Effects of APOE ε2 allele on basal forebrain functional connectivity in mild cognitive impairment.

BACKGROUND: Basal forebrain cholinergic system (BFCS) dysfunction is associated with cognitive decline in Alzheimer's disease (AD) and mild cognitive impairment (MCI). Apolipoprotein E (APOE) ε2 is a protective genetic factor in AD and MCI, and cholinergic sprouting depends on APOE. OBJECTIVE: We investigated the effect of the APOE ε2 allele on BFCS functional connectivity (FC) in cognitively normal (CN) subjects and MCI patients. METHOD: We included 60 MCI patients with APOE ε3/ε3, 18 MCI patients with APOE ε2/ε3, 73 CN subjects with APOE ε3/ε3, and 36 CN subjects with APOE ε2/ε3 genotypes who had resting-state functional magnetic resonance imaging data from the Alzheimer's disease Neuroimaging Initiative. We used BFCS subregions (Ch1-3 and Ch4) as seeds and calculated the FC with other brain areas. Using a mixed-effect analysis, we explored the interaction effects of APOE ε2 allele × cognitive status on BFCS-FC. Furthermore, we examined the relationships between imaging metrics, cognitive abilities, and AD pathology markers, controlling for sex, age, and education as covariates. RESULTS: An interaction effect on functional connectivity was found between the right Ch4 (RCh4) and left insula (p < 0.05, corrected), and between the RCh4 and left Rolandic operculum (p < 0.05, corrected). Among all subjects and APOE ε2 carriers, RCh4-left Insula FC was associated with early tau deposition. Furthermore, no correlation was found between imaging metrics and amyloid burden. Among all subjects and APOE ε2 carriers, FC metrics were associated with cognitive performance. CONCLUSION: The APOE ε2 genotype may play a protective role during BFCS degeneration in MCI.

Different patterns of exosomal α-synuclein between Parkinson's disease and probable rapid eye movement sleep behavior disorder.

BACKGROUND AND PURPOSE: The insidious onset of Parkinson's disease (PD) makes early diagnosis difficult. Notably, idiopathic rapid eye movement sleep behavior disorder (iRBD) was reported as a prodrome of PD, which may represent a breakthrough for the early diagnosis of PD. However, currently there is no reliable biomarker for PD diagnosis. Considering that α-synuclein (α-Syn) and neuroinflammation are known to develop prior to the onset of clinical symptoms in PD, it was hypothesized that plasma total exosomal α-Syn (t-exo α-Syn), neural-derived exosomal α-Syn (n-exo α-Syn) and exosomal apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC) may be potential biomarkers of PD. METHODS: In this study, 78 PD patients, 153 probable iRBD patients (pRBD) and 63 healthy controls (HCs) were recruited. α-Syn concentrations were measured using a one-step paramagnetic particle-based chemiluminescence immunoassay, and ASC levels were measured using the Ella system. RESULTS: It was found that t-exo α-Syn was significantly increased in the PD group compared to the pRBD and HC groups (p < 0.0001), whilst n-exo α-Syn levels were significantly increased in both the PD and pRBD groups compared to HCs (p < 0.0001). Furthermore, although no difference was found in ASC levels between the PD and pRBD groups, there was a positive correlation between ASC and α-Syn in exosomes. CONCLUSIONS: Our results suggest that both t-exo α-Syn and n-exo α-Syn were elevated in the PD group, whilst only n-exo α-Syn was elevated in the pRBD group. Additionally, the adaptor protein of inflammasome ASC is correlated with α-Syn and may facilitate synucleinopathy.

A multiple-tissue-specific magnetic resonance imaging model for diagnosing Parkinson's disease: a brain radiomics study.

