 (logMAR) at final visit (P < 0.001). All IOLs were fixed well-centered. The mean IOL tilt was 3.5°±1.1°. Postoperative complications included transient IOP elevation (15.8%), hypotony (10.5%), and cystoid edema (5.3%) which resolved within 4 weeks. CONCLUSIONS: We presented a novel adjustable technique for IOL fixation, which stabilize IOLs by using an intrascleral double-knots structure. This technique minimized surgical manipulations by using a single sclerotomy looping technique without large conjunctival dissection and scleral flap creation. The technique offers a reliable and optimal IOL positioning and improved visual outcomes in patients undergoing scleral fixed IOL implantation.

68Ga-PSMA PET/CT-based multivariate model for highly accurate and noninvasive diagnosis of clinically significant prostate cancer in the PSA gray zone.

BACKGROUND: The prostate-specific antigen (PSA) has been widely used in screening and early diagnosis of prostate cancer (PCa). However, in the PSA grey zone of 4-10 ng/ml, the sensitivity and specificity for diagnosing PCa are limited, resulting in considerable number of unnecessary and invasive prostate biopsies, which may lead to potential overdiagnosis and overtreatment. We aimed to predict clinically significant PCa (CSPCa) by combining the maximal standardized uptake value (SUVmax) based on 68Ga­PSMA PET/CT and clinical indicators in men with gray zone PSA levels. METHODS: 81 patients with suspected PCa based on increased serum total PSA (TPSA) levels of 4 - 10 ng/mL who underwent transrectal ultrasound/magnetic resonance imaging (MRI)/PET fusion-guided biopsy were enrolled. Among them, patients confirmed by histopathology were divided into the CSPCa group and the non-CSPCa group, and data on PSA concentration, prostate volume (PV), PSA density (PSAD), free PSA (FPSA)/TPSA, Prostate Imaging-Reporting and Data System version 2.1 (PI-RADS v2.1) score, 68Ga-PSMA PET/CT imaging evaluation results and SUVmax were compared. Multivariate logistic regression analysis was performed to identify the independent predictors for CSPCa, thereby establishing a predictive model based on SUVmax that was evaluated by analyzing the receiver operating characteristic (ROC) curve and decision curve analysis. RESULTS: Compared to non-CSPCa, CSPCa patients had smaller PVs (median, 31.40 mL), lower FPSA/TPSA (median, 0.12), larger PSADs (median, 0.21 ng/mL2) and higher PI-RADS scores (P < 0.05). The prediction model comprising 68Ga-PSMA PET/CT maximal standardized uptake value, PV and FPSA/TPSA had the highest AUC of 0.927 compared with that of other predictors alone (AUCs of 0.585 for PSA, 0.652 for mpMRI and 0.850 for 68Ga-PSMA PET/CT). The diagnostic sensitivity and specificity of the prediction model were 86.21% and 86.54%, respectively. CONCLUSION: Given the low diagnostic accuracy of regular PSA tests, a new prediction model based on the 68Ga-PSMA PET/CT SUVmax, PV and FPSA/TPSA was developed and validated, and this model could provide a more satisfactory predictive accuracy for CSPCa. This study provides a noninvasive prediction model with high accuracy for the diagnosis of CSPCa in the PSA gray zone, thus may be better avoiding unnecessary biopsy procedures.

Differences in whole-brain metabolism are associated with the expression of genes related to neurovascular unit integrity and synaptic plasticity in temporal lobe epilepsy.

PURPOSE: Temporal lobe epilepsy (TLE) is a common, polygenic epilepsy syndrome that involves glucose hypometabolism in the epileptogenic zone. However, the transcriptional and cellular signatures underlying the metabolism in TLE remain unclear. METHODS: In this retrospective study, 2-[18F]-fluoro-2-deoxy-D-glucose ([18F]FDG) positron emission tomography (PET) scans of TLE patients (n = 104) who underwent anterior temporal lobectomy were consecutively collected between 2016 and 2021. The transcriptional profiles of TLE risk genes across the brain were identified by the gene expression analyses from six TLE patients and twelve postmortem donors (six from the Allen Human Brain Atlas). Integrating the neuroimaging and transcriptomic data, we examined the relationship between the expression of TLE-associated genes and metabolic alterations in TLE. Furthermore, we performed functional enrichment analyses of the genes with higher weight in partial least squares regression using Metascape. RESULTS: A total of 104 patients with TLE (mean age 29 ± 9 years, 50% male) and 30 healthy controls (HCs) (mean age 31 ± 6 years, 53% male) were enrolled. Compared to that of HCs, patients with TLE showed hypometabolism in the temporal lobes and adjacent structures but hypermetabolism in the thalamus and basal ganglia. The cortical map of inter-group differences in cerebral metabolism was spatially correlated with the expression of a weighted combination of genes enriched in ontology terms and pathways related to neurovascular unit (NVU) integrity and synaptic plasticity. DISCUSSION: Our findings, combined with the analysis of neuroimaging and transcriptional data, suggest that genes related to NVU integrity and synaptic plasticity may drive alterations to brain metabolism that mediate the genetic risk of TLE.

