Reproducibility for carotid wall segmentation using T1-weighted DANTE-SPACE sequence on high-resolution 3-T carotid MRI.

BACKGROUND: T1-weighted (T1W) magnetic resonance imaging (MRI) using the delay alternating with nutation for excitation-sampling perfection with application-optimized contrasts using different flip angle evolution (DANTE-SPACE) is the preferred imaging technique for evaluation of the vessel wall. PURPOSE: To evaluate the intra- and inter-rater reproducibility of carotid wall segmentation on T1W DANTE-SPACE in patients with symptomatic (acute stroke or transient ischemic attack) internal carotid artery (ICA) stenosis. MATERIAL AND METHODS: This prospective study included 25 patients with acute (≤3 months) stroke or transient ischemic attack and 50%-99% stenosis of the ICA. All patients underwent 3.0-T high-resolution carotid MRI. Two radiologists independently performed the manual segmentation of the vessel wall and inner lumen of the bilateral carotid artery on DANTE-SPACE. The intraclass correlation coefficient (ICC), Dice similarity coefficient (DSC), and Hausdorff distance (HD) were calculated. RESULTS: The ICCs for intra-rater reproducibility of carotid wall volume, inner lumen volume, and normalized wall index were 0.965, 0.990, and 0.962, respectively. The ICCs for inter-rater reproducibility of carotid wall volume, inner lumen, and normalized wall index were 0.856, 0.981, and 0.904. DSC and HD for intra- and inter-rater reproducibility of carotid wall segmentation were as follows: 0.873 and 0.809 (DSC); and 0.079 and 0.118 (HD), respectively. For evaluation of reproducibility only in the carotid artery with symptomatic stenosis, the ICCs for intra- and inter-rater reproducibility indicated all perfect agreement. CONCLUSION: T1W DANTE-SPACE is a reproducible sequence for evaluation of the carotid wall using carotid MRI in patients with symptomatic ICA stenosis.

Total intracranial hemorrhage volume measurement summating all compartments best in traumatic and nontraumatic intracranial bleeding.

BACKGROUND AND PURPOSE: The ANNEXA-4 trial measured hemostatic efficacy of andexanet alfa in patients with major bleeding taking factor Xa inhibitors. A proportion of this was traumatic and nontraumatic intracranial bleeding. Different measurements were applied in the trial including volumetrics to assess for intracranial bleeding depending on the compartment involved. We aimed to determine the most reliable way to measure intracranial hemorrhage (ICrH) volume by comparing individual brain compartment and total ICrH volume. METHODS: Thirty patients were randomly selected from the ANNEXA-4 database to assess measurement of ICrH volume by compartment and in total. Total and compartmental hemorrhage volumes were measured by five readers using Quantomo software. Each reader measured baseline hemorrhage volumes twice separated by 1 week. Twenty-eight different ANNEXA-4 subjects were also randomly selected to assess intra-rater reliability of total ICrH volume measurement change at baseline and 12-h follow up, performed by three readers twice to assess hemostatic efficacy categories used in ANNEXA-4. RESULTS: Compartmental minimal detectable change percentages (MDC%) ranged between 9.72 and 224.13, with the greatest measurement error occurring in patients with a subdural hemorrhage. Total ICrH volume measurements had the lowest MDC%, which ranged between 6.57 and 33.52 depending on the reader. CONCLUSION: Measurement of total ICrH volumes is more accurate than volume by compartment with less measurement error. Determination of hemostatic efficacy was consistent across readers, and within the same reader, as well as when compared to consensus read. Volumetric analysis of intracranial hemostatic efficacy is feasible and reliable when using total ICrH volumes.

Asymptomatic Common Carotid Artery Occlusion and Occipital-Vertebral Artery Anastomosis: A Case Report and Literature Review.