Brain radiomics can reflect the characteristics of brain pathophysiology. However, the value of T1-weighted images, quantitative susceptibility mapping, and R2* mapping in the diagnosis of Parkinson's disease (PD) was underestimated in previous studies. In this prospective study to establish a model for PD diagnosis based on brain imaging information, we collected high-resolution T1-weighted images, R2* mapping, and quantitative susceptibility imaging data from 171 patients with PD and 179 healthy controls recruited from August 2014 to August 2019. According to the inclusion time, 123 PD patients and 121 healthy controls were assigned to train the diagnostic model, while the remaining 106 subjects were assigned to the external validation dataset. We extracted 1408 radiomics features, and then used data-driven feature selection to identify informative features that were significant for discriminating patients with PD from normal controls on the training dataset. The informative features so identified were then used to construct a diagnostic model for PD. The constructed model contained 36 informative radiomics features, mainly representing abnormal subcortical iron distribution (especially in the substantia nigra), structural disorganization (e.g., in the inferior temporal, paracentral, precuneus, insula, and precentral gyri), and texture misalignment in the subcortical nuclei (e.g., caudate, globus pallidus, and thalamus). The predictive accuracy of the established model was 81.1 ± 8.0% in the training dataset. On the external validation dataset, the established model showed predictive accuracy of 78.5 ± 2.1%. In the tests of identifying early and drug-naïve PD patients from healthy controls, the accuracies of the model constructed on the same 36 informative features were 80.3 ± 7.1% and 79.1 ± 6.5%, respectively, while the accuracies were 80.4 ± 6.3% and 82.9 ± 5.8% for diagnosing middle-to-late PD and those receiving drug management, respectively. The accuracies for predicting tremor-dominant and non-tremor-dominant PD were 79.8 ± 6.9% and 79.1 ± 6.5%, respectively. In conclusion, the multiple-tissue-specific brain radiomics model constructed from magnetic resonance imaging has the ability to discriminate PD and exhibits the advantages for improving PD diagnosis.

Characterizing mild cognitive impairment in prodromal Parkinson's disease: A community-based study in China.

OBJECTIVE: The International Parkinson and Movement Disorder Society (MDS) has published research criteria for prodromal Parkinson's disease (pPD), which includes cognitive impairment as a prodromal marker. However, the clinical features of mild cognitive impairment (MCI) in pPD remain unknown. Our study aimed to evaluate the frequency and clinical features of mild cognitive impairment of pPD in the elderly in China. METHODS: The cross-sectional community-based study recruited 2688 participants aged ≥50 years. Subjects were diagnosed with pPD according to the MDS criteria. Overall, 39 pPD and 22 healthy controls underwent comprehensive clinical and neuropsychological assessment. MCI was also diagnosed by the MDS criteria. Next, we investigated the relationship between clinical factors and cognition. RESULTS: Among the 2,663 dementia-free and Parkinson disease (PD)-free participants, 55 met the criteria for pPD (2.1%) and 23 pPD met the criteria for MCI. Memory, attention/working memory, and executive function were the most frequent impaired domains, and amnestic MCI multidomain phenotype was the most frequent MCI subtype (69.57%) in pPD. Additionally, correlation analysis revealed that the global cognitive performance was negatively related to UPDRS-III score (r = -0.456, p = 0.004). CONCLUSION: MCI, specifically impairment in memory, attention/working memory, and executive domain, is present at the prodromal stage of PD. In addition, cognitive performance is correlated with motor symptoms in pPD. Our results reflect that cognitive profile, combined with motor symptoms, can help clinicians to identify individuals with pPD early, as those would be the optimal candidates for neuroprotective therapy.

High-resolution computed tomography findings independently predict epidermal growth factor receptor mutation status in ground-glass nodular lung adenocarcinoma.

BACKGROUND: For lung adenocarcinoma with epidermal growth factor receptor (EGFR) gene mutation, small molecule tyrosine kinase inhibitors are more effective. Some patients could not obtain enough histological specimens for EGFR gene mutation detection. Specific imaging features can predict EGFR mutation status to a certain extent. AIM: To assess the associations of EGFR mutations with high-resolution computerized tomography (HRCT) features in ground-glass nodular lung adenocarcinoma. METHODS: This study retrospectively assessed patients with ground-glass nodular lung adenocarcinoma diagnosed between January 2011 and March 2017. EGFR gene mutations in exons 18-21 were detected. The patients were classified into mutant EGFR and wild-type groups, and general data and HRCT image characteristics were assessed. RESULTS: Among 98 patients, 31 (31.6%) and 67 (68.4%) had mutated and wild-type EGFR in exons 18-21, respectively. Gender, age, smoking history, location of lesions, morphology, edges, borders, pleural indentations, and associations of nodules with bronchus and blood vessels were comparable in both groups (all P > 0.05). Patients with mutant EGFR had larger nodules than those with the wild-type (17.19 ± 6.79 and 14.37 ± 6.30 mm, respectively; P = 0.047). Meanwhile, the vacuole/honeycomb sign was more frequent in the mutant EGFR group (P = 0.011). The logistic regression prediction model included the combination of nodule size and vacuole/honeycomb sign (OR = 1.120, 95%CI: 1.023-1.227, P = 0.014) revealed a sensitivity of 83.9%, a specificity of 52.2% and an AUC of 0.698 (95%CI: 0.589-0.806; P = 0.002). CONCLUSION: Nodule size and vacuole/honeycomb features could independently predict EGFR mutation status in ground-glass nodular lung adenocarcinoma.

