Neuromelanin-sensitive MRI of the substantia nigra distinguishes bipolar from unipolar depression.

Depression in bipolar disorder (BD-II) is frequently misdiagnosed as unipolar depression (UD) leading to inappropriate treatment and downstream complications for many bipolar sufferers. In this study, we evaluated whether neuromelanin-MR signal and volume changes in the substantia nigra (SN) can be used as potential biomarkers to differentiate BD-II from UD. The signal intensities and volumes of the SN regions were measured, and contrast-to-noise ratio (CNR) to the decussation of the superior cerebellar peduncles were calculated and compared between healthy controls (HC), BD-II and UD subjects. Results showed that compare to HC, both BD-II and UD subjects had significantly decreased CNR and increased volume on the right and left sides. Moreover, the volume in BD-II group was significantly increased compared to UD group. The area under the receiver operating characteristic curve (AUC) for discriminating BD from HC was the largest for the Volume-L (AUC, 0.85; 95% confidence interval [CI]: 0.77, 0.93). The AUC for discriminating UD from HC was the largest for the Volume-L (AUC, 0.76; 95% CI: 0.65, 0.86). Furthermore, the AUC for discriminating BD from UD was the largest for the Volume-R (AUC, 0.73; 95% CI: 0.62, 0.84). Our findings suggest that neuromelanin-sensitive magnetic resonance imaging techniques can be used to differentiate BD-II from UD.

Targeted nanotheranostics for the treatment of epilepsy through in vivo hijacking of locally activated macrophages.

Epilepsy refers to a disabling neurological disorder featured by the long-term and unpredictable occurrence of seizures owing to abnormal excessive neuronal electrical activity and is closely linked to unresolved inflammation, oxidative stress, and hypoxia. The difficulty of accurate localization and targeted drug delivery to the lesion hinders the effective treatment of this disease. The locally activated inflammatory cells in the epileptogenic region offer a new opportunity for drug delivery to the lesion. In this work, CD163-positive macrophages in the epileptogenic region were first harnessed as Trojan horses after being hijacked by targeted albumin manganese dioxide nanoparticles, which effectively penetrated the brain endothelial barrier and delivered multifunctional nanomedicines to the epileptic foci. Hence, accumulative nanoparticles empowered the visualization of the epileptogenic lesion through microenvironment-responsive MR T1-weight imaging of manganese dioxide. Besides, these manganese-based nanomaterials played a pivotal role in shielding neurons from cell apoptosis mediated by oxidative stress and hypoxia. Taken together, the present study provides an up-to-date approach for integrated diagnosis and treatment of epilepsy and other hypoxia-associated inflammatory diseases. STATEMENT OF SIGNIFICANCE: The therapeutic effects of antiepileptic drugs (AEDs) are hindered by insufficient drug accumulation in the epileptic site. Herein, we report an efficient strategy to use locally activated macrophages as carriers to deliver multifunctional nanoparticles to the brain lesion. As MR-responsive T1 contrast agents, multifunctional BMC nanoparticles can be harnessed to accurately localize the epileptogenic region with high sensitivity and specificity. Meanwhile, catalytic nanoparticles BMC can synergistically scavenge ROS, generate O2 and regulate neuroinflammation for the protection of neurons in the brain.

Longitudinal alterations of modular functional-metabolic coupling in first-episode schizophrenia.

Altered network organization and aberrant neurometabolic levels have been associated with schizophrenia. However, modular alterations of functional-neurometabolic coupling in various stages of schizophrenia remain unclear. This longitudinal study enrolled 34 drug-naïve first-episode schizophrenia (FES) patients and 30 healthy controls (HC). The FES patients underwent resting-state functional magnetic resonance imaging (rs-fMRI) and proton magnetic resonance spectroscopy (1H-MRS) at baseline, 2 months, and 6 months of treatment. For 1H-MRS, the concentrations of γ-aminobutyric acid (GABA), N-acetylaspartate (NAA) and glutamate + glutamine in the ventromedial prefrontal cortex region were measured. A graph theoretical approach was applied for functional connectivity-based modular parcellation. We found that intra-default mode network (DMN) connectivity, inter-modular connectivity between the DMN and the hippocampus, and inter-modular connectivity between the DMN and the frontoparietal module were significantly different across 6-month treatment in the FES patients. The inter-module connectivity of the DMN and hippocampus correlated positively with NAA concentration in the HC group, while this correlation was absent in FES patients. This exploratory study suggests an altered modular connectivity in association with neurometabolite concentrations in FES patients and provides insights into multimodal neuroimaging biomarkers in schizophrenia. Future studies with larger sample sizes are needed to consolidate our findings.