Common carotid artery occlusion (CCAO) is a very rare disorder that has rarely been studied. CCAO causes several neurological symptoms but can sometimes be asymptomatic due to the development of various anastomoses. Herein, we report the case of a 70-year-old male patient diagnosed with asymptomatic CCAO due to anastomotic flow. The patient underwent transfemoral cerebral angiography (TFCA) and was found to have CCAO with two collateral pathways, including an occipital artery-vertebral artery anastomosis. We emphasize the importance of TFCA when CCAO is suspected and review the types and anastomotic pathways of CCAO.

The Effect of Porosity on the Thermal Conductivity of Highly Thermally Conductive Adhesives for Advanced Semiconductor Packages.

This study suggests promising candidates as highly thermally conductive adhesives for advanced semiconductor packaging processes such as flip chip ball grid array (fcBGA), flip chip chip scale package (fcCSP), and package on package (PoP). To achieve an extremely high thermal conductivity (TC) of thermally conductive adhesives of around 10 Wm-1K-1, several technical methods have been tried. However, there are few ways to achieve such a high TC value except by using spherical aluminum nitride (AlN) and 99.99% purified aluminum oxide (Al2O3) fillers. Herein, by adapting highly sophisticated blending and dispersion techniques with spherical AlN fillers, the highest TC of 9.83 Wm-1K-1 was achieved. However, there were big differences between theoretically calculated TCs that were based on the conventional Bruggeman asymmetric model and experimentally measured TCs due to the presence of voids or pores in the composites. To narrow the gaps between these two TC values, this study also suggests a new experimental model that contains the porosity effect on the effective TC of composites in high filler loading ranges over 80 vol%, which modifies the conventional Bruggeman asymmetric model.

Highly-packed self-assembled graphene oxide film-integrated resistive random-access memory on a silicon substrate for neuromorphic application.

Resistive random-access memories (RRAMs) based on metal-oxide thin films have been studied extensively for application as synaptic devices in neuromorphic systems. The use of graphene oxide (GO) as a switching layer offers an exciting alternative to other materials such as metal-oxides. We present a newly developed RRAM device fabricated by implementing highly-packed GO layers on a highly doped Si wafer to yield a gradual modulation of the memory as a function of the number of input pulses. By using flow-enabled self-assembly, highly uniform GO thin films can be formed on flat Si wafers in a rapid and simple process. The switching mechanism was explored through proposed scenarios reconstructing the density change of the sp2cluster in the GO layer, resulting in a gradual conductance modulation. We analyzed that the current in a low resistance state could flow by tunneling or hopping via clusters because the distance between the sp2clusters in closely-packed GO layers is short. Finally, through a pattern-recognition simulation with a Modified National Institute of Standards and Technology database, the feasibility of using close-packed GO layers as synapse devices was successfully demonstrated.

Myelin Water Imaging of Nerve Recovery in Rehabilitating Stroke Patients.

BACKGROUND: Myelin water imaging (MWI) using MRI has been introduced as a method to quantify the integrity of myelin in vivo. However, the investigation of its potential to probe myelin changes has been limited. PURPOSE: To determine the myelin change using MWI in the corticospinal tract (CST) during the rehabilitation of stroke patients. STUDY TYPE: Longitudinal. POPULATION: A total of 24 stroke patients within 6 months from the onset (64.3 ± 16.1 years, 14 women, 10 men) and 10 healthy volunteers (27.0 ± 2.2 years, 2 women, 8 men). FIELD STRENGTH/SEQUENCE: Three-dimensional multiecho gradient echo sequence and diffusion-weighted echoplanar imaging sequence at 3 T. ASSESSMENT: The changes of myelin water fraction (MWF) and fractional anisotropy (FA) during rehabilitation were analyzed in the CST and other regions using tractography software and region of interest drawings by the radiologist. STATISTICAL TESTS: A paired t-test was performed to investigate the change of MRI metrics during rehabilitation. In addition, an independent two-sample t-test was performed to investigate the effects of different rehabilitation protocols. A P-value <0.05 was considered significant. RESULTS: In the CST, MWF significantly changed from 5.83 ± 0.91% to 6.23 ± 0.97% after rehabilitation while changes of FA (0.442 ± 0.038 to 0.443 ± 0.035) were not significant (P = 0.656). The rate of change in MWF and FA, which were 6.69% and 0.439% respectively, were significantly different. Other regions did not show significant changes (range of MWF change: -3.44% to -1.61%, range of FA change: -1.39% to 0.79%, and range of P-value: 0.144-0.761). Further analysis showed that those with additional robot-assisted rehabilitation had a significantly larger MWF change than those with conventional rehabilitation only (rate of change: 11.2% vs. 3.2%). DATA CONCLUSION: The feasibility of using MWI to monitor myelin content was demonstrated by showing the MWF changes during rehabilitation. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2.