Cardiorespiratory arrest after iso-osmolar iodinated contrast injection: A case report of contrast-induced encephalopathy following contrast-enhanced computed-tomography.

RATIONALE: Contrast-induced encephalopathy (CIE) is a rare complication caused by administration of intravascular contrast media and characterized by acute reversible neurological disturbance. Most of the CIE cases are reported after arterial administration of contrast media such as during cerebral or coronary angiographies, yet only a few articles have reported CIE secondary to intravenous contrast. A case of CIE secondary to intravenous contrast administration is reported here. PATIENT CONCERNS: A 68-year-old man was admitted to our hospital for contrast-enhanced chest computed-tomography (CT) examination due to suspected pulmonary nodules. After CT examination, the patient lost consciousness and experienced a cardiorespiratory arrest. An emergency plain brain CT was done immediately which showed abnormal cortical contrast enhancement and cerebral sulci hyperdensity. DIAGNOSES: After excluding other differential diagnoses such as electrolytes imbalance, hypo/hyperglycemia, cardiogenic pathologies and other neurological emergencies such as cerebral hemorrhage, cerebral infarction, the final diagnosis of CIE was made. INTERVENTIONS: The patient was admitted to the intensive care unit for further management. A series of supportive treatments were arranged. OUTCOMES: Follow-up visits at the outpatient clinic showed no lasting neurological deficits. LESSONS: CIE should be considered as 1 of the differential diagnoses for a patient with acute neurologic symptoms after iodinate contrast administration. Neuroradiological imaging examinations are essential to rule out other etiologies such as acute cerebral infarction or intracranial hemorrhage.

Progressive brain atrophy in Parkinson's disease patients who convert to mild cognitive impairment.

AIMS: Cognitive impairment is a common symptom in the trajectory of Parkinson's disease (PD). However, the pathological underpinning is not fully known. We aimed to explore the critical structural alterations in the process of cognitive decline and its relationships with the dopaminergic deficit and the level of related cerebrospinal fluid (CSF) proteins. METHODS: Ninety-four patients with PD and 32 controls were included in this study. Neuropsychological tests were performed at baseline and after 28 months to identify which patients had normal cognition and which ones developed PD-MCI after follow-up ("converters"). Gray matter atrophy was assessed in cross-sectional and longitudinal analyses, respectively. The associations between altered GMV with dopamine transporter (DAT) results and the level of CSF proteins were assessed. RESULTS: Among the 94 patients with normal cognition at baseline, 24 (mean age, 63.1 years) developed PD-MCI after 28 months of follow-up, and 70 (mean age, 62.3 years) remained nonconverters. The converters showed significant right temporal atrophy at baseline and extensive atrophy in temporal lobe at follow-up. Progressive bilateral frontal lobe atrophy was found in the converters. Baseline right temporal atrophy was correlated with the striatal dopaminergic degeneration in the converters. No correlation was found between the right temporal atrophy and the alterations of CSF proteins. CONCLUSION: Early atrophy in temporal lobes and progressive atrophy in frontal lobes might be a biomarker for developing multidomain impairment of cognition and converting to PD-MCI. Furthermore, cognition-related temporal atrophy might be associated with dopaminergic deficit reflected by DAT scan but independent of CSF proteins in patients with PD who convert to PD-MCI.

Oscillation-specific nodal alterations in early to middle stages Parkinson's disease.

BACKGROUND: Different oscillations of brain networks could carry different dimensions of brain integration. We aimed to investigate oscillation-specific nodal alterations in patients with Parkinson's disease (PD) across early stage to middle stage by using graph theory-based analysis. METHODS: Eighty-eight PD patients including 39 PD patients in the early stage (EPD) and 49 patients in the middle stage (MPD) and 36 controls were recruited in the present study. Graph theory-based network analyses from three oscillation frequencies (slow-5: 0.01-0.027 Hz; slow-4: 0.027-0.073 Hz; slow-3: 0.073-0.198 Hz) were analyzed. Nodal metrics (e.g. nodal degree centrality, betweenness centrality and nodal efficiency) were calculated. RESULTS: Our results showed that (1) a divergent effect of oscillation frequencies on nodal metrics, especially on nodal degree centrality and nodal efficiency, that the anteroventral neocortex and subcortex had high nodal metrics within low oscillation frequencies while the posterolateral neocortex had high values within the relative high oscillation frequency was observed, which visually showed that network was perturbed in PD; (2) PD patients in early stage relatively preserved nodal properties while MPD patients showed widespread abnormalities, which was consistently detected within all three oscillation frequencies; (3) the involvement of basal ganglia could be specifically observed within slow-5 oscillation frequency in MPD patients; (4) logistic regression and receiver operating characteristic curve analyses demonstrated that some of those oscillation-specific nodal alterations had the ability to well discriminate PD patients from controls or MPD from EPD patients at the individual level; (5) occipital disruption within high frequency (slow-3) made a significant influence on motor impairment which was dominated by akinesia and rigidity. CONCLUSIONS: Coupling various oscillations could provide potentially useful information for large-scale network and progressive oscillation-specific nodal alterations were observed in PD patients across early to middle stages.

