Injured sensory neurons-derived galectin-3 contributes to neuropathic pain via programming microglia in the spinal dorsal horn.

Emerging studies have demonstrated spinal microglia play a critical role in central sensitization and contribute to chronic pain. Although several mediators that contribute to microglia activation have been identified, the mechanism of microglia activation and its functionally diversified mechanisms in pathological pain are still unclear. Here we report that injured sensory neurons-derived Galectin-3 (Gal3) activates and reprograms microglia in the spinal dorsal horn (SDH) and contributes to neuropathic pain. Firstly, Gal3 is predominantly expressed in the isolectin B4 (IB4)-positive non-peptidergic sensory neurons and significantly up-regulated in dorsal root ganglion (DRG) neurons and primary afferent terminals in SDH in the partial sciatic nerve ligation (pSNL)-induced neuropathic pain model. Gal3 knockout (Gal3 KO) mice showed a significant decrease in mechanical allodynia and Gal3 inhibitor TD-139 produced a significant anti-allodynia effect in the pSNL model. Furthermore, pSNL-induced microgliosis was compromised in Gal3 KO mice. Additionally, intrathecal injection of Gal3 produces remarkable mechanical allodynia by direct activation of microglia, which have enhanced inflammatory responses with TNF-α and IL-1ß up-regulation. Thirdly, using single-nuclear RNA sequencing (snRNA-seq), we identified that Gal3 targets microglia and induces reprogramming of microglia, which may contribute to neuropathic pain establishment. Finally, Gal3 enhances excitatory synaptic transmission in excitatory neurons in the SDH via microglia activation. Our findings reveal that injured sensory neurons-derived Gal3 programs microglia in the SDH and contribute to neuropathic pain.

Use of 18F-FDG PET/MRI as an Initial Staging Procedure for Nasopharyngeal Carcinoma.

BACKGROUND: Compared with the conventional work-up (CWU) including computed tomography (CT) of the chest and abdomen, MRI of the head and neck, and skeletal scintigraphy, positron emission tomography (PET)/MRI might improve diagnostic accuracy, shorten the work-up time, and reduce false-positive (FP) findings in patients with nasopharyngeal carcinoma (NPC). However, evidence of cost-effectiveness is needed for the adoption of PET/MRI for the initial staging in NPC. PURPOSE: To evaluate the cost-effectiveness and clinical value of PET/MRI as an initial staging procedure for NPC. STUDY TYPE: Retrospective cohort cost effectiveness study. SUBJECTS: Three hundred forty-three patients with a median age of 51 (13-81) years underwent PET/MRI before treatment (the PET/MRI group) and the remaining 677 patients with a median age of 55 (15-95) years only underwent CWU (the CWU group). There were 80 (23.3%) females and 193 (28.5%) females in the PET/MRI and CWU groups, respectively. FIELD STRENGTH/SEQUENCE: 3-T integrated PET/MRI system, diffusion-weighted echo-planar imaging (b = 0 and 1000 s/mm2 ) and [18F] fluorodeoxyglucose PET. ASSESSMENT: The primary end point was the FP rate. Costs were determined as issued in 2021 by the Medical Insurance Administration Bureau of Zhejiang, China. STATISTICAL TESTS: Incremental cost effectiveness ratio (ICER) measured cost of using PET/MRI per percent of patients who avoided a FP. A P-value <0.05 was considered statistically significant. RESULTS: For the whole group, the de novo metastatic disease rate was 5.2% (53/1020). A total of 187 patients with FP results were observed. Significantly more patients with FP results were observed in the CWU group compared to the PET/MRI group (25.6% vs. 4.1%). The ICER was $54 for each percent of patients avoiding a FP finding. DATA CONCLUSION: Compared with CWU, PET/MRI may reduce the FP risk. Furthermore, PET/MRI may be cost-effective as an initial staging procedure for NPC. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 6.