High-Resolution Intracranial Vessel Wall MRI Findings Among Different Middle Cerebral Artery Territory Infarction Types.

OBJECTIVE: Intracranial atherosclerotic stroke occurs through various mechanisms, mainly by artery-to-artery embolism (AA) or branch occlusive disease (BOD). This study evaluated the spatial relationship between middle cerebral artery (MCA) plaques and perforating arteries among different MCA territory infarction types using vessel wall magnetic resonance imaging (VW-MRI). MATERIALS AND METHODS: We retrospectively enrolled patients with acute MCA infarction who underwent VW-MRI. Thirty-four patients were divided into three groups according to infarction pattern: 1) BOD, 2) both BOD and AA (BOD-AA), and 3) AA. To determine the factors related to BOD, the BOD and BOD-AA groups were combined into one group (with striatocapsular infarction [BOD+]) and compared with the AA group. To determine the factors related to AA, the BOD-AA and AA groups were combined into another group (with cortical infarction [AA+]) and compared with the BOD group. Plaque morphology and the spatial relationship between the perforating artery orifice and plaque were evaluated both quantitatively and qualitatively. RESULTS: The plaque margin in the BOD+ group was closer to the perforating artery orifice than that in the AA group (p = 0.011), with less enhancing plaque (p = 0.030). In the BOD group, plaques were mainly located on the dorsal (41.2%) and superior (41.2%) sides where the perforating arteries mainly arose. No patient in the AA group had overlapping plaques with perforating arteries at the cross-section where the perforator arose. Perforating arteries associated with culprit plaques were most frequently located in the middle two-thirds of the M1 segment (41.4%). The AA+ group had more stenosis (%) than the BOD group (39.73 ± 24.52 vs. 14.42 ± 20.96; p = 0.003). CONCLUSION: The spatial relationship between the perforating artery orifice and plaque varied among different types of MCA territory infarctions. In patients with BOD, the plaque margin was closer and blocked the perforating artery orifice, and stenosis degree and enhancement were less than those in patients with AA.

Effective End-to-End Deep Learning Process in Medical Imaging Using Independent Task Learning: Application for Diagnosis of Maxillary Sinusitis.

PURPOSE: This study aimed to propose an effective end-to-end process in medical imaging using an independent task learning (ITL) algorithm and to evaluate its performance in maxillary sinusitis applications. MATERIALS AND METHODS: For the internal dataset, 2122 Waters' view X-ray images, which included 1376 normal and 746 sinusitis images, were divided into training (n=1824) and test (n=298) datasets. For external validation, 700 images, including 379 normal and 321 sinusitis images, from three different institutions were evaluated. To develop the automatic diagnosis system algorithm, four processing steps were performed: 1) preprocessing for ITL, 2) facial patch detection, 3) maxillary sinusitis detection, and 4) a localization report with the sinusitis detector. RESULTS: The accuracy of facial patch detection, which was the first step in the end-to-end algorithm, was 100%, 100%, 99.5%, and 97.5% for the internal set and external validation sets #1, #2, and #3, respectively. The accuracy and area under the receiver operating characteristic curve (AUC) of maxillary sinusitis detection were 88.93% (0.89), 91.67% (0.90), 90.45% (0.86), and 85.13% (0.85) for the internal set and external validation sets #1, #2, and #3, respectively. The accuracy and AUC of the fully automatic sinusitis diagnosis