Benign Prostatic Hyperplasia-Related False-Positive of Prostate-Specific Membrane Antigen-Positron Emission Tomography in the Diagnosis of Prostate Cancer: The Achilles' Heel of Biopsy-Free Radical Prostatectomy?

PURPOSE: Radical prostatectomy is one of the primary treatments for localized clinically significant prostate cancer. Generally, its application is based on prior biopsy. PSMA (prostate-specific membrane antigen)-PET (positron emission tomography) is considered promising in biopsy-free radical prostatectomy. The expression of PSMA in benign prostatic hyperplasia tissue and corresponding positive reaction are crucial concerns for a no-biopsy strategy. Currently, no study has explored the benign prostatic hyperplasia-related false-positive of PSMA-PET in the detection of prostate cancer. Furthermore, the influence of maximum standardized uptake value and Prostate Imaging Reporting & Data System on biopsy-free radical prostatectomy is also poorly characterized. MATERIALS AND METHODS: A retrospective study was conducted on patients who received PSMA-PET because of clinical suspicion of prostate cancer and were confirmed to have benign prostatic hyperplasia or prostate cancer. The receiver operating characteristic curve was generated for maximum standardized uptake value. Results of interest were the false-positive rate of PSMA-PET and the efficacy of maximum standardized uptake value or multiparametric MRI in excluding false-positives. RESULTS: The benign prostatic hyperplasia-related false-positive rate of PSMA-PET in detecting prostate cancer was 30%. Maximum standardized uptake value could effectively exclude benign prostatic hyperplasia and Grade Group 1 patients with an area under the curve of 0.86; the optimal maximum standardized uptake value cutoff value with 100% specificity was 15, with a sensitivity of 41%. Notably, the sensitivity and specificity of stringent PET score and Prostate Imaging Reporting & Data System criteria (both ≥4) in diagnosing clinically significant prostate cancer were 49% and 100%, respectively. CONCLUSIONS: Our findings revealed benign prostatic hyperplasia-related false-positive rate of PSMA-PET and provided a preliminary reference in biopsy-free radical prostatectomy.

Prediction of clinically significant prostate cancer using a novel 68Ga-PSMA PET-CT and multiparametric MRI-based model.

Background: There are some limitations in the commonly used methods for the detection of prostate cancer. There is a lack of nomograms based on multiparametric magnetic resonance imaging (mpMRI) and 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography-computed tomography (PET-CT) for the prediction of prostate cancer. The study seeks to compare the performance of mpMRI and 68Ga-PSMA PET-CT, and design a novel predictive model capable of predicting clinically significant prostate cancer (csPCa) before biopsy based on a combination of 68Ga-PSMA PET-CT, mpMRI, and patient clinical parameters. Methods: From September 2020 to June 2021, we prospectively enrolled 112 consecutive patients with no prior history of prostate cancer who underwent both 68Ga-PSMA PET-CT and mpMRI prior to biopsy at our clinical center. Univariate and multivariate regression analyses were used to identify predictors of csPCa, with a predictive model and its nomogram incorporating 68Ga-PSMA PET-CT, mpMRI, and the clinical predictors then being generated. The constructed model was evaluated using receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis, and further validated with the internal and external cohorts. Results: The model incorporated prostate-specific antigen density (PSAd), Prostate Imaging Reporting and Data System (PI-RADS) category, and maximum standardized uptake value (SUVmax), and it exhibited excellent predictive efficacy when applying to evaluate both training and validation cohorts [area under the curve (AUC): 0.936 and 0.940, respectively]. Compared with SUVmax alone, the model demonstrated excellent diagnostic performance with improved specificity (0.910, 95% CI: 0.824-0.963) and positive predictive values (0.811, 95% CI: 0.648-0.920). Calibration curve and decision curve analysis further confirmed that the model exhibited a high degree of clinical net benefit and low error rate. Conclusions: The constructed model in this study was capable of accurately predicting csPCa prior to biopsy with excellent discriminative ability. As such, this model has the potential to be an effective non-invasive approach for the diagnosis of csPCa.

