Diagnostic Value of Dual-Energy CT Virtual Noncalcium for the Assessment of Bone Marrow Edema of Wrist in Patients with Rheumatoid Arthritis.

RATIONALE AND OBJECTIVES: To evaluate the value of dual-energy CT (DECT) virtual noncalcium (VNCa) images in the diagnosis of wrist bone marrow edema (BME) in patients with rheumatoid arthritis (RA). MATERIALS AND METHODS: 43 patients with wrist involvement in active RA prospectively underwent DECT and MRI. Functional DECT images reconstruction yielded VNCa images. MRI served as the reference standard for diagnosing BME. BME diagnosis differences between VNCa images and MRI were compared. Differences in CT values between BME and normal bone marrow were assessed. The optimal CT value for detecting BME in VNCa images was determined through ROC curve analysis. The correlation between VNCa images scores and RA disease activity was evaluated. RESULTS: There was a high agreement between VNCa images and MRI in diagnosing BME (Kappa=0.831). VNCa images showed a significant difference in CT values between BME and normal bone marrow (P < 0.001). A cut-off value of - 54.8 HU yielded a sensitivity, specificity, and accuracy of 90.72%, 94.30%, and 93.33%, respectively, for detecting BME on VNCa images. The area under the ROC curve was 0.937 for distinguishing BME from normal bone marrow. Conventional CT images showed no statistically significant difference (P = 0.174) in CT values between BME and normal bone marrow. The VNCa images BME scores were positively correlated with RA disease activity (r = 0.399). CONCLUSION: The DECT VNCa technique demonstrates its potential for diagnosing wrist BME in patients with RA and provides a valuable tool for assessing disease activity in RA. IMPORTANT FINDINGS: The DECT VNCa technique has the ability to distinguish between BME and normal bone marrow. The VNCa images BME scores were positively correlated with the disease activity in RA.

Platelets as delivery vehicles for targeted enrichment of NO· to cerebral glioma for magnetic resonance imaging.

Using a magnetic resonance imaging (MRI) contrast agent, MRI has made substantial contributions to glioma diagnosis. Metal-free MRI agents, such as the nano free radical nitric oxide (NO·) micelle, can overcome the inherent toxicity of metal-based agents in certain patient populations. However, the low spatial resolution of nano NO· micelle in MRI limits its clinical development. In this study, we pretreated platelets (PLTs) and loaded them with nano NO· micelles to synthesize NO·@PLT, which can overcome the low contrast and poor in vivo stability of nitroxide-based MRI contrast agents. The PLTs can serve as potential drug carriers for targeting and delivering nano NO· micelles to gliomas and thus increase the contrast in T1-weighted imaging (T1WI) of MRI. This drug carrier system uses the unique tumor-targeting ability of PLTs and takes advantage of the high signal presentation of steady nano NO· micelles in T1WI, thereby ultimately achieving signal amplification of glioma in T1WI. With the effect of PLTs-tumor cell adhesion, NO·@PLT has per-nitroxide transverse relativities of approximately 2-fold greater than those of free NO· particles. These features allow a sufficient NO·@PLT concentration to accumulate in murine subcutaneous glioma tumors up from 5 min to 2.5 h (optimum at 1.5 h) after systemic administration. This results in MRI contrast comparable to that of metal-based agents. This study established a promising metal-free MRI contrast agent, NO·@PLT, for glioma diagnosis, because it has superior spatial resolution owing to its high glioma-targeting ability and has significant translational implications in the clinic.

Radiomics Based on Contrast-Enhanced CT for Recognizing c-Met-Positive Hepatocellular Carcinoma: a Noninvasive Approach to Predict the Outcome of Sorafenib Resistance.