Perfluorooctyl bromide nanoemulsions holding MnO2 nanoparticles with dual-modality imaging and glutathione depletion enhanced HIFU-eliciting tumor immunogenic cell death.

Tumor-targeted immunotherapy is a remarkable breakthrough, offering the inimitable advantage of specific tumoricidal effects with reduced immune-associated cytotoxicity. However, existing platforms suffer from low efficacy, inability to induce strong immunogenic cell death (ICD), and restrained capacity of transforming immune-deserted tumors into immune-cultivated ones. Here, an innovative platform, perfluorooctyl bromide (PFOB) nanoemulsions holding MnO2 nanoparticles (MBP), was developed to orchestrate cancer immunotherapy, serving as a theranostic nanoagent for MRI/CT dual-modality imaging and advanced ICD. By simultaneously depleting the GSH and eliciting the ICD effect via high-intensity focused ultrasound (HIFU) therapy, the MBP nanomedicine can regulate the tumor immune microenvironment by inducing maturation of dendritic cells (DCs) and facilitating the activation of CD8+ and CD4+ T cells. The synergistic GSH depletion and HIFU ablation also amplify the inhibition of tumor growth and lung metastasis. Together, these findings inaugurate a new strategy of tumor-targeted immunotherapy, realizing a novel therapeutics paradigm with great clinical significance.

Conventional, diffusion, and dynamic contrast-enhanced MRI findings for differentiating metaplastic Warthin's tumor of the parotid gland.

The purpose of this study was to explore conventional, diffusion, and dynamic contrast-enhanced MRI (DCE-MRI) characteristics for differentiating metaplastic Warthin's tumor (MWT) from other tumor types of the parotid gland, including non-metaplastic Warthin's tumor (non-MWT), pleomorphic adenoma (PA), and malignant tumor (MT). A total of 178 patients with histologically proven tumors of the parotid gland, including 21 MWTs, 49 non-MWTs, 66 PAs, and 42 MTs, were enrolled in the study. Conventional MRI was performed in all patients. One hundred and fifty patients had preoperative diffusion-weighted MR imaging (DWI), and 62 patients had preoperative DCE-MRI. The differences in the conventional, DCE-MRI, and DWI records between MWTs and the other three tumor types were statistically evaluated. Compared with non-MWTs and PAs, there was a statistically significant difference in circumscription (p < 0.01). The ill-defined circumscription was more common in MWTs than non-MWTs and PAs. Compared with PAs, there was a statistically significant difference in morphology (p < 0.05). The lobulated morphology was more common in PAs than MWTs. Compared with PAs and MTs, there was a statistically significant difference in the T2 signal of the solid component (p < 0.01). The T2 moderate intensity of solid components was more common in MWTs than PAs and MTs. The solid components of PAs mostly showed hyperintense on T2-weighted imaging. Cyst/necrosis was more common in MWTs than PAs and MTs. Hyperintense of cyst/necrosis was more common in MWTs and non-MWTs. With respect to contrast enhancement, 52.4% MWTs exhibited moderate or marked enhancement, and most non-MWTs (81.6%) exhibited mild enhancement. Most PAs (84.8%) exhibited marked enhancement. The mean ADC value of MWTs (0.94 × 10-3 ± 0.11 mm2/s) was significantly lower than that of the PAs (1.60 × 10-3 ± 0.17 mm2/s) (p < 0.001). On DCE-MRI, six of eight MWTs demonstrated TIC of type B. Although MWT is rare, conventional MRI characteristics, DWI and DCE-MRI can provide useful information for differentiating MWT from other parotid mass.

MRI Features of Intracranial Anaplastic Ependymomas: A Comparison of Supratentorial and Infratentorial Lesions.

