Enabling biomedical technologies for chronic myelogenous leukemia (CML) biomarkers detection.

Chronic myelogenous/myeloid leukemia (CML) is a type of cancer of bone marrow that arises from hematopoietic stem cells and affects millions of people worldwide. Eighty-five percent of the CML cases are diagnosed during chronic phase, most of which are detected through routine tests. Leukocytes, micro-Ribonucleic Acids, and myeloid markers are the primary biomarkers for CML diagnosis and are mainly detected using real-time reverse transcription polymerase chain reaction, flow cytometry, and genetic testing. Though multiple therapies have been developed to treat CML, early detection still plays a pivotal role in the overall patient survival rate. The current technologies used for CML diagnosis are costly and are confined to laboratory settings which impede their application in the point-of-care settings for early-stage detection of CML. This study provides detailed analysis and insights into the significance of CML, patient symptoms, biomarkers used for testing, and best possible detection techniques responsible for the enhancement in survival rates. A critical and detailed review is provided around potential microfluidic devices that can be adapted to detect the biomarkers associated with CML while enabling point-of-care testing for early diagnosis of CML to improve patient survival rates.

Exploring the anticancer properties of a new nicotinamide analogue: Investigations into in silico analysis, antiproliferative effects, selectivity, VEGFR-2 inhibition, apoptosis induction, and migration suppression.

BACKGROUND: This study focuses on the development and evaluation of (E)-N-(3-(1-(2-(4-bromobenzoyl)hydrazono)ethyl)phenyl)nicotinamide (BHEPN) as a potential inhibitor of Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2). METHODS: Computational investigations as density function theory (DFT), docking, molecular dynamics (MD) simulations, and ADMET) in addition to in vitro (VEGFR-2 inhibition, cytotoxicity against HepG2 and MCF-7 cancer cell lines, selectivity index, cells cycle analysis, apoptosis investigation, and cells migration assay) studies were conducted. RESULTS: DFT calculations determined the three-dimensional structure and indicated the reactivity of BHEPN. Molecular docking, and MD simulations analysis showed the BHEPN's binding affinity and its potential as a VEGFR-2 inhibitor. ADMET assessments predicted BHEPN's safety and drug-like characteristics. In vitro investigations confirmed the inhibition of VEGFR-2 with an IC50 value of 0.320 ± 0.012 µM. BHEPN also exhibited remarkable cytotoxic effects against HepG2 and MCF-7 cancer cell lines, with IC50 values of 0.19 ± 0.01 µM and 1.18 ± 0.01 µM, respectively, outperforming Sorafenib's IC50 values (2.24 ± 0.06 µM and 3.17 ± 0.01 µM), respectively. Notably, BHEPN displayed a higher IC50 value of 4.11 ± 0 µM against the non-carcinogenic Vero cell lines, indicating selectivity index values of 21.6 and 3.4 against the tested cancer cell lines, respectively. In a flow cytometry assay, BHEPN induced HepG2 cell cycle arrest at the G1/S phase. Moreover, BHEPN increased the incidence of early and late apoptosis in HepG2 cell lines (from 1.38% and 0.22%) in control cells to (4.11-26.02%) in the treated cells, respectively. Additionally, the percentage of necrosis raised to 13.39%, in contrast to 0.62% in control cells. Finally, BHEPN was able to reduce the migration and wound healing abilities in HepG2 cells to 38.89% compared to 87.92% in untreated cells after 48 h. These in vitro results aligned with the computational predictions, providing strong evidence of BHEPN's efficacy and safety in anticancer applications. CONCLUSIONS: BHEPN is a promising candidate for the development of novel anticancer agents through further in vitro and in vivo investigations.

AQAFI: a bioanalytical method for automated KPIs quantification of fluorescent images of human leukocytes and micro-nano particles.