Spatiotemporal Excitation Module-based CNN for Diagnosis of Hepatic Malignancy in Four-phase CT Images.

Liver cancer is a part of the common causes of cancer death worldwide, and the accurate diagnosis of hepatic malignancy is important for effective next treatment. In this paper, we propose a convolutional neural network (CNN) based on a spatiotemporal excitation (STE) module for identification of hepatic malignancy in four-phase computed tomography (CT) images. To enhance the display detail of lesion, we expand single-channel CT images into three channels by using the channel expansion method. Our proposed STE module consists of a spatial excitation (SE) module and a temporal interaction (TI) module. The SE module calculates the temporal differences of CT slices at the feature level, which is used to excite shape-sensitive channels of the lesion features. The TI module shifts a portion of the channels in the temporal dimension to exchange information among the current CT slice and adjacent CT slices. Four-phase CT images of 398 patients diagnosed with hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are used for experiments and five cross-validations are performed. Our model achieved average accuracy of 85.00% and average AUC of 88.91% for classifying HCC and ICC.Clinical Relevance- The proposed deep learning-based model can perform HCC and ICC recognition tasks based on four-phase CT images, assisting doctors to obtain better diagnostic performance.

The impact of the COVID-19 pandemic on nasopharyngeal carcinoma extent at FDG PET/MR staging: The NPCOVIPET study.

BACKGROUND: To evaluate the impact of coronavirus disease 2019 (COVID-19) pandemic on disease extent in patients with nasopharyngeal carcinoma (NPC) using 18 fuorodeoxyglucose (FDG) positron emission tomography (PET)/magnetic resonance imaging (MRI). METHODS: This retrospective cohort study included biopsy-proven, newly diagnosed NPC patients using whole-body FDG PET/MR staging in two selected intervals: 1 May 2017 to 31 January 2020 (Group A, the pre-COVID-19 period), and 1 February 2020 to 30 June 2021 (Group B, the COVID-19 period). RESULTS: Three-hundred and ninety patients were included. No significant difference was observed in terms of T classification, N classification, overall stage, N stations, and M stations between the two groups (p > 0.05). For the involved neck node levels, more patients had developed level Vc metastasis in the group B (p = 0.044). CONCLUSION: Although the overall stage was not affected, more patients with NPC had developed level Vc metastasis in the era of COVID-19.

Assessment of bone lesions with 18 F-FDG PET/MRI in patients with nasopharyngeal carcinoma.

PURPOSE: The purpose of this study is to evaluate the role of 18 fluorodeoxyglucose ( 18 F) PET/MRI ( 18 F-FDG PET/MRI) for detecting bone metastasis in nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: Between May 2017 and May 2021, 58 histologically proven NPC patients who underwent both 18 F-FDG PET/MRI and 99m Tc-MDP planar bone scintigraphy (PBS) for tumor staging were included. With the exception of the head, the skeletal system was classified into four groups: the spine, the pelvis, the thorax and the appendix. RESULTS: Nine (15.5 %) of 58 patients were confirmed to have bone metastasis. There was no statistical difference between PET/MRI and PBS in patient-based analysis ( P = 0.125). One patient with a super scan was confirmed to have extensive and diffuse bone metastases and excluded for lesion-based analysis. Of the 57 patients, all 48 true metastatic lesions were positive in PET/MRI whereas only 24 true metastatic lesions were positive in PBS (spine: 8, thorax: 0, pelvis: 11 and appendix: 5). PET/MRI was observed to be more sensitive than PBS in lesion-based analysis (sensitivity 100.0% versus 50.0 %; P < 0.001). CONCLUSIONS: Compared with PBS for tumor staging of NPC, PET/MRI was observed to be more sensitive in the lesion-based analysis of bone metastasis.

AIGAN: Attention-encoding Integrated Generative Adversarial Network for the reconstruction of low-dose CT and low-dose PET images.