OBJECTIVES: The purpose of our project was to investigate the effectiveness of radiomic features based on contrast-enhanced computed tomography (CT) that can detect the expression of c-Met in hepatocellular carcinoma (HCC) and to validate its efficacy in predicting the outcome of sorafenib resistance. MATERIALS AND METHODS: In total, 130 patients (median age, 60 years) with pathologically confirmed HCC who underwent contrast material-enhanced CT from October 2012 to July 2020 were randomly divided into a training set (n = 91) and a test set (n = 39). Radiomic features were extracted from arterial phase (AP), portal venous phase (VP) and delayed phase (DP) images of every participant's enhanced CT images. RESULTS: The entire group comprised 39 Met-positive and 91 Met-negative patients. The combined model, which included the clinical factors and the radiomic features, performed well in the training (area under the curve [AUC] = 0.878) and validation (AUC = 0.851) cohorts. The nomogram, which relied on the combined model, fits well in the calibration curves. Decision curve analysis (DCA) further confirmed that the clinical valuation of the nomogram achieved comparable accuracy in c-Met prediction. Among another 20 patients with HCC who had received sorafenib, the predicted high-risk group had shorter overall survival (OS) than the predicted low-risk group (p < 0.05). CONCLUSION: A multivariate model acquired from three phases (AP, VP and DP) of enhanced CT, HBV-DNA and γ glutamyl transpeptidase isoenzyme II (GGT-II) could be considered a satisfactory preoperative marker of the expression of c-Met in patients with HCC. This approach may help in overcoming sorafenib resistance in advanced HCC.

Ferroptosis-Related Immune Genes in Hematological Diagnosis of Parkinson's Diseases.

Emerging evidence suggested that ferroptosis and immune activation, as well as their interactions, played a crucial role in the occurrence and progression of Parkinson's disease (PD). However, whether this interaction could serve as the basis for a hematological diagnosis of PD remained poorly understood. This study aimed to construct a novel hematological model for PD diagnosis based on the ferroptosis-related immune genes. The brain imaging of PD patients was obtained from the Affiliated Hospital of Nantong University. We used least absolute shrinkage and selection operator (LASSO) to identify the optimal signature ferroptosis-related immune genes based on six gene expression profile datasets of substantia nigra (SN) and peripheral blood of PD patients. Then we used the support vector machine (SVM) classifier to construct the hematological diagnostic model named Ferr.Sig for PD. Gene set enrichment analysis was utilized to execute gene functional annotation. The brain imaging and functional annotation analysis revealed prominent iron deposition and immune activation in the SN region of PD patients. We identified a total of 17 signature ferroptosis-related immune genes using LASSO method and imported them to SVM classifier. The Ferr.Sig model exhibited a high diagnostic accuracy, and its area under the curve (AUC) for distinguishing PD patients from healthy controls in the training and internal validation cohort reached 0.856 and 0.704, respectively. We also used the Ferr.Sig into other external validation cohorts, and a comparable AUC with the internal cohort was obtained, with the AUC of 0.727 in Scherzer's cohort, 0.745 in Roncagli's cohort, and 0.778 in Meiklejohn's cohort. Furthermore, the diagnostic performance of Ferr.Sig was not interfered by the other neurodegenerative diseases. This study revealed the value of ferroptosis-related immune genes in PD diagnosis, which may provide a novel direction and strategy for the development of novel biomarkers with less invasiveness, low cost, and high accuracy for PD screening and diagnosis.

DL-3-n-butylphthalide alleviates motor disturbance by suppressing ferroptosis in a rat model of Parkinson's disease.

DL-3-n-butylphthalide (NBP)-a compound isolated from Apium graveolens seeds-is protective against brain ischemia via various mechanisms in humans and has been approved for treatment of acute ischemic stroke. NBP has shown recent potential as a treatment for Parkinson's disease. However, the underlying mechanism of action of NBP remains poorly understood. In this study, we established a rat model of Parkinson's disease by intraperitoneal injection of rotenone for 28 successive days, followed by intragastric injection of NBP for 14-28 days. We found that NBP greatly alleviated rotenone-induced motor disturbance in the rat model of Parkinson's disease, inhibited loss of dopaminergic neurons and aggregation of α-synuclein, and reduced iron deposition in the substantia nigra and iron content in serum. These changes were achieved by alterations in the expression of the iron metabolism-related proteins transferrin receptor, ferritin light chain, and transferrin 1. NBP also inhibited oxidative stress in the substantia nigra and protected mitochondria in the rat model of Parkinson's disease. Our findings suggest that NBP alleviates motor disturbance by inhibition of iron deposition, oxidative stress, and ferroptosis in the substantia nigra.