Micro-nanoparticle and leukocyte imaging find significant applications in the areas of infectious disease diagnostics, cellular therapeutics, and biomanufacturing. Portable fluorescence microscopes have been developed for these measurements, however, quantitative assessment of the quality of images (micro-nanoparticles, and leukocytes) captured using these devices remains a challenge. Here, we present a novel method for automated quality assessment of fluorescent images (AQAFI) captured using smartphone fluorescence microscopes (SFM). AQAFI utilizes novel feature extraction methods to identify and measure multiple features of interest in leukocyte and micro-nanoparticle images. For validation of AQAFI, fluorescent particles of different diameters (8.3, 2, 1, 0.8 µm) were imaged using custom-designed SFM at a range of excitation voltages (3.8-4.5 V). Particle intensity, particle vicinity intensity, and image background noise were chosen as analytical parameters of interest and measured by the AQAFI algorithm. A control method was developed by manual calculation of these parameters using ImageJ which was subsequently used to validate the performance of the AQAFI method. For micro-nanoparticle images, correlation coefficients with R2 > 0.95 were obtained for each parameter of interest while comparing AQAFI vs. control (ImageJ). Subsequently, key performance indicators (KPIs) i.e., signal difference to noise ratio (SDNR) and contrast to noise ratio (CNR) were defined and calculated for these micro-nano particle images using both AQAFI and control methods. Finally, we tested the performance of the AQAFI method on the fluorescent images of human peripheral blood leukocytes captured using our custom SFM. Correlation coefficients of R2 = 0.99 were obtained for each parameter of interest (leukocyte intensity, vicinity intensity, background noise) calculated using AQAFI and control (ImageJ). A high correlation was also found between the CNR and SDNR values calculated using both methods. The developed AQAFI method thus presents an automated and precise way to quantify and assess the quality of fluorescent images (micro-nano particles and leukocytes) captured using portable SFMs. Similarly, this study finds broader applicability and can also be employed with benchtop microscopes for the quantitative assessment of their imaging performance.

A portable analog front-end system for label-free sensing of proteins using nanowell array impedance sensors.

Proteins are useful biomarkers for a wide range of applications such as cancer detection, discovery of vaccines, and determining exposure to viruses and pathogens. Here, we present a low-noise front-end analog circuit interface towards development of a portable readout system for the label-free sensing of proteins using Nanowell array impedance sensing with a form factor of approximately 35cm2. The electronic interface consists of a low-noise lock-in amplifier enabling reliable detection of changes in impedance as low as 0.1% and thus detection of proteins down to the picoMolar level. The sensitivity of our system is comparable to that of a commercial bench-top impedance spectroscope when using the same sensors. The aim of this work is to demonstrate the potential of using impedance sensing as a portable, low-cost, and reliable method of detecting proteins, thus inching us closer to a Point-of-Care (POC) personalized health monitoring system. We have demonstrated the utility of our system to detect antibodies at various concentrations and protein (45 pM IL-6) in PBS, however, our system has the capability to be used for assaying various biomarkers including proteins, cytokines, virus molecules and antibodies in a portable setting.

Excitation modalities for enhanced micro and nanoparticle imaging in a smartphone coupled 3D printed fluorescent microscope.

Smartphone fluorescent microscopes (SFM) offer many functional characteristics similar to their benchtop counterparts at a fraction of the cost and have been shown to work for biomarker detection in many biomedical applications. However, imaging and quantification of bioparticles in the sub-micron and nanometer range remains challenging as it requires aggressive robustness and high-performance metrics of the building blocks of SFM. Here, we explored multiple excitation modalities and their performance on the imaging capability of an SFM. Employing spatial positional variations of the excitation source with respect to the imaging sample plane (i.e., parallel, perpendicular, oblique), we developed three distinct SFM variants. These SFM variants were tested using green-fluorescent beads of four different sizes (8.3, 2, 1, 0.8 µm). Optimal excitation voltage range was determined by imaging these beads at multiple excitation voltages to optimize for no data loss and acceptable noise levels for each SFM variant. The SFM with parallel excitation was able to only image 8.3 µm beads while the SFM variants with perpendicular and oblique excitation were able to image all four bead sizes. Relative performance of the SFM variants was quantified by calculating signal difference to noise ratio (SDNR) and contrast to noise ratio (CNR) from the captured images. SFM with oblique excitation generated the highest SDNR and CNR values, whereas, for power consumption, SFM with perpendicular excitation generated the best results. This study sheds light on significant findings related to performance of SFM systems and their potential utility in biomedical applications involving sub-micron imaging. Similarly, findings of this study are translatable to benchtop microscopy instruments as well as to enhance their imaging performance metrics.