X-ray computed tomography (CT) and positron emission tomography (PET) are two of the most commonly used medical imaging technologies for the evaluation of many diseases. Full-dose imaging for CT and PET ensures the image quality but usually raises concerns about the potential health risks of radiation exposure. The contradiction between reducing the radiation exposure and remaining diagnostic performance can be addressed effectively by reconstructing the low-dose CT (L-CT) and low-dose PET (L-PET) images to the same high-quality ones as full-dose (F-CT and F-PET). In this paper, we propose an Attention-encoding Integrated Generative Adversarial Network (AIGAN) to achieve efficient and universal full-dose reconstruction for L-CT and L-PET images. AIGAN consists of three modules: the cascade generator, the dual-scale discriminator and the multi-scale spatial fusion module (MSFM). A sequence of consecutive L-CT (L-PET) slices is first fed into the cascade generator that integrates with a generation-encoding-generation pipeline. The generator plays the zero-sum game with the dual-scale discriminator for two stages: the coarse and fine stages. In both stages, the generator generates the estimated F-CT (F-PET) images as like the original F-CT (F-PET) images as possible. After the fine stage, the estimated fine full-dose images are then fed into the MSFM, which fully explores the inter- and intra-slice structural information, to output the final generated full-dose images. Experimental results show that the proposed AIGAN achieves the state-of-the-art performances on commonly used metrics and satisfies the reconstruction needs for clinical standards.

Microglial Cannabinoid CB2 Receptors in Pain Modulation.

Pain, especially chronic pain, can strongly affect patients' quality of life. Cannabinoids ponhave been reported to produce potent analgesic effects in different preclinical pain models, where they primarily function as agonists of Gi/o protein-coupled cannabinoid CB1 and CB2 receptors. The CB1 receptors are abundantly expressed in both the peripheral and central nervous systems. The central activation of CB1 receptors is strongly associated with psychotropic adverse effects, thus largely limiting its therapeutic potential. However, the CB2 receptors are promising targets for pain treatment without psychotropic adverse effects, as they are primarily expressed in immune cells. Additionally, as the resident immune cells in the central nervous system, microglia are increasingly recognized as critical players in chronic pain. Accumulating evidence has demonstrated that the expression of CB2 receptors is significantly increased in activated microglia in the spinal cord, which exerts protective consequences within the surrounding neural circuitry by regulating the activity and function of microglia. In this review, we focused on recent advances in understanding the role of microglial CB2 receptors in spinal nociceptive circuitry, highlighting the mechanism of CB2 receptors in modulating microglia function and its implications for CB2 receptor- selective agonist-mediated analgesia.

Detection and staging of recurrent or metastatic nasopharyngeal carcinoma in the era of FDG PET/MR.

PURPOSE: The aim of this pilot study was to evaluate the accuracy of 18 fluorodeoxyglucose (FDG) PET/MR imaging in detection and staging of recurrent or metastatic NPC. PATIENTS AND METHODS: The PET/MR scans of 60 patients with clinically diagnosed recurrent or metastatic NPC between April 2017 and November 2019 were included in this study. Findings were evaluated according to the eighth edition of the American Joint Committee on Cancer staging system. Final diagnosis was confirmed at biopsy or imaging follow-up for at least 6 months. RESULTS: Of the 60 patients, 25, 26 and 42 had developed local lesions, regional nodal metastases and distant metastases, respectively. The overall accuracy of PET/MR imaging for staging of recurrent or metastatic NPC was 88.3%. CONCLUSIONS: For recurrent or metastatic NPC, 18 FDG PET/MRI might serve as a single-step staging modality.

High-resolution pediatric age-specific 18F-FDG PET template: a pilot study in epileptogenic focus localization.