Whole-tumor perfusion CT using texture analysis in unresectable stage IIIA/B non-small cell lung cancer treated with recombinant human endostatin.

BACKGROUND: To observe the dynamic changes of blood perfusion with whole-tumor computed tomography (CT) perfusion imaging using texture analysis in patients with unresectable stage IIIA/B non-small cell lung cancer (NSCLC) treated with recombinant human endostatin (Endostar). METHODS: This phase II clinical trial recruited 11 patients diagnosed with stage IIIA/B NSCLC. Histological examination prior to treatment revealed squamous cell carcinoma in 4 cases and adenocarcinoma in 7 cases. All patients underwent contrast-enhanced perfusion CT at baseline and a second CT scan 1 week after treatment initiation with Endostar. CT perfusion images including blood flow (BF), blood volume (BV), and permeability (PMB) were imported into OmniKinetics software to quantitatively assess the texture features. Skewness, kurtosis, and entropy were calculated at baseline and after anti-angiogenic therapy. Changes in tumor were analyzed using Wilcoxon signed-rank test. The association of parameters with survival was evaluated using Cox proportional hazards regression model. RESULTS: There were no statistical differences in the mean values of BF, BV, and PMB before and after treatment (P=0.594, 0.477 and 0.328, respectively). The skewness on BF images demonstrated significant differences at baseline and after treatment (0.6±2.7 vs. 1.0±2.6, P=0.010), while skewness of BV and PMB showed no significant variation (P=0.477 and 0.213, respectively). The kurtosis and entropy for BF, BV and PMB showed no significant differences (all P>0.05). In adenocarcinoma, the mean BF showed no significant differences at baseline and after treatment (76.5±25.7 vs. 101.2±46.4, P=0.398), while skewness for BF was significantly higher after treatment than at baseline (-0.19±3.3 vs. 0.59±3.2, P=0.028). No significant associations were found between perfusion CT imaging parameters and progression-free survival. CONCLUSIONS: These results suggested that blood perfusion showed improvement with whole-tumor perfusion CT using texture analysis in patients with stage IIIA/B NSCLC treated by Endostar.

Radiation-induced gray matter atrophy in patients with nasopharyngeal carcinoma after intensity modulated radiotherapy: a MRI magnetic resonance imaging voxel-based morphometry study.

BACKGROUND: Gray matter (GM) damage after radiotherapy (RT) in nasopharyngeal carcinoma (NPC) patients can result in cognitive impairment, while there may be no visible brain tissue change according to the conventional magnetic resonance imaging (MRI). This study investigated radiation-induced GM volume differences between NPC patients who received RT and those who did not. METHODS: High-resolution brain structural MRI data from two groups of patients were acquired. The pre-RT group was composed of 56 newly diagnosed but not yet medically treated NPC patients, while the after-RT group consisted of 40 NPC patients who had completed RT more than 1 year ago. Voxel-based morphometry (VBM) was applied to assess GM volumes. Two sample t-test was used to analyze GM volumes voxel-by-voxel using the VBM8 toolbox built in the SPM software. Radiation-induced cortical volume alteration in all NPC patients after RT and dosimetry of 36 patients were analyzed. RESULTS: Compared to pre-treatment group, cortical volumes of GM were significantly smaller in the left hippocampus, the right pulvinar and the right middle temporal gyrus (MTG, P<0.001, AlphaSim correction, cluster size ≥157). The mean dose (Dmean) for bilateral hippocampal heads were significantly higher than other different parts of the brain (P<0.001). No significant correlations between the GM volume in any brain regions and the mean dose of corresponding position of these brain regions were observed (P>0.05). CONCLUSIONS: Radiation to the NPC patients can not only induce damage of the hippocampus, but also other secondary damages of GM.

Aberrant functional connectivity network in subjective memory complaint individuals relates to pathological biomarkers.