Disrupted Functional Connectivity Within and Between Resting-State Networks in the Subacute Stage of Post-stroke Aphasia.

Background: Post-stroke aphasia (PSA) results from brain network disorders caused by focal stroke lesions. However, it still remains largely unclear whether the impairment is present in intra- and internetwork functional connectivity (FC) within each resting-state network (RSN) and between RSNs in the subacute stage of PSA. Objectives: This study aimed to investigate the resting-state FC within and between RSNs in patients with PSA and observe the relationships between FC alterations and Western Aphasia Battery (WAB) measures. Methods: A total of 20 individuals with subacute PSA and 20 healthy controls (HCs) were recruited for functional MRI (fMRI) scanning, and only patients with PSA underwent WAB assessment. Independent component analysis was carried out to identify RSNs. Two-sample t-tests were used to calculate intra- and internetwork FC differences between patients with PSA and HCs. The results were corrected for multiple comparisons using the false discovery rate (FDR correction, p < 0.05). Partial correlation analysis was performed to observe the relationship between FC and WAB scores with age, gender, mean framewise displacement, and lesion volume as covariates (p < 0.05). Results: Compared to HCs, patients with PSA showed a significant increase in intranetwork FC in the salience network (SN). For internetwork FC analysis, patients showed a significantly increased coupling between left frontoparietal network (lFPN) and SN and decreased coupling between lFPN and right frontoparietal network (rFPN) as well as between lFPN and posterior default mode network (pDMN) (FDR correction, p < 0.05). Finally, a significant positive correlation was found between the intergroup difference of FC (lFPN-rFPN) and auditory-verbal comprehension (p < 0.05). Conclusion: Altered FC was revealed within and between multiple RSNs in patients with PSA at the subacute stage. Reduced FC between lFPN and rFPN was the key element participating in language destruction. These findings proved that PSA is a brain network disorder caused by focal lesions; besides, it may improve our understanding of the pathophysiological mechanisms of patients with PSA at the subacute stage.

Liquid Film Translocation Significantly Enhances Nasal Spray Delivery to Olfactory Region: A Numerical Simulation Study.

Previous in vivo and ex vivo studies have tested nasal sprays with varying head positions to enhance the olfactory delivery; however, such studies often suffered from a lack of quantitative dosimetry in the target region, which relied on the observer's subjective perception of color changes in the endoscopy images. The objective of this study is to test the feasibility of gravitationally driven droplet translocation numerically to enhance the nasal spray dosages in the olfactory region and quantify the intranasal dose distribution in the regions of interest. A computational nasal spray testing platform was developed that included a nasal spray releasing model, an airflow-droplet transport model, and an Eulerian wall film formation/translocation model. The effects of both device-related and administration-related variables on the initial olfactory deposition were studied, including droplet size, velocity, plume angle, spray release position, and orientation. The liquid film formation and translocation after nasal spray applications were simulated for both a standard and a newly proposed delivery system. Results show that the initial droplet deposition in the olfactory region is highly sensitive to the spray plume angle. For the given nasal cavity with a vertex-to-floor head position, a plume angle of 10° with a device orientation of 45° to the nostril delivered the optimal dose to the olfactory region. Liquid wall film translocation enhanced the olfactory dosage by ninefold, compared to the initial olfactory dose, for both the baseline and optimized delivery systems. The optimized delivery system delivered 6.2% of applied sprays to the olfactory region and significantly reduced drug losses in the vestibule. Rheological properties of spray formulations can be explored to harness further the benefits of liquid film translocation in targeted intranasal deliveries.

The feasibility of non-contrast-enhanced zero echo time magnetic resonance angiography for characterization of intracranial atherosclerotic disease.