A radiomics model based on DCE-MRI and DWI may improve the prediction of estimating IDH1 mutation and angiogenesis in gliomas.

PURPOSE: To investigate the value of a radiomics model based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion weighted imaging (DWI) in estimating isocitrate dehydrogenase 1 (IDH1) mutation and angiogenesis in gliomas. METHOD: One hundred glioma patients with DCE-MRI and DWI were enrolled in this study (training and validation groups with a ratio of 7:3). The IDH1 genotypes and expression of vascular endothelial growth factor (VEGF) in gliomas were assessed by immunohistochemistry. Radiomics features were extracted by an open source software (3DSlicer) and reduced using Least absolute shrinkage and selection operator (Lasso). The support vector machine (SVM) model was developed based on the most useful predictive radiomics features. The conventional model was built by the selected clinical and morphological features. Finally, a combined model including radiomics signature, age and enhancement degree was established. Receiver operator characteristic (ROC) curve was implemented to assess the diagnostic performance of the three models. RESULTS: For IDH1 mutation, the combined model achieved the highest area under curve (AUC) in comparison with the SVM and conventional models (training group, AUC = 0.967, 0.939 and 0.906; validation group, AUC = 0.909, 0.880 and 0.842). Furthermore, the SVM model showed good diagnostic performance in estimating gliomas VEGF expression (validation group, AUC = 0.919). CONCLUSIONS: The radiomics model based on DCE-MRI and DWI can have a considerable effect on the evaluation of IDH1 mutation and angiogenesis in gliomas.

Endoscopy during neurotomy of the nervus intermedius for nervus intermedius neuralgia: a case report.

Nervus intermedius neuralgia (NIN) is a rare craniofacial neuralgia with features of paroxysmal pain in the deep ear. Because of sensory nerves overlap in the ear, the diagnosis of NIN is often difficult and not definitive. Here, we present the case of a 70-year-old woman who had deep-ear pain for more than 4 years and was diagnosed with trigeminal neuralgia and treated with carbamazepine without relief in another hospital. Magnetic resonance tomographic angiography revealed no neurovascular conflict with the trigeminal nerve, whereas the anterior inferior cerebellar artery (AICA) was close to the VII/VIII complex. We performed left-sided suboccipital retrosigmoid craniotomy. Surgical exploration under endoscopy clearly showed that the nervus intermedius was compressed by the AICA from behind. The ear pain was completely relieved immediately after nervus intermedius sectioning. The intraoperative findings and postoperative results confirmed that the compression of the nervus intermedius by the AICA caused the otalgia. A patient's specific pain, combined with preoperative imaging examination, is useful in the diagnosis of NIN. Neuroendoscopy has the advantages of enabling a clear field of view and close observation, thus aiding in the identification and accurate cutting of the nervus intermedius during the operation.

Pathological Grade-Associated Transcriptome Profiling of lncRNAs and mRNAs in Gliomas.