Background: Several previous reports of anaplastic ependymomas have described their imaging features, and most of these studies were case reports. However, no studies have compared the magnetic resonance imaging (MRI) features between the infratentorial and supratentorial anaplastic ependymomas. Objective: The goal of this study was to explore MRI characteristics for intracranial anaplastic ependymomas. Material and Methods: We retrospectively reviewed the demographics of 165 patients and MRI findings of 60 patients with supratentorial (SAEs) and infratentorial anaplastic ependymomas (IAEs) before surgery. The demographics and MRI features for SAEs and IAEs were compared and evaluated. Results: Among the 60 patients, most SAEs (91.7%) were extraventricular, whereas most IAEs (91.7%) were intraventricular. Of sixty intracranial anaplastic ependymomas, most lesions were well-defined (n = 45) and round-like (n = 36). On T1-weighted imaging, compared with the gray matter, the SAEs exhibited heterogeneous signal intensity, whereas IAEs exhibited iso-hypointense signals. T2 signals exhibited greater associations with hyperintense signals in IAEs; however, SAEs showed hyperintense or hypointense-hyperintense. On diffusion-weighted imaging (DWI), almost all solid tissues of SAEs appeared as hyperintense, whereas IAEs exhibited iso-hypointense signals. Peritumoral edema and intratumoral hemorrhage occurred more frequently in SAEs. Almost all anaplastic ependymomas exhibited heterogeneous enhancement. Cysts or necrosis was associated with 56 anaplastic ependymomas; however, large cysts were more prevalent in SAEs. On magnetic resonance spectroscopy (MRS), the mean choline/creatine (Cho/Cr) and choline/N-acetyl-aspartate (Cho/NAA) ratio of anaplastic ependymomas were (6.58 ± 4.26) and (8.84 ± 6.34), respectively, representing typical high-grade tumors. Conclusion: We demonstrate the conventional and functional MRI features of intracranial anaplastic ependymomas, including DWI and MRS. MRI characteristics, such as location, cyst, diffusion restriction, and peritumoral edema, differed between supratentorial and infratentorial locations. Cho/Cr and Cho/ NAA ratios of anaplastic ependymomas are increased.

Presurgical differentiation between malignant haemangiopericytoma and angiomatous meningioma by a radiomics approach based on texture analysis.

PURPOSE: To assess whether a machine-learning model based on texture analysis (TA) could yield a more accurate diagnosis in differentiating malignant haemangiopericytoma (HPC) from angiomatous meningioma (AM). MATERIALS AND METHODS: Sixty-seven pathologically confirmed cases, including 24 malignant HPCs and 43 AMs between May 2013 and September 2017 were retrospectively reviewed. In each case, 498 radiomic features, including 12 clinical features and 486 texture features from MRI sequences (T2-FLAIR, DWI and enhanced T1WI), were extracted. Three neuroradiologists independently made diagnoses by vision. Four Support Vector Machine (SVM) classifiers were built, one based on clinical features and three based on texture features from three MRI sequences after feature selection. The diagnostic abilities of these classifiers and three neuroradiologists were evaluated by receiver operating characteristic (ROC) analysis. RESULTS: Malignant HPCs were found to have larger sizes, slighter degrees of peritumoural oedema compared with AMs (P<0.05), and more serpentine-like vessels. The AUC of the enhanced T1WI-based classifier was 0.90, significantly higher than that of T2-FLAIR-based or DWI-based classifiers (0.77 and 0.73). The AUC of the SVM classifier based on clinical features was 0.66, slightly but not significantly lower than the performances of 3 neuroradiologists (AUC=0.69, 0.70 and 0.73). CONCLUSION: Machine-learning models based on clinical features alone could not provide a better diagnostic performance than that of radiologists. The SVM classifier built by texture features extracted from enhanced T1WI is a promising tool to differentiate malignant HPC from AM before surgery.

Role of quantitative analysis of T2 relaxation time in differentiating benign from malignant breast lesions.

Objective To investigate the role of quantitative analysis of T2 relaxation time in the magnetic resonance imaging (MRI) diagnosis of breast cancer. Methods The study enrolled patients with clinical breast masses who were examined using MRI at eight different echo times. The differences in T2 relaxation time of benign and malignant breast lesions were analysed. Results A total of 67 patients (67 breast lesions: 46 malignant, 21 benign) were examined. The mean ± SD T2 relaxation time was significantly lower in the 46 malignant lesions compared with the 21 benign lesions (82.69 ± 15.37 ms versus 95.48 ± 26.51 ms, respectively). The area under the curve was 0.731. Using 79.52 ms as the cut-off between benign and malignant breast lesions, a sensitivity of 85.7% and a specificity of 58.7% were obtained. Conclusions There was a significant difference in T2 relaxation time between benign and malignant breast lesions. The specificity of using T2 relaxation time alone for the differentiation of benign from malignant lesions was not high, but it could constitute a new adjunct in the MRI diagnosis of breast cancer.

Enhanced photothermal therapy of biomimetic polypyrrole nanoparticles through improving blood flow perfusion.