BACKGROUND: Accurate and non-invasive assessment of intracranial atherosclerotic disease (ICAD) is important because of its effect on treatment planning. The aim of this study is to investigate if zero echo time (zTE) magnetic resonance angiography (zTE-MRA) is feasible in the characterization of ICAD. METHODS: A total of 175 patients with ICAD were recruited. ZTE-MRA and time-of-flight (TOF)-MRA sequences were conducted for all participants using a 3T clinical MR system. Forty-one patients also underwent digital subtraction angiography (DSA), and were confirmed to have intracranial arterial stenosis (ICAS). Weighted kappa (κ) statistics were used to assess the inter-observer agreement and diagnostic consistency of both zTE- and TOF-MRA, using DSA as a reference. The Wilcoxon signed-rank test was used to evaluate differences in image quality between zTE- and TOF-MRA images. The nonparametric test of multiple paired samples was used to compare the results of vascular stenosis diagnosis between zTE-, TOF-MRA and DSA. RESULTS: Supported by high inter-observer agreement (weighted κ=0.78), zTE-MRA generated significantly higher scores than TOF-MRA for susceptibility artifact signal (mean: 3.03±0.98 vs. 2.72±1.09; P=0.017) and flow signal in parent artery (mean: 3.63±0.49 vs. 3.07±0.82; P<0.001). Additionally, zTE-MRA showed more robust diagnostic performance than TOF-MRA for patients with ICAD and degree of vascular stenosis (P<0.05), and was highly consistent with reference DSA images (weighted κ=0.80). CONCLUSIONS: ZTE-MRA has potential for use as a routine clinical method for patients with ICAD.

A modular microscopic smartphone attachment for imaging and quantification of multiple fluorescent probes using machine learning.

Portable smartphone-based fluorescent microscopes are becoming popular owing to their ability to provide major functionalities offered by regular benchtop microscopes at a fraction of the cost. However, smartphone-based microscopes are still limited to a single fluorophore, fixed magnification, the inability to work with a different smartphones, and limited usability to either glass slides or cover slips. To overcome these challenges, here we present a modular smartphone-based microscopic attachment. The modular design allows the user to easily swap between different sets of filters and lenses, thereby enabling utility of multiple fluorophores and magnification levels. Our microscopic smartphone attachment can also be used with different smartphones and was tested with Nokia Lumia 1020, Samsung Galaxy S9+, and an iPhone XS. Further, we showed imaging results of samples on glass slides, cover slips, and microfluidic devices. A 1951 USAF resolution test target was used to quantify the maximum resolution of the microscope which was found to be 3.9 µm. The performance of the smartphone-based microscope was compared with a benchtop microscope and we found an R2 value of 0.99 using polystyrene beads and blood cells isolated from human blood samples collected from Robert Wood Johnson Medical Hospital. Additionally, to count the particles (cells and beads) imaged from the smartphone-based fluorescent microscope, we developed artificial neural networks (ANNs) using multiple training algorithms, and evaluated their performances compared to the control (ImageJ). Finally, we did ANOVA and Tukey's post-hoc analysis and found a p-value of 0.97 which shows that no statistical significant difference exists between the performance of the trained ANN and control (ImageJ).

Salvadora persica mediated synthesis of silver nanoparticles and their antimicrobial efficacy.