BACKGROUND: Individuals with subjective memory complaints (SMC) feature a higher risk of cognitive decline and clinical progression of Alzheimer's disease (AD). However, the pathological mechanism underlying SMC remains unclear. We aimed to assess the intrinsic connectivity network and its relationship with AD-related pathologies in SMC individuals. METHODS: We included 44 SMC individuals and 40 normal controls who underwent both resting-state functional MRI and positron emission tomography (PET). Based on graph theory approaches, we detected local and global functional connectivity across the whole brain by using degree centrality (DC) and eigenvector centrality (EC) respectively. Additionally, we analyzed amyloid deposition and tauopathy via florbetapir-PET imaging and cerebrospinal fluid (CSF) data. The voxel-wise two-sample T-test analysis was used to examine between-group differences in the intrinsic functional network and cerebral amyloid deposition. Then, we correlated these network metrics with pathological results. RESULTS: The SMC individuals showed higher DC in the bilateral hippocampus (HP) and left fusiform gyrus and lower DC in the inferior parietal region than controls. Across all subjects, the DC of the bilateral HP and left fusiform gyrus was positively associated with total tau and phosphorylated tau181. However, no significant between-group difference existed in EC and cerebral amyloid deposition. CONCLUSION: We found impaired local, but not global, intrinsic connectivity networks in SMC individuals. Given the relationships between DC value and tau level, we hypothesized that functional changes in SMC individuals might relate to pathological biomarkers.

Distinct Patterns of Interhemispheric Connectivity in Patients With Early- and Late-Onset Alzheimer's Disease.

Background: Early-onset Alzheimer's disease (EOAD) presents a different clinical profile than late-onset Alzheimer's disease (LOAD). Neuroimaging studies have demonstrated that patients with EOAD present more atrophy and functional disconnection than LOAD patients. However, it remains unknown whether the interhemispheric functional disconnection or its underlying structural impairment contributes to the different clinical profiles of EOAD and LOAD. Methods: According to the arbitrary cut-off age of 65, we included 22 EOAD patients, 27 LOAD patients and 38 healthy controls (further divided into 21 relatively young and 17 old controls). Participants underwent resting-state functional MRI, diffusion tensor imaging (DTI) and comprehensive neuropsychological assessments. We used voxel-mirrored homotopic connectivity (VMHC) to examine interhemispheric functional connectivity. Then, we calculated the diffusion index based on tract-based spatial statistics (TBSS). Two-sample t-tests were used to assess the interhemispheric connectivity differences between each patient group and its corresponding control group. Results: We found that the EOAD patients had lower VMHC in the hippocampus, parahippocampal gyrus (PHG), superior temporal gyrus (STG) and inferior parietal cortex (IPC) than did controls. Consistently, the EOAD patients exhibited white matter (WM) tract impairment in the posterior regions. On the other hand, the LOAD patients displayed increased VMHC and impaired WM tracts in the frontal region. Correlation analyses showed that VMHC in the IPC was related to executive function in the EOAD patients (r = -0.67, P < 0.05). Conclusion: In contrast to the LOAD patients, patients with EOAD exhibited more widely disrupted interhemispheric functional and structural connectivity, which overlapped well across brain regions. In addition, for the EOAD patients, decreased interhemispheric connectivity related to executive deficits. Our study suggested that different interhemispheric connectivity damage patterns may contribute to the distinct clinical profiles in EOAD and LOAD.

Giant cell tumor of the tendon sheath: Magnetic resonance imaging findings in 38 patients.

The present study aimed to investigate the value of magnetic resonance imaging (MRI) in the diagnosis of giant cell tumor of the tendon sheath (GCTTS), including localized (L-) and diffuse (D-) types. A total of 38 patients with GCTTS, including 31 with L-GCTTS and 7 with D-GCTTS, diagnosed by surgery and pathology, were retrospectively analyzed. All patients underwent MRI examination. Of the 31 patients with L-GCTTS, the tumors were located in the hand and wrist (18 patients), the ankle and foot (10 cases), the knee joint (2 cases) and the temporomandibular joint (1 case). All 31 lesions were either located in relation to a tendon or were partially/completely enveloping it and all were well marginated. With respect to the 7 D-GCTTS patients, the tumors were located in the ankle and foot (6 cases) or the hand and wrist (1 cases). All 7 lesions presented as an aggressive soft tissue mass infiltrating the tendon sheath and adipose tissue around the joint. The characteristic internal signal of GCTTS, including L-GCTTS and D-GCTTS, was demonstrated by MRI examination. MRI is currently the optimal modality for preoperative assessment of tumor size, extent and invasion of adjacent joint and tenosynovial space.