In this study, we reported a strategy to improve delivery efficiency of a long-circulation biomimetic photothermal nanoagent for enhanced photothermal therapy through selectively dilating tumor vasculature. By using a simply nanocoating technology, a biomimetic layer of natural red blood cell (RBC) membranes was camouflaged on the surface of photothermal polypyrrole nanoparticles (PPy@RBC NPs). The erythrocyte-mimicking PPy NPs inherited the immune evasion ability from natural RBC resulting in superior prolonged blood retention time. Additionally, excellent photothermal and photoacoustic imaging functionalities were all retained attributing to PPy NPs cores. To further improve the photothermal outcome, the endothelin A (ETA) receptor antagonist BQ123 was jointly employed to regulate tumor microenvironment. The BQ123 could induce tumor vascular relaxation and increase blood flow perfusion through modulating an ET-1/ETA transduction pathway and blocking the ETA receptor, whereas the vessel perfusion of normal tissues was not altered. Through our well-designed tactic, the concentration of biomimetic PPy NPs in tumor site was significantly improved when administered systematically. The study documented that the antitumor efficiency of biomimetic PPy NPs combined with specific antagonist BQ123 was particularly prominent and was superior to biomimetic PPy NPs (P < 0.05) and PEGylated PPy NPs with BQ123 (P < 0.01), showing that the greatly enhanced photothermal treatment could be achieved with low-dose administration of photothermal agents. Our findings would provide a promising procedure for other similar enhanced photothermal treatment by blocking ETA receptor to dramatically increase the delivery of biomimetic photothermal nanomaterials.

Comparison of MRI features for the differentiation of hepatic angiomyolipoma from fat-containing hepatocellular carcinoma.

OBJECTIVE: The purpose of this study was to evaluate MRI features for the differentiation of hepatic angiomyolipoma (HAML) from fat-containing hepatocellular carcinoma. METHODS: We retrospectively reviewed the MRI findings of 20 patients with 22 hepatic angiomyolipomas and 25 patients with fat-containing hepatocellular carcinomas before surgery. The MRI features and apparent diffusion coefficient (ADC) for the two types of tumors were compared and analyzed. RESULTS: Fat was not detected in nine (40.9%) of the angiomyolipomas. An enhancement pattern of the washout area was seen in eight (36.4%) of the angiomyolipomas and 21 of the hepatocellular carcinomas (84%) (p = 0.001). The sensitivity, specificity, and accuracy of the enhancement pattern for HAML were 63.6% (14/22), 84% (21/25), and 74.5% (35/47), respectively. An early draining vein was seen in 16 (72.7%) angiomyolipomas and two hepatocellular carcinomas (8%) (p < 0.001). The sensitivity, specificity, and accuracy of an early draining vein for detecting HAML was 72.7% (16/22), 92% (23/25), and 83.0% (39/47), respectively. Tumor vessels were noted in 18 (81.8%) angiomyolipomas and six hepatocellular carcinomas (24%) (p < 0.001). The sensitivity, specificity, and accuracy of tumor vessels for HAML were 81.8% (18/22), 76% (19/25), and 78.7% (37/47), respectively. Pseudocapsules were absent in 21 (95.5%) angiomyolipomas as compared with 3 (12%) hepatocellular carcinomas (p < 0.001). The sensitivity, specificity, and accuracy of pseudocapsules for HAML were 95.5% (21/22), 88% (22/25), and 91.5% (43/47), respectively. The ADC of the angiomyolipomas (1.92 ± 0.29 × 10(-3 )mm(2)/s) was significantly higher than that for hepatocellular carcinomas (1.33 ± 0.25 × 10(-3 )mm(2)/s) (p < 0.001). CONCLUSION: The presence of an early draining vein and tumor vessels, the absence of pseudocapsules and a higher ADC in the hypervascular hepatic tumor on the MRI were helpful for the differentiation of hepatic angiomyolipoma from fat-containing hepatocellular carcinoma.

[The MRI and clinical features of acinic cell carcinoma of the parotid gland].