Silver nanoparticles (AgNPs) exhibit strong antimicrobial properties against many pathogens. Traditionally employed chemical methods for AgNPs synthesis are toxic for the environment. Here, we report a quicker, simpler, and environmentally benign process to synthesize AgNPs by using an aqueous 'root extract' of Salvadora persica (Sp) plant as a reducing agent. The synthesized Salvadora persica nano particles (SpNPs) showed significantly higher antimicrobial efficacy compared to earlier reported studies. We characterized SpNPs using UV-Vis spectroscopy, Fourier Transform Infrared Spectroscopy (FTIR), Transmission Electron Microscopy (TEM), Field Emission Scanning Electron Microscopy (FE-SEM), Dynamic Light Scattering (DLS) and X-ray powder diffraction (P-XRD). UV-Vis spectrum showed the highest absorbance at 420 nm. FTIR analysis depicts presence of bond stretching including OH- (3300 cm-1), C=N- (2100 cm-1) and NH- (1630 cm-1) which are attributed in the involvement of phenolics, proteins or nitrogenous compounds in reduction and stabilization of AgNPs. TEM, FE-SEM and DLS analysis revealed the spherical and rod nature of SpNPs and an average size of particles as 37.5 nm. XRD analysis showed the presence of the cubic structure of Ag which confirmed the synthesis of silver nanoparticles. To demonstrate antimicrobial efficacy, we evaluated SpNPs antimicrobial activity against two bacterial pathogens (Escherichia coli (ATCC 11229) and Staphylococcus epidermidis (ATCC 12228)). SpNPs showed a significantly high inhibition for both pathogens and minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were found to be 0.39 µg/mL and 0.78 µg/mL for E. coli while 0.19 µg/mL and 0.39 µg/mL for S. epidermidis respectively. Further, Syto 16 staining of bacterial cells provided a supplemental confirmation of the antimicrobial efficacy as the bacterial cells treated with SpNPs stop to fluoresce compared to the untreated bacterial cells. Our highly potent SpNPs will likely have a great potential for many antimicrobial applications including wound healing, water purification, air filtering and other biomedical applications.

Potential Microfluidic Devices for COVID-19 Antibody Detection at Point-of-Care (POC): A Review.

COVID-19 has been declared a global pandemic which has brought the world economy and the society to a standstill. The current emphasis of testing is on detection of genetic material of SARS-CoV-2. Such tests are useful for assessing the current state of a subject: Infected or not infected. In addition to such tests, antibody testing is necessary to stratify the population into three groups: never exposed, infected, and immune. Such a stratification is necessary for safely reopening the society and remobilizing the economy. The aim of this review article is to inform the audience of the current diagnostic and surveillance technologies that are being employed for the detection of SARS-CoV-2 antibodies along with their shortcomings, and to highlight microfluidic sensors and devices that show promise of being commercialized for detection and quantification of SARS-CoV-2 antibodies in low-resource and Point-of-Care (POC) settings.

Profiling single-cell level phagocytic activity distribution with blood lactate levels.

The ability to kill infecting microbes is an essential facet of our immune response to an infection. However, phagocytic ability is often overlooked as a part of immunological profile in infected patients' diagnosis, as the understanding of phagocytic capabilities in disease states is incomplete. In this work, we have evaluated for the first time the relationship between blood lactate level and the neutrophil phagocytic activity at a single-cell level. Blood samples (N = 19) were grouped on the basis of their blood lactate levels i.e., below (control) or above 2 mmol L-1 (high-risk) (i.e., 2 mmol L-1 is a common clinical lactate threshold used for patients' triage). Neutrophils were isolated from whole blood and then incubated with fluorescent IgG coated beads for 40 minutes, and the ability of each neutrophil to internalize beads was quantified. Single-cell phagocytic activity analysis has shown interesting findings such as: (i) a single neutrophil was able to internalize up to 7 beads, (ii) for a control group, 39.76% cells didn't internalize any beads, while for a high-risk group, 30.65% cells didn't show any phagocytic activity, (iii) similarly, 30.46% cells internalize only 1 bead in a control group, while for a high-risk group the activity is slightly higher with only 31.73% cells showing single bead internalization, and (iv) 7 bead internalization activity was much higher for samples in a high-risk group (0.6% cells) compared to a control group (0.17% cells). We used multiple statistical tests to compare these differences. For a two-tailed T-test, we used the mean phagocytic activity of the cells (i.e., the average number of beads internalized by cells) isolated from the blood samples in the two groups (1.14 vs. 1.35) and found the p-value to be 0.08. We also used principal component analysis (PCA) on this high dimensional phagocytic activity distribution data and performed dimension reduction. However, the first 3 principal components didn't show a clear distinction between groups. Next, we developed machine learning models using artificial neural networks (ANNs) to differentiate between the distribution of phagocytic activity in neutrophil populations of the two groups. Our models yielded area under curve (AUC) values below 0.7 for receiver operator characteristic curves. Although our study highlighted interesting phagocytic activity findings at a single cell level, it further highlights the need for integration of an individual patient's medical record to get more personalized insights into individual phagocytic activity in the future.