BACKGROUND: PET imaging has been widely used in diagnosis of neurological disorders; however, its application to pediatric population is limited due to lacking pediatric age-specific PET template. This study aims to develop a pediatric age-specific PET template (PAPT) and conduct a pilot study of epileptogenic focus localization in pediatric epilepsy. METHODS: We recruited 130 pediatric patients with epilepsy and 102 age-matched controls who underwent 18F-FDG PET examination. High-resolution PAPT was developed by an iterative nonlinear registration-averaging optimization approach for two age ranges: 6-10 years (n = 17) and 11-18 years (n = 50), respectively. Spatial normalization to the PAPT was evaluated by registration similarities of 35 validation controls, followed by estimation of potential registration biases. In a pilot study, epileptogenic focus was localized by PAPT-based voxel-wise statistical analysis, compared with multi-disciplinary team (MDT) diagnosis, and validated by follow-up of patients who underwent epilepsy surgery. Furthermore, epileptogenic focus localization results were compared among three templates (PAPT, conventional adult template, and a previously reported pediatric linear template). RESULTS: Spatial normalization to the PAPT significantly improved registration similarities (P < 0.001), and nearly eliminated regions of potential biases (< 2% of whole brain volume). The PAPT-based epileptogenic focus localization achieved a substantial agreement with MDT diagnosis (Kappa = 0.757), significantly outperforming localization based on the adult template (Kappa = 0.496) and linear template (Kappa = 0.569) (P < 0.05). The PAPT-based localization achieved the highest detection rate (89.2%) and accuracy (80.0%). In postsurgical seizure-free patients (n = 40), the PAPT-based localization also achieved a substantial agreement with resection areas (Kappa = 0.743), and the highest detection rate (95%) and accuracy (80.0%). CONCLUSION: The PAPT can significantly improve spatial normalization and epileptogenic focus localization in pediatric epilepsy. Future pediatric neuroimaging studies can also benefit from the unbiased spatial normalization by PAPT. TRIAL REGISTRATION: NCT04725162: https://clinicaltrials.gov/ct2/show/NCT04725162.

Locoregional Extension Patterns of Nasopharyngeal Carcinoma Detected by FDG PET/MR.

PURPOSE: We sought to define the locoregional extension patterns of nasopharyngeal carcinomas (NPCs) by positron emission tomography (PET)/magnetic resonance imaging (MRI) and to improve clinical target volume (CTV) delineation. METHODS: Between May 2017 and March 2021, 331 consecutive patients with nonmetastatic NPCs who underwent pretreatment, simultaneous whole-body PET/MRI for staging were included in this study. RESULTS: The high-risk regions included the base of the sphenoid bone, the prestyloid compartment, prevertebral muscle, foramen lacerum, medial pterygoid plate, sphenoidal sinus, clivus, petrous apex, and foramen ovale. When the high-risk regions were invaded, the incidence rates of tumor invasion into the medium-risk regions increased. In contrast, when the high-risk regions were not involved, the incidence rates of tumor invasion into the medium-risk regions were mostly less than 10%, excluding the post-styloid compartment and oropharynx. According to the updated consensus guidelines of the neck node levels for head and neck tumors from 2013, level IIa (77.3%, 256/331), level IIb (75.8%, 251/331), and level VIIa (71.3%, 236/331) were the most frequently involved levels, followed by levels III (42.6%), Va (13.9%), IVa (8.8%), IVb (3.6%), Ib (3.6%), Vb (2.4%), VIIb (2.4%), VIII (1.8%), Vc (0.9%), and Xa (0.3%). Skip lymph node metastasis occurred in only 1.9% of patients. CONCLUSIONS: For NPCs, primary disease and regional lymph node spread follow an orderly pattern, and a skip pattern of lymph node metastasis was unusual. Involved level radiotherapy might be feasible for cervical lymph node levels below the caudal border of cricoid cartilage and level VIIb.

Estimation of Nuclear Medicine Exposure Measures Based on Intelligent Computer Processing.