Dual-input two-compartment pharmacokinetic model of dynamic contrast-enhanced magnetic resonance imaging in hepatocellular carcinoma.

AIM: To investigate the feasibility of a dual-input two-compartment tracer kinetic model for evaluating tumorous microvascular properties in advanced hepatocellular carcinoma (HCC). METHODS: From January 2014 to April 2015, we prospectively measured and analyzed pharmacokinetic parameters [transfer constant (Ktrans), plasma flow (Fp), permeability surface area product (PS), efflux rate constant (kep), extravascular extracellular space volume ratio (ve), blood plasma volume ratio (vp), and hepatic perfusion index (HPI)] using dual-input two-compartment tracer kinetic models [a dual-input extended Tofts model and a dual-input 2-compartment exchange model (2CXM)] in 28 consecutive HCC patients. A well-known consensus that HCC is a hypervascular tumor supplied by the hepatic artery and the portal vein was used as a reference standard. A paired Student's t-test and a nonparametric paired Wilcoxon rank sum test were used to compare the equivalent pharmacokinetic parameters derived from the two models, and Pearson correlation analysis was also applied to observe the correlations among all equivalent parameters. The tumor size and pharmacokinetic parameters were tested by Pearson correlation analysis, while correlations among stage, tumor size and all pharmacokinetic parameters were assessed by Spearman correlation analysis. RESULTS: The Fp value was greater than the PS value (FP = 1.07 mL/mL per minute, PS = 0.19 mL/mL per minute) in the dual-input 2CXM; HPI was 0.66 and 0.63 in the dual-input extended Tofts model and the dual-input 2CXM, respectively. There were no significant differences in the kep, vp, or HPI between the dual-input extended Tofts model and the dual-input 2CXM (P = 0.524, 0.569, and 0.622, respectively). All equivalent pharmacokinetic parameters, except for ve, were correlated in the two dual-input two-compartment pharmacokinetic models; both Fp and PS in the dual-input 2CXM were correlated with Ktrans derived from the dual-input extended Tofts model (P = 0.002, r = 0.566; P = 0.002, r = 0.570); kep, vp, and HPI between the two kinetic models were positively correlated (P = 0.001, r = 0.594; P = 0.0001, r = 0.686; P = 0.04, r = 0.391, respectively). In the dual input extended Tofts model, ve was significantly less than that in the dual input 2CXM (P = 0.004), and no significant correlation was seen between the two tracer kinetic models (P = 0.156, r = 0.276). Neither tumor size nor tumor stage was significantly correlated with any of the pharmacokinetic parameters obtained from the two models (P > 0.05). CONCLUSION: A dual-input two-compartment pharmacokinetic model (a dual-input extended Tofts model and a dual-input 2CXM) can be used in assessing the microvascular physiopathological properties before the treatment of advanced HCC. The dual-input extended Tofts model may be more stable in measuring the ve; however, the dual-input 2CXM may be more detailed and accurate in measuring microvascular permeability.

A small interfering RNA targeting vascular endothelial growth factor efficiently inhibits growth of VX2 cells and VX2 tumor model of hepatocellular carcinoma in rabbit by transarterial embolization-mediated siRNA delivery.

INTRODUCTION: Hepatocellular carcinoma is currently the second leading cause of cancer-related deaths worldwide with an increasing incidence. OBJECTIVE: The objective of this study is to investigate the effect of vascular endothelial growth factor small interfering RNA (VEGF-siRNA) on rabbit VX2 carcinoma cell viability in vitro and the effect of transarterial embolization (TAE)-mediated VEGF-siRNA delivery on the growth of rabbit VX2 liver-transplanted model in vivo. METHODS: Quantitative reverse transcription polymerase chain reaction, enzyme-linked immunosorbent assay, and Western blot technologies were used to detect the expression level of VEGF. TAE and computed tomography scan were used to deliver the VEGF-siRNA and detect the tumor volume in vivo, respectively. Microvessel density was detected by immunohistochemistry with CD34 antibody. A biochemical autoanalyzer was used to evaluate the hepatic and renal toxicity. RESULTS: The designed VEGF-siRNAs could effectively decrease the expression levels of VEGF mRNA and protein in vitro and in vivo. In vitro, the viability of rabbit VX2 carcinoma cells was reduced by 38.5%±7.3% (VEGF-siRNA no 1) and 30.0%±5.8% (VEGF-siRNA no 3) at 48 hours after transfection. Moreover, in rabbit VX2 liver-transplanted model, the growth ratios of tumors at 28 days after TAE-mediated siRNA delivery were 155.18%±19.42% in the control group, 79.67%±19.63% in the low-dose group, and 36.09%±15.73% in the high-dose group, with significant differences among these three groups. Microvessel density dropped to 34.22±4.01 and 22.63±4.07 in the low-dose group and high-dose group, respectively, compared with the control group (57.88±5.67), with significant differences among these three groups. Furthermore, inoculation of VX2 tumor into the liver itself at later stage induced significant increase in alanine aminotransferase and aspartate aminotransferase, indicating an obvious damage of liver functions, while treatment of VX2 tumor via TAE-mediated VEGF-siRNA had no toxicity to the livers and kidneys of rabbits, and VEGF-siRNA had the ability to protect liver damage induced by tumor growth. CONCLUSION: This is the first study to demonstrate that targeting VEGF via TAE-mediated siRNA delivery may become a powerful new option for effective treatment of hepatocellular carcinoma in the clinic.