Potential effect of bio-surfactants on sea spray generation in tropical cyclone conditions.

Despite significant improvement in computational and observational capabilities, predicting intensity and intensification of major tropical cyclones remains a challenge. In 2017 Hurricane Maria intensified to a Category 5 storm within 24 h, devastating Puerto Rico. In 2019 Hurricane Dorian, predicted to remain tropical storm, unexpectedly intensified into a Category 5 storm and destroyed the Bahamas. The official forecast and computer models were unable to predict rapid intensification of these storms. One possible reason for this is that key physics, including microscale processes at the air-sea interface, are poorly understood and parameterized in existing forecast models. Here we show that surfactants significantly affect the generation of sea spray, which provides some of the fuel for tropical cyclones and their intensification, but also provides some of the drag that limits intensity and intensification. Using a numerical model verified with a laboratory experiment, which predicts spray radii distribution starting from a 100 µm radius, we show that surfactants increase spray generation by 20-34%. We anticipate that bio-surfactants affect heat, energy, and momentum exchange through altered size distribution and concentration of sea spray, with consequences for tropical cyclone intensification or decline, particularly in areas of algal blooms and near coral reefs, as well as in areas affected by oil spills and dispersants.

Disrupted Resting-state Functional Connectivity of the Nucleus Basalis of Meynert in Parkinson's Disease with Mild Cognitive Impairment.

The basal nucleus of Meynert (BNM) shows structural abnormalities in Parkinson's disease with mild cognitive impairment (PD-MCI). However, it is yet unknown whether functional connectivity (FC) in the BNM (BNM-FC) is altered in patients with PD-MCI. Therefore, in this study, we compared the BNM-FC of patients with PD-MCI and PD patients with normal cognition (PD-NC), to evaluate the relationship between the observed differences of BNM-FC and neuropsychological test scores. Three patient groups, namely PD-MCI, PD-NC, and healthy controls (HCs) (n = 22 each) including were recruited for functional magnetic resonance imaging (fMRI) scanning and neuropsychological assessment. Analysis of covariance was used to assess the inter-group differences. The relationships between BNM-FC and results of cognitive tests were evaluated by partial correlation analysis. Multivariate pattern analysis was used to test whether PD-MCI can be distinguished from PD-NC based on the BNM-FC. Classifier performance was assessed through permutation testing. Compared to PD-NC and HCs, PD-MCI showed reduced BNM-FC in the right superior parietal lobe (SPL) and the right postcentral gyrus. Furthermore, a positive correlation was observed between BNM-FC and the clock copying test (CLOX)/auditory verbal learning test (AVLT) immediate recall scores. We found that 86.36% subjects were correctly classified based on the BNM-FC using the leave-one-out cross-validation (LOOCV) method, with a sensitivity of 90.91% and specificity of 81.82%. Our study provides new insights into the neural basis of cognitive dysfunction in PD patients. We also found that BNM-FC can be an effective feature to distinguish PD-MCI from PD-NC.

Dynamic Alterations of Spontaneous Neural Activity in Parkinson's Disease: A Resting-State fMRI Study.