The aim of the present study was to explore the expression profiles of lncRNAs and mRNAs in glioma patients and to elucidate any potential relationship between lncRNAs and mRNAs in glioma. High-throughput transcriptome sequencing of mRNAs and lncRNAs from six normal tissues and 16 glioma tissues (grade II, six cases; grade III, four cases; and grade IV, six cases) was performed. Series test of cluster (STC) analysis was used to screen significant trending models associated with glioma. Gene co-expression networks were constructed for the differentially expressed lncRNAs and mRNAs, and gene-ontology (GO) and pathway-enrichment analyses were further performed. Quantitative real-time PCR was performed to validate the five most differentially expressed lncRNAs and mRNAs. After filtering the raw sequencing data, we found 578 lncRNAs and 3,216 mRNAs that were significantly dysregulated in glioma (fold change ≥ 2, p < 0.05). Twenty model profiles of lncRNA and 10 model profiles of mRNA were summarized, and three patterns of lncRNAs and two patterns of mRNAs were of clinical significance. Three gene co-expression networks between mRNAs and lncRNAs were built to clarify the relationship between lncRNAs and mRNAs in glioma. GO and pathway analyses indicated that the differentially expressed lncRNAs and mRNAs were enriched in several biological processes and signaling pathways associated with tumorigenesis. Both lncRNAs and mRNAs exhibited dynamic differential expression profiles that indicated their potential roles in different degrees of glioma malignancy. A series of bioinformatics analyses indicated that most of these lncRNAs and mRNAs are involved in important biological processes and pathways associated with the pathogenesis of glioma. These results provide potential directions and valuable resources for future investigations via the comprehensive integration of these lncRNAs and mRNAs.

Combination Glioma Therapy Mediated by a Dual-Targeted Delivery System Constructed Using OMCN-PEG-Pep22/DOX.

Accumulating studies have investigated the efficacy of receptor-mediated delivery of hydrophobic drugs in glioma chemotherapy. Here, a delivery vehicle comprising polyethylene glycol (PEG) and oxidized nanocrystalline mesoporous carbon particles (OMCN) linked to the Pep22 polypeptide targeting the low-density lipoprotein receptor (LDLR) is designed to generate a novel drug-loaded system, designated as OMCN-PEG-Pep22/DOX (OPPD). This system effectively targets glioma cells and the blood-brain barrier and exerts therapeutic efficacy through both near-infrared (NIR) photothermal and chemotherapeutic effects of loaded doxycycline (DOX). Pathological tissue microarrays show an association of LDLR overexpression in human glioma tissue with patient survival.NIR irradiation treatment and magnetic resonance imaging results show that OPPD reaches the effective glioma-killing temperature in a glioma-bearing rat with a skull bone removal model and considerably reduces glioma sizes relative to the drug-loaded system without the Pep22 peptide modification and the control respectively. Thus, OPPD not only effectively targets LDLR-overexpressing glioma but also exerts a dual therapeutic effect by transporting DOX into the glioma and generating thermal effects with near-infrared irradiation to kill tumor cells. These collective findings support the utility of the novel OPPD drug-loaded system as a promising drug delivery vehicle for clinical application in glioma therapy.

Neuroendoscopic Resection of Trigeminal Schwannoma in the Pterygopalatine/Infratemporal Fossa via the Transnasal Perpendicular Plate Palatine Bone or Transnasal Maxillary Sinus Approach.

BACKGROUND: Both the pterygopalatine fossa (PPF) and the infratemporal fossa (ITF) lie outside the midline of the skull base. Lesions in the PPF or ITF include trigeminal schwannoma (trigeminal schwannoma, TS), which originates from the second or third branch of the trigeminal nerve (maxillary nerve or mandibular nerve). Due to their typically deep anatomic location, lesions in the PPF or ITF can be difficult to treat using traditional surgical approaches. In recent years, because of their advantages, which include the fact that they allow the problem to be observed close up, neuroendoscopic techniques are increasingly being applied in skull base surgery, especially in treatment of lesions around the midline of the base of the skull. This study aims to 1) evaluate the neuroendoscopic treatment of lesions in PPF or ITF via the transnasal palate bone perpendicular plate or transnasal maxillary sinus approach and 2) analyze the clinical significance of this approach. METHODS: We retrospectively analyzed 3 cases of PPF TSs and 1 case of ITF TS treated between January 2015 and May 2017. All of the cases underwent neuroendoscopic resection of TSs located in the PPF via the nasal perpendicular plate palatine bone (or nasal maxillary sinus) approach. RESULTS: Two cases of PPF TSs were characterized by a thin palate bone perpendicular plate due to oppressed absorption of the tumor. Therefore the endoscopic transnasal palate bone perpendicular plate approach was employed. Additionally, 1 case of PPF TSs and 1 case of ITF TS were resected via the transnasal maxillary sinus approach. All 4 patients received total resection under endoscopy and recovered well after their respective operations without cerebrospinal fluid leakage, although 1 patient experienced postoperative dry eye symptoms and 1 other patient showed no improvement in facial numbness before and after the operation. CONCLUSIONS: Neuroendoscopic surgery performed via the transnasal perpendicular plate palatine bone or transnasal maxillary sinus approach has its own unique advantages in removing TSs in PPF and in ITF: Notably, the tumor can be exposed and dealt with under direct vision, which prevents damage to important structures, such as the internal carotid and maxillary nerves, while at the same time helping to achieve total removal of TSs. Furthermore, by adopting this approach versus traditional skull base surgery, postoperative trauma can be reduced significantly, which should be advocated for in this time of minimal invasive surgery.