Radiological and clinical findings of osseous peripheral primitive neuroectodermal tumors.

Peripheral primitive neuroectodermal tumor (pPNET) is a rare and highly malignant undifferentiated type of tumor. The aim of the present study was to analyze the computed tomography (CT), magnetic resonance imaging (MRI) and clinical findings of osseous pPNET. The present study retrospectively analyzed the clinical data and CT findings from 15 patients with osseous pPNET; the MRI findings from 11 of these 15 patients were confirmed by histopathological examination. The 15 patients included 9 men and 6 women. The mean patient age was 29 years (range, 16-64 years) and 11 cases were aged <30 years. A CT scan was performed in 15 cases and the findings included a lytic lesion (13 cases), a lytic lesion with irregular sclerosis and dilation (2 cases), a soft tissue mass (15 cases), calcification (2 cases) and periosteal reaction (5 cases). A total of 9 cases of soft tissue mass were heterogeneous, with different sizes of lower-density necrotic areas. An enhanced MRI scan was performed in 11 cases. On T1-weighted images (WI), the soft tissue mass was isointense (8 cases) and marginally hyperintense (3 cases). On T2WI, aggressive soft tissue masses were heterogeneous iso- or hyperintense (11 cases). On contrast-enhanced T1WI, marked heterogeneous enhancement was present in 10 cases and intermediate heterogeneous enhancement in 1 case. The results indicated that osseous pPNET mainly affects male adolescents and young adults. The CT findings of osseous pPNET were destructive lesions with a soft tissue mass and, occasionally, with periosteal reaction. The tumor was often isodense, with patchy hypodense areas. Tumor calcification was uncommon. The MRI findings were those of an aggressive soft tissue mass exhibiting isointensity on T1WI and iso- or hyperintensity on T2WI, with marked heterogeneous enhancement. Although the imaging characteristics of pPNETs may be non-specific, CT and MRI may be useful in delineating the extent of the tumor, identifying distant metastases, predicting resectability and monitoring treatment.

[Cerebral lesions of DWI hyperintensity in patients with subacute stroke assessed by intravoxel incoherent motion technique].

OBJECTIVE: To investigate the cerebral lesions of diffusion weighted imaging (DWI) hyperintensity in patients with subacute stroke with intravoxel incoherent motion (IVIM) technique. METHODS: The clinical data of 20 patients with ischemic stroke (3 to 7 d after onset) who underwent DWI and IVIM scanning between June 2014 and July 2015, were retrospectively analyzed. The parameters from IVIM including slow diffusion coefficient (D), fast diffusion coefficient (D(*)) and perfusion fraction (f) were processed. DWI hyperintensity was segmented by its signal intensity greater than the mean+2 standard deviations of the value in the homologous contralateral region. Then, DWI hyperintensity was classified into two regions of interest (ROIs): infarction core and peri-core with the ADC threshold of 0.55 × 10⁻³ mm²/s. The mirrored ROIs of infarction core and peri-core were also obtained. Then, we measured the values of ADC and D, D(*) and f in these ROIs. The ratios of ADC (rADC), D (rD), D(*) (rD(*)) and f (rf) were also calculated (e.g., rADC=ADCinfarction core/ADCmirrored region). RESULTS: Compared with mirrored region, ADC, D and f in the infarction core region decreased by 45% (P<0.001), 42% (P<0.001) and 32% (P<0.001), respectively; while ADC, D and f in the peri-core region decreased by 22% (P<0.001), 32% (P<0.001) and 8% (P=0.009), respectively. The values of rADC, rD, rD(*) and rf in the infarction core region were significantly lower than those in the peri-core region (all P<0.001). Pearson analysis showed that rADC was positively correlated with rf in the peri-core region (r=0.467, P=0.038). CONCLUSION: During subacute stage of stroke, compared to the infarction core region within DWI hyperintensity, D and f increase in the peri-core region of DWI hyperintensity, reflecting the increased water diffusion in microstructure and perfusion volume in microvasculature. This result shows that the potential reason for the heterogeneous ADC signal is associated with the disappearance of cellular edema and microvascular compensatory with increased blood volume.