Objective: To investigate the dynamic amplitude of low-frequency fluctuations (dALFFs) in patients with Parkinson's disease (PD) and healthy controls (HCs) and further explore whether dALFF can be used to test the feasibility of differentiating PD from HCs. Methods: Twenty-eight patients with PD and 28 demographically matched HCs underwent resting-state functional magnetic resonance imaging (rs-fMRI) scans and neuropsychological tests. A dynamic method was used to calculate the dALFFs of rs-fMRI data obtained from all subjects. The dALFF alterations were compared between the PD and HC groups, and the correlations between dALFF variability and disease duration/neuropsychological tests were further calculated. Then, the statistical differences in dALFF between both groups were selected as classification features to help distinguish patients with PD from HCs through a linear support vector machine (SVM) classifier. The classifier performance was assessed using a permutation test (repeated 5,000 times). Results: Significantly increased dALFF was detected in the left precuneus in patients with PD compared to HCs, and dALFF variability in this region was positively correlated with disease duration. Our results show that 80.36% (p < 0.001) subjects were correctly classified based on the SVM classifier by using the leave-one-out cross-validation method. Conclusion: Patients with PD exhibited abnormal dynamic brain activity in the left precuneus, and the dALFF variability could distinguish PD from HCs with high accuracy. Our results showed novel insights into the pathophysiological mechanisms of PD.

Segmental Liver Stiffness Evaluated with Magnetic Resonance Elastography Is Responsive to Endovascular Intervention in Patients with Budd-Chiari Syndrome.

OBJECTIVE: To assess segmental liver stiffness (LS) with MRI before and after endovascular intervention in patients with Budd-Chiari syndrome (BCS). MATERIALS AND METHODS: Twenty-three patients (13 males and 10 females; mean age, 42.6 ± 12.6 years; age range, 31-56 years) with BCS as a primary liver disease were recruited for this study. Two consecutive magnetic resonance elastography (MRE) examinations were performed before the endovascular treatment. Fifteen patients who underwent endovascular intervention treatment also had follow-up MRE scans within three days after the procedure. LS was measured in three liver segments: the right posterior, right anterior, and left medial segments. Inter-reader and inter-exam repeatability were analyzed with intraclass correlation coefficients (ICCs) and Bland-Altman analysis. Segmental LS and clinical characteristics before and after the intervention were also compared. RESULTS: Within three days of the endovascular intervention, all three segmental LS values decreased: LS of the right posterior segment = 7.23 ± 0.88 kPa (before) vs. 4.94 ± 0.84 kPa (after), LS of the right anterior segment = 7.30 ± 1.06 kPa (before) vs. 4.77 ± 0.85 kPa (after), and LS of the left medial segment = 7.22 ± 0.87 kPa (before) vs. 4.87 ± 0.72 kPa (after) (all p = 0.001). There was a significant correlation between LS changes and venous pressure gradient changes before and after treatments (r = 0.651, p = 0.009). The clinical manifestations of all 15 patients significantly improved after therapy. The MRE repeatability was excellent, with insignificant variations (inter-reader, ICC = 0.839-0.943: inter-examination, ICC = 0.765-0.869). Bland-Altman analysis confirmed excellent agreement (limits of agreement, 13.4-19.4%). CONCLUSION: Segmental LS measured by MRE is a promising repeatable quantitative biomarker for monitoring the treatment response to minimally invasive endovascular intervention in patients with BCS.

Diagnostic accuracy of magnetic resonance angiography for Budd-Chiari syndrome: A meta-analysis.

In recent years, the role of magnetic resonance angiography (MRA) in the diagnosis of Budd-Chiari Syndrome (BCS) has been the focus of various clinical studies. The purpose of the present study was to perform a meta-analysis of the diagnostic performance of MRA in patients with BCS by using digital subtraction angiography as a reference method. The search strategy for relevant research articles was based on the Cochrane Handbook for Systematic Reviews, and literature databases (including PubMed, Medline and China National Knowledge Infrastructure) and reference lists of retrieved studies published from 2000 to 2016 were searched. The Quality Assessment of Diagnostic Accuracy Studies tool was used to assess the methodological quality of these research studies by two reviewers independently. Summary estimates of the sensitivity, specificity, positive/negative likelihood ratio (LR+/-), diagnostic odds ratio (DOR) and the summary receiver operating characteristic (SROC) curve of MRA in identifying BCS were obtained. The pooled MRA estimates had a sensitivity of 97.6% [95% confidence interval (CI), 95.1-99.0%], a specificity of 70.7% (95% CI, 54.5-83.9%), an LR+ of 3.163 (95% CI, 2.03-4.94) and an LR- of 0.045 (95% CI, 0.02-0.09). The overall DOR was 94.053 (95% CI, 32.71-270.41). The area under the SROC curve was 0.972. In conclusion, MRA is an accurate modality for evaluating BCS.