Microvascular permeability of brain astrocytoma with contrast-enhanced magnetic resonance imaging: correlation analysis with histopathologic grade.

BACKGROUND: The degree of pathological microvascular proliferation is an important element in evaluation of the astrocytoma grade. This study was aimed to quantitatively assess the microvascular permeability of brain astrocytoma with the volume transfer constant (K(trans)) and volume of extravascular extracellular space per unit volume of tissue (Ve) from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and to evaluate the effectiveness of the K(trans) and Ve in the grading of astrocytoma. METHODS: The highest values of the K(trans) and Ve of 67 patients with astrocytoma (27 with grade II, 12 with grade III, and 28 with grade IV) were obtained. The comparisons of the differences of the K(trans) and Ve between the different grades were conducted using the Mann-Whitney rank-sum tests. Spearman's rank correlation coefficients were determined between K(trans) values, Ve values and astrocytoma grades. Receiver operating characteristic (ROC) curve analyses were performed to determine the cut-off values for the K(trans) and Ve to distinguish between the different grades of astrocytoma. RESULTS: There were significant differences (P < 0.001) between the different grades in the K(trans) values and Ve values, except for grades III and IV. The K(trans) values and Ve values were both correlated with astrocytoma grades (both P < 0.001). The ROC curve analyses showed that the cut-off values for the K(trans) and Ve provided the best combination of sensitivity and specificity in distinguishing between grade II and grade III or IV astrocytomas. CONCLUSIONS: DCE-MRI can play an important role in assessing the microvascular permeability and the grading of brain astrocytoma.

Low-grade and anaplastic oligodendrogliomas: differences in tumour microvascular permeability evaluated with dynamic contrast-enhanced magnetic resonance imaging.

This study was designed to quantitatively assess the microvascular permeability of oligodendroglioma using the volume transfer constant (K(trans)) and the volume of the extravascular extracellular space per unit volume of tissue (V(e)) with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). We aimed to evaluate the effectiveness of K(trans) and V(e) in distinguishing between low-grade and anaplastic oligodendroglioma. The maximal values of K(trans) and V(e) for 65 patients with oligodendroglioma (27 grade II, 38 grade III) were obtained. Differences in K(trans) and V(e) between the two groups were analysed using the Mann-Whitney rank-sum test. Receiver operating characteristic (ROC) curve analyses were performed to determine the cut-off values for the K(trans) and Ve that could differentiate between low-grade and anaplastic oligodendrogliomas. Values for K(trans) and Ve in low-grade oligodendrogliomas were significantly lower than those in anaplastic oligodendrogliomas (p < 0.001 and p < 0.001, respectively). ROC curve analysis showed that cut-off values of the K(trans) (0.037 min(-1)) and Ve (0.079) could be used to distinguish between low-grade and anaplastic oligodendrogliomas in a statistically significant manner. Our results suggest that DCE-MRI can distinguish the differences in microvascular permeability between low-grade and anaplastic oligodendrogliomas.