The reconfiguration pattern of individual brain metabolic connectome for Parkinson's disease identification.

18F-Fluorodeoxyglucose positron emission tomography (18F-FDG PET) is widely employed to reveal metabolic abnormalities linked to Parkinson's disease (PD) at a systemic level. However, the individual metabolic connectome details with PD based on 18F-FDG PET remain largely unknown. To alleviate this issue, we derived a novel brain network estimation method for individual metabolic connectome, that is, Jensen-Shannon Divergence Similarity Estimation (JSSE). Further, intergroup difference between the individual's metabolic brain network and its global/local graph metrics was analyzed to investigate the metabolic connectome's alterations. To further improve the PD diagnosis performance, multiple kernel support vector machine (MKSVM) is conducted for identifying PD from normal control (NC), which combines both topological metrics and connection. Resultantly, PD individuals showed higher nodal topological properties (including assortativity, modularity score, and characteristic path length) than NC individuals, whereas global efficiency and synchronization were lower. Moreover, 45 most significant connections were affected. Further, consensus connections in occipital, parietal, and frontal regions were decrease in PD while increase in subcortical, temporal, and prefrontal regions. The abnormal metabolic network measurements depicted an ideal classification in identifying PD of NC with an accuracy up to 91.84%. The JSSE method identified the individual-level metabolic connectome of 18F-FDG PET, providing more dimensional and systematic mechanism insights for PD.

Metabolic profiles and correlation with surgical outcomes in mesial versus neocortical temporal lobe epilepsy.

AIMS: Differentiating mesial temporal lobe epilepsy (MTLE) and neocortical temporal lobe epilepsy (NTLE) remains challenging. Our study characterized the metabolic profiles between MTLE and NTLE and their correlation with surgical prognosis using 18 F-FDG-PET. METHODS: A total of 137 patients with intractable temporal lobe epilepsy (TLE) and 40 age-matched healthy controls were recruited. Patients were divided into the MTLE group (N = 91) and the NTLE group (N = 46). 18 F-FDG-PET was used to measure the metabolism of regional cerebra, which was analyzed using statistical parametric mapping. The volume of abnormal metabolism in cerebral regions and their relationship with surgical prognosis were calculated for each surgical patient. RESULTS: The cerebral hypometabolism of MTLE was limited to the ipsilateral temporal and insular lobes (p < 0.001, uncorrected). The NTLE patients showed hypometabolism in the ipsilateral temporal, frontal, and parietal lobes (p < 0.001, uncorrected). The MTLE patients showed extensive hypermetabolism in cerebral regions (p < 0.001, uncorrected). Hypermetabolism in NTLE was limited to the contralateral temporal lobe and cerebellum, ipsilateral frontal lobe, occipital lobe, and bilateral thalamus (p < 0.001, uncorrected). Among patients who underwent resection of epileptic lesions, 51 (67.1%) patients in the MTLE group and 10 (43.5%) in the NTLE group achieved Engel class IA outcome (p = 0.041). The volumes of metabolic increase for the frontal lobe or thalamus in the MTLE group were larger in non-Engel class IA patients than Engel class IA patients (p < 0.05). CONCLUSIONS: The spatial metabolic profile discriminated NTLE from MTLE. Hypermetabolism of the thalamus and frontal lobe in MTLE may facilitate preoperative counseling and surgical planning.

Synaptic Loss in Spinocerebellar Ataxia Type 3 Revealed by SV2A Positron Emission Tomography.

BACKGROUND: Severe reduced synaptic density was observed in spinocerebellar ataxia (SCA) in postmortem neuropathology, but in vivo assessment of synaptic loss remains challenging. OBJECTIVE SPINOCEREBELLAR ATAXIA TYPE 3: The objective of this study was to assess in vivo synaptic loss and its clinical correlates in spinocerebellar ataxia type 3 (SCA3) patients by synaptic vesicle glycoprotein 2A (SV2A)-positron emission tomography (PET) imaging. METHODS: We recruited 74 SCA3 individuals including preataxic and ataxic stages and divided into two cohorts. All participants received SV2A-PET imaging using 18 F-SynVesT-1 for synaptic density assessment. Specifically, cohort 1 received standard PET procedure and quantified neurofilament light chain (NfL), and cohort 2 received simplified PET procedure for exploratory purpose. Bivariate correlation was performed between synaptic loss and clinical as well as genetic assessments. RESULTS: In cohort 1, significant reductions of synaptic density were observed in cerebellum and brainstem in SCA3 ataxia stage compared to preataxic stage and controls. Vermis was found significantly involved in preataxic stage compared to controls. Receiver operating characteristic (ROC) curves highlighted SV2A of vermis, pons, and medulla differentiating preataxic stage from ataxic stage, and SV2A combined with NfL improved the performance. Synaptic density was significantly negatively correlated with disease severity in cerebellum and brainstem (International Co-operative Ataxia Rating Scale: ρ ranging from -0.467 to -0.667, P ≤ 0.002; Scale of Assessment and Rating of Ataxia: ρ ranging from -0.465 to -0.586, P ≤ 0.002). SV2A reduction tendency of cerebellum and brainstem identified in cohort 1 was observed in cohort 2 with simplified PET procedure. CONCLUSIONS: We first identified in vivo synaptic loss was related to disease severity of SCA3, suggesting SV2A PET could be a promising clinical biomarker for disease progression of SCA3. © 2023 International Parkinson and Movement Disorder Society.