Disrupted metabolic and functional connectivity patterns of the posterior cingulate cortex in cirrhotic patients: a study combining magnetic resonance spectroscopy and resting-state functional magnetic resonance imaging.

The association between metabolic activity and functional coupling of the posterior cingulate cortex (PCC) in cirrhotic patients remains undefined. Therefore, this study aimed to assess the association of functional coupling with metabolic patterns of PCC in resting cirrhotic patients. Twenty-six cirrhotic patients, including 10 with hepatic encephalopathy (HE) and 16 without HE, were assessed, alongside 21 control participants. Single-voxel proton magnetic resonance spectroscopy (MRS) of the PCC and resting-state functional MRI (rs-fMRI) were performed on a 3.0-T MR scanner. The ratios of all metabolites to creatine (Cr) and rs-fMRI parameters [including amplitude of low-frequency fluctuation (ALFF), node degree (Ki), and betweenness centrality (Bi)] were evaluated by analysis of variance. Associations of metabolite ratios with rs-fMRI parameters and venous ammonia were determined by Pearson's correlation analysis. Lower chlorine (Cho)/Cr (0.6±0.2 vs. 0.9±0.1, P<0.001) and higher ALFF (1.3±0.5 vs. 1.1±0.3, P=0.01) were found in cirrhotic patients in comparison with controls. In cirrhotic patients, the ALFF values correlated negatively with Cho/Cr (r=-0.397, P=0.044). Meanwhile, Bi values showed positive associations with glutamine+glutamate/Cr (r=0.500, P=0.009) and N-acetyl aspartate/Cr (r=0.581, P=0.006). In the HE subgroup, Ki correlated positively with Cho/Cr (r=0.867, P=0.001). In cirrhotic patients without HE, Bi values showed a high positive correlation with glutamate+glutamine/Cr (r=0.690, P=0.013). These findings suggest a close association between metabolic activity and functional coupling of the PCC in cirrhotic patients, especially those with HE, whose node degree of the PCC shows an overt positive correlation with Cho/Cr.

Texture analysis of diffusion weighted imaging for the evaluation of glioma heterogeneity based on different regions of interest.

The present study aimed to explore the role of texture analysis with apparent diffusion coefficient (ADC) maps based on different regions of interest (ROI) in determining glioma grade. Thirty patients with glioma underwent diffusion-weighted imaging (DWI). ADC values were determined from the following three ROIs: i) whole tumor; ii) solid portion; and iii) peritumoral edema. Texture features were compared between high-grade gliomas (HGGs) and low-grade gliomas (LGGs) using the non-parametric Wilcoxon rank-sum test or the unpaired Student's t-test. Receiver operating characteristic (ROC) curves were constructed to determine the optimum threshold for inhomogeneity values in discrimination of HGGs from LGGs. With a spearman rank correlation model, the aforementioned ADC inhomogeneity values were correlated with the Ki-67 labeling index. With whole tumor ROI, inhomogeneity values proved to be significantly different between HGGs and LGGs (P<0.001). With solid portion ROI, inhomogeneity and median values showed significant difference between HGGs and LGGs (P=0.001 and P=0.043, respectively). With peritumoral edema ROI, entropy and edema volume demonstrated positive results (P=0.016, P<0.001). The whole tumor inhomogeneity parameter performed with better diagnostic accuracy (P=0.048) than selecting the solid portion ROI. The association between inhomogeneity and Ki-67 labeling index was significantly positive in whole tumor and solid portion ROI (R=0.628, P<0.001 and R=0.470, P=0.009). Texture analysis of DWI based on different ROI can provide various significant parameters to evaluate tumor heterogeneity, which were correlated with tumor grade. Particularly, the inhomogeneity value derived from whole tumor ROI provided high diagnostic value and predicting the status of tumor proliferation.