Quantitative analysis of neovascular permeability in glioma by dynamic contrast-enhanced MR imaging.

This study was designed to quantitatively analyse neovascular permeability in glioma by dynamic contrast-enhanced MRI (DCE-MRI). Forty-four patients with glioma were included in this study. The highest value of volume transfer constant (K(trans)) and volume of extravascular extracellular space per unit volume of tissue (V(e)) were obtained and the differences in K(trans) and V(e) between low-grade glioma (LGG) and high-grade glioma (HGG) were analyzed. The correlations between K(trans), V(e) and glioma grade were performed. Receiver operating characteristic (ROC) curve analyses were conducted. The values of K(trans) and V(e) of LGG were significantly lower than those of HGG. The correlation analysis demonstrated statistically significant relationships between K(trans) and glioma grade, between V(e) and glioma grade, and between K(trans) and V(e). The ROC curve analyses of K(trans) (0.035/min) and V(e) (0.130) for differentiating LGG from HGG were statistically significant. Thus, DCE-MRI can be used to estimate neovascular permeability and for pre-operative grading of glioma.

[Kinematics of the triangular fibrocartilage complex during forearm rotation in vivo].

OBJECTIVE: To investigate three-dimensional kinematics of the superficial and deep portion of triangular fibrocartilage complex (TFCC) in different parts of the forearm rotation. METHODS: Six wrists of 6 volunteers were used to obtain CT scans at different positions of the wrist. The wrists were scanned from 90 degrees of pronation to 90 degrees of supination at an interval of 30 degrees. The 3-dimensional radius and ulna were reconstructed with customized software and changes in length of the superficial and deep portion of TFCC during forearm rotation. RESULTS: In forearm pronation, the superficial dorsal portion and the deep palmar portion of the TFCC were tight. While the superficial palmar portion and the deep dorsal potion of the TFCC were lax. In supination, the changes in length of all these fibers were reverse. CONCLUSIONS: In forearm rotation one portion fibers of dorsal TFCC and one portion fibers of palmar TFCC are tight, and this mechanism controls stability during DRUJ rotation.

[Application of apparent diffusion coefficient and fractional anisotropy in identification of tumor component and grading of brain astrocytoma].

OBJECTIVE: To evaluate the value of apparent diffusion coefficient (ADC) and fractional anisotropy (FA) in identification of tumor element and grading of brain astrocytoma. METHODS: Thirty-three patients with histologically confirmed astrocytoma underwent diffusion weighted imaging (DWI), diffusion tensor imaging (DTI), and conventional MRI before operation. The values of ADC and FA of different regions in the same tumor and of astrocytoma of different grades were measured and compared. RESULTS: The ADC values of the tumor parenchyma, necrotic region, peritumoral edema region were (1.28 +/- 0.44), (1.97 +/- 0.53), and (1.74 +/- 0.47) respectively, all significantly higher than that of the corresponding normal brain tissues [(0.80 +/- 0.18), P = 0.009, P = 0.000, P = 0.000] with significantly differences between the tumor parenchyma and necrotic region and peritumoral edema region (both P < 0.05), however, there was not significant difference between the necrotic region and peritumoral edema region. The FA values of the tumor parenchyma, necrotic region, and peritumoral edema region were (0.18 +/- 0.07), (0.14 +/- 0.05), and (0.16 +/- 0.05) respectively, all significantly higher than that of the corresponding normal brain tissues [(0.58 +/- 0.10), all P = 0.000], without significant differences among the former 3 groups. There were no significant differences in the ADC and FA values among the tumors at different grades, however, there was a tendency of ADC to decrease and of FA to increase along the increase of grade of tumor, although not significantly. CONCLUSION: ADC value plays an important part in distinguishing tumor components and determining tumor boundary, and plays a certain role in judging the grade of astrocytomas. FA value is vital to determine the tumor boundary, and has certain value in differentiating high-grade from low-grade astrocytomas.