Analysis of carotid vulnerable plaque MRI high-risk features and clinical risk factors associated with concomitant acute cerebral infarction.

BACKGROUND: This study aimed to investigate the correlation between the high-risk characteristics of high-resolution MRI carotid vulnerable plaques and the clinical risk factors and concomitant acute cerebral infarction (ACI). METHODS: Forty-five patients diagnosed with a single vulnerable carotid plaque by MRI were divided into two groups based on whether they had ipsilateral ACI. The clinical risk factors and the observation values or frequency of occurrence of high-risk MRI phenotypes of plaque volume, LRNC, IPH and ulcer were statistically compared between the two groups. RESULTS: A total of 45 vulnerable carotid artery plaques were found in 45 patients, 23 patients with ACI and 22 patients without ACI. There were no significant differences in age, sex, smoking, serum TC, TG and LDL between the two groups (all P > 0.05), but the ACI group had significantly more patients with hypertension (P < 0.05) and the without ACI group coronary heart disease (P < 0.05). The volume of vulnerable carotid plaque in the group with ACI (1004.19 ± 663.57 mm3) was significantly larger than that in the group without ACI (487.21 ± 238.64 mm3) (P < 0.05). The phenotype of vulnerable carotid artery plaque was 13 cases of LRNC, 8 cases of LRNC + IPH, 5 cases of LRNC + Ulcer, and 19 cases of LRNC + IPH + Ulcer. There was no significant difference in this distribution between the two groups (all P > 0.05) with the exception of LRNC + IPH + Ulcer. The 14 cases of LRNC + IPH + LRNC + IPH + Ulcer (60.87%) in the group with ACI and was significantly greater than the 5 (22.73%) in patients without ACI (P < 0.05). CONCLUSION: It is preliminarily thought that hypertension is the main clinical risk factor for vulnerable carotid plaques with ACI and the combination of plaque volume with vulnerable carotid plaque and LRNC + IPH + Ulcer is a high-risk factor for complicated ACI. It has high clinical therapeutic value due to the accurate diagnosis of responsible vessels and plaques with high-resolution MRI.

Brain metabolic signatures in patients with genetic and nongenetic amyotrophic lateral sclerosis.

AIMS: To study the brain metabolic signature in Chinese amyotrophic lateral sclerosis (ALS) patients and compare the difference in brain metabolic patterns between ALS with and without genetic variants. METHODS: We included 146 patients with ALS and 128 healthy controls (HCs). All patients with ALS underwent genetic testing to screen for ALS related genetic variants and were then divided into genetic (n = 22) and nongenetic ALS (n = 93) subgroups. All participants underwent brain 18 F-FDG-PET scans. Group comparisons were performed using the two-sample t-test model of SPM12. RESULTS: We identified a large of hypometabolic clusters in ALS patients as compared with HCs, especially in the bilateral basal ganglia, midbrain, and cerebellum. Moreover, hypometabolism in the bilateral temporal lobe, precentral gyrus and hypermetabolism in the left anterior cingulate, occipital lobe, and bilateral frontal lobe were also found in ALS patients as compared with HCs. Compared with nongenetic ALS patients, genetic ALS patients showed hypometabolism in the right postcentral gyrus, precuneus, and middle occipital gyrus. The incidence of sensory disturbance in patients with genetic ALS was higher than that in patients with nongenetic ALS (5 of 22 [22.72%] vs. 7 of 93 [7.52%], p = 0.036). CONCLUSIONS: Our investigation provided unprecedented evidence of relative hypometabolism in the midbrain and cerebellum in ALS patients. Genetic ALS patients showed a specific signature of brain metabolism and a higher incidence of sensory disturbance, indicating that genetic factors may be an underlying cause affecting the brain metabolism and increasing the risk of sensory disturbance in ALS.