Rare presentation of peripheral primitive neuroectodermal tumor in the maxilla and mandible: A report of two cases.

Peripheral primitive neuroectodermal tumor (pPNET) is a rare and highly malignant undifferentiated tumor, which presents in infants and young adults. pPNETs in the head and neck region are uncommon and have a varying incidence of occurrence. Peripheral PNETs of the maxilla and mandible are particularly rare. At present, only 16 cases of pPNET of the maxilla and 13 cases of pPNET of the mandible have been reported. The present study describes a case of pPNET of the maxilla in a 16-year-old male and a case of pPNET of the mandible in another 16-year-old male. The present study reports the radiological findings and the clinical courses of the two patients.

Hepatic sinusoidal obstruction syndrome caused by herbal medicine: CT and MRI features.

OBJECTIVE: To describe the CT and MRI features of hepatic sinusoidal obstruction syndrome (HSOS) caused by herbal medicine Gynura segetum. MATERIALS AND METHODS: The CT and MRI features of 16 consecutive Gynura segetum induced HSOS cases (12 men, 4 women) were analyzed. Eight patients had CT; three patients had MRI, and the remaining five patients had both CT and MRI examinations. Based on their clinical presentations and outcomes, the patients were classified into three categories: mild, moderate, and severe. The severity of the disease was also evaluated radiologically based on the abnormal hepatic patchy enhancement in post-contrast CT or MRI images. RESULTS: Ascites, patchy liver enhancement, and main right hepatic vein narrowing or occlusion were present in all 16 cases. Hepatomegaly and gallbladder wall thickening were present in 14 cases (87.5%, 14/16). Periportal high intensity on T2-weighted images was present in 6 cases (75%, 6/8). Normal liver parenchymal enhancement surrounding the main hepatic vein forming a clover-like sign was observed in 4 cases (25%, 4/16). The extent of patchy liver enhancement was statistically associated with clinical severity classification (kappa = 0.565). CONCLUSION: Ascites, patchy liver enhancement, and the main hepatic veins narrowing were the most frequent signs of herbal medicine induced HSOS. The grade of abnormal patchy liver enhancement was associated with the clinical severity.

Changes in spontaneous brain activity in early Parkinson's disease.

Resting state brain activity can provide valuable insights into the pathophysiology of Parkinson's disease (PD). The purpose of the present study was (a) to investigate abnormal spontaneous neuronal activity in early PD patients using resting-state functional MRI (fMRI) with a regional homogeneity (ReHo) method and (b) to demonstrate the potential of using changes in abnormal spontaneous neuronal activity for monitoring the progression of PD during its early stages. Seventeen early PD patients were assessed with the Unified Parkinson's Disease Rating Scale (UPDRS), the Hoehn and Yahr disability scale and the Mini-mental State Examination (MMSE) were compared with seventeen gender- and age-matched healthy controls. All subjects underwent MRI scans using a 1.5T General Electric Signa Excite II scanner. The MRI scan protocol included whole-brain volumetric imaging using a 3D inversion recovery prepared (IR-Prep) fast spoiled gradient-echo pulse sequence and 2D multi-slice (22 axial slices covering the whole brain) resting-state fMRI using an echo planar imaging (EPI) sequence. Images were analyzed in SPM5 together with a ReHo algorithm using the in-house software program REST. A corrected threshold of p<0.05 was determined by AlphaSim and used in statistical analysis. Compared with the healthy controls, the early PD group showed significantly increased ReHo in a number of brain regions, including the left cerebellum, left parietal lobe, right middle temporal lobe, right sub-thalamic nucleus areas, right superior frontal gyrus, middle frontal gyrus (MFG), right inferior parietal lobe (IPL), right precuneus lobe, left MFG and left IPL. Additionally, significantly reduced ReHo was also observed in the early PD patients in the following brain regions: the left putamen, left inferior frontal gyrus, right hippocampus, right anterior cingulum, and bilateral lingual gyrus. Moreover, in PD patients, ReHo in the left putamen was negatively correlated with the UPDRS scores (r=-0.69). These results indicate that the abnormal resting state spontaneous brain activity associated with patients with early PD can be revealed by Reho analysis.