This paper provides an in-depth discussion and analysis of the estimation of nuclear medicine exposure measurements using computerized intelligent processing. The focus is on the study of energy extraction algorithms to obtain a high energy resolution with the lowest possible ADC sampling rate and thus reduce the amount of data. This paper focuses on the direct pulse peak extraction algorithm, polynomial curve fitting algorithm, double exponential function curve fitting algorithm, and pulse area calculation algorithm. The detector output waveforms are obtained with an oscilloscope, and the analysis module is designed in MATLAB. Based on these algorithms, the data obtained from six different lower sampling rates are analyzed and compared with the results of the high sampling rate direct pulse peak extraction algorithm and the pulse area calculation algorithm, respectively. The correctness of the compartment model was checked, and the results were found to be realistic and reliable, which can be used for the analysis of internal exposure data in radiation occupational health management, estimation of internal exposure dose for nuclear emergency groups, and estimation of accidental internal exposure dose. The results of the compartment model of the respiratory tract and the compartment model of the digestive tract can be used to calculate the distribution and retention patterns of radionuclides and their compounds in the body, which can be used to assess the damage of radionuclide internal contamination and guide the implementation of medical treatment.

Feasibility of multiparametric imaging with PET/MR in nasopharyngeal carcinoma: A pilot study.

OBJECTIVE: The aim of this pilot study was to explore the integrated positron emission tomography and magnetic resonance imaging scanner (PET/MR) for biological characterization of nasopharyngeal carcinoma (NPC) and potential therapeutic applications of dose painting (DP). PATIENTS AND METHODS: Twenty-one NPC patients with PET/MR were included in this study. Overlap of tumor volumes was analyzed on T2-weighted images (volume of interest, VOIT2), diffusion-weighted magnetic resonance imaging (VOIDWI) and 18F-fluorodeoxyglucose positron emission tomography (VOIPET). The overlap percentages of low-metabolic sub-region (cluster 1) and high-metabolic sub-region (cluster 2) in VOIPET and VOIDWI were analyzed by cluster analysis. RESULTS: Both the VOIDWI and VOIPET were encompassed in the VOIT2, respectively 99.6% and 97.5%. The median tumor overlap was 94.4% (VOIDWI within VOIPET). The median overlap of cluster 2 in VOIPET and VOIDWI was 43.61% (27.67-52.66%) and 21.86%(10.47-40.89%), respectively. The median overlap of cluster 1 in VOIPET and VOIDWI was 48.03% (23.91-63.15%) and 24.40% (7.44-51.44%), respectively. Separation between clusters appeared to be defined by a SUV value. CONCLUSION: For NPC, the VOIs of DWI and FDG PET were not overlapped completely and the volume defined by cluster-analysis might be meaningful for DP.

18F-FDG PET/CT for the early prediction of the response rate and survival of patients with recurrent or metastatic breast cancer.

The present study aimed to explore the value of fludeoxyglucose F 18 positron emission tomography-computed tomography (PET/CT) for the early prediction of chemotherapy remission rates and survival in patients with recurrent and metastatic breast cancer. A total of 24 patients diagnosed with recurrent or metastatic breast cancer between 2009 and 2014 were enrolled. All patients underwent a PET/CT examination prior to (PET/CT1) and following (PET/CT2) chemotherapy. Differences of PET/CT1 maximal standardized uptake values (SUVmax), PET/CT2 SUVmax, ΔSUVmax and the ΔSUVmax% between objective remission (OR) and non-OR groups were measured. Survival differences between OR and non-OR groups and the overall survival (OS) between metabolic responsive and metabolic non-responsive groups were analyzed. In the present study, it was revealed that ΔSUVmax and ΔSUVmax% were significantly higher in the OR group compared with the non-OR group (P<0.001). Overall survival was significantly prolonged in the OR and metabolic responder groups compared with their respective control groups (P<0.001 and P<0.01, respectively). ΔSUVmax% were significantly positively associated with OS (r2=0.266; P<0.01). In conclusion, PET/CT may be valuable for the early prediction of the chemotherapy efficacy and survival of patients with recurrent or metastatic breast cancer.