OBJECTIVE: To analyze the MR imaging findins of acinic cell carcinoma(ACC) in parotid gland and develop the diagnosis of this disease. METHOD: The MR imaging fearures of 11 patients with pathologically proved ACC were retrospectively analyzed. MR imagings were analyzed in relation to the follow:amount, location, size, shape, margin, pseudocapsule, MR signal intensity and enhanced pattern and the cervical lymphadenopathy. The clinical analysis on patients included age, sex, and follow-up. RESULT: There were 11 patients, 7 lesions was located in the right parotid gland and 4 lesions was located in the left parotid gland; the average maximum diameter was (2.66±0.99)cm; 7 lesions showed lobulated,and 4 lesions showed round; 8 lesions had no pseudocapsules and 3 lesions had incomplete pseudocapsule. All lesions showed homogeneous or heterogeneous isointense and slight hyperintense on T1 WI and T2WI. On post contrast images, the tumor parenchyma ingredients showed remarkable enhancement in all lesions. CONCLUSION: The MR imaging of ACC in the parotid gland don't have specific features, but when the tumor of the parotid gland showed no pseudocapsule (or showed incomplete pseudocapsule), lobulate, small cysitc and remarkable enhancement, it may indicate ACC, and the correct diagnosis depends on clinical pathology.

Comparison of lung lesion biopsies between low-dose CT-guided and conventional CT-guided techniques.

BACKGROUND: The low-dose computed tomography (CT) technique has been widely used because it decreases the potential risk of radiation exposure, as well as enabling low-dose CT-guided lung lesion biopsy. However, uncertainties remain regarding diagnostic accuracy, radiation dose, complication rate, and image quality. PURPOSE: To compare the diagnostic accuracy, radiation dose, complication rate, and image quality of lung lesion biopsy between conventional CT-guided and low-dose CT-guided techniques. MATERIAL AND METHODS: A total of 90 patients were prospectively enrolled and randomized into two groups (group A: 120 kv; 200 mA; thickness, 2.0 mm; pitch, 16 mm/rot; n = 44; group B: 120 kv;10 mA; thickness, 2.0 mm; pitch, 23 mm/rot; n = 46). Sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), radiation dose, image quality, and complication rate were compared. All variables between the two groups were analyzed using chi-square and Student's t tests. A P value of < 0.05 was considered statistically significant. RESULTS: The sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) for diagnosing lung lesions were 96.88%, 100%, 97.5%, 100%, and 88.89% in group A, respectively. In group B, the values were 96.67%, 100%, 97.5%, 100%, and 90.91%, respectively (P > 0.05). The mean weighted CT dose index (CTDIw) and dose-length product (DLP) were 29.29 ± 3.93 mGy and 211.74 ± 37.89 mGy*cm in group A and 1.55 ± 0.15 mGy and 10.98 ± 1.56 mGy*cm in group B (P < 0.001). Image quality satisfied the need for a coaxial biopsy. Complications in group A and group B were observed in 27.28% and 23.91% of the patients, respectively (P > 0.05). CONCLUSION: Compared to conventional CT-guided biopsies, lung lesion biopsies guided by the low-dose CT biopsy protocol showed dramatically lower CTDIw and DLP levels. In contrast, the diagnostic yield of the procedures did not differ significantly, which is a recommended technique in certain populations.

Assessment of dynamic contrast-enhanced magnetic resonance imaging in the differentiation of malignant from benign orbital masses.

OBJECTIVE: Dynamic contrast enhanced MR imaging (DCE-MRI) allows imaging of the physiology of the microcirculation. The purpose of this study was to determine the diagnostic efficacy of time intensity curve (TIC) and DCE parameters for characterization of orbital masses. METHODS: Fifty-nine patients with untreated orbital lesions underwent DCE-MRI before surgery. For each lesion, peak height (PH), maximum enhancement ratio (ERmax), time of peak enhancement (Tpeak) and maximum rise slope (Slopemax) were plotted and calculated. Receiver operator characteristics (ROC) analysis was conducted to assess the appropriate cut-off value. RESULTS: All 26 lesions that demonstrated persistent pattern (type-I) TICs were benign. Most of the masses with the washout pattern (type-III) TIC were malignant (10/14), including lymphoma (n=6) and melanoma (n=4). The Slopemax of benign lesions was statistically lower than malignant ones, while the ERmax and Tpeak values of benign lesions were significantly higher. No statistical difference was found in PH (P=0.121). The AUC for ERmax, Tpeak and Slopemax in differentiating benign orbital lesions from malignant ones were 0.683, 0.837 and 0.738, respectively. In the three DCE parameters, Slopemax cut-off value of 1.10 provided the highest sensitivity of 93.8%; however, the corresponding specificity was low (58.1%). The ERmax cut-off value of 1.37 and Tpeak cut-off value of 35.14 respectively offered the best diagnostic performances. CONCLUSION: DCE-MRI, especially the qualitative TIC pattern and quantitative value of Slopemax, ERmax and Tpeak, could be a complementary investigation in distinguishing malignant orbital tumor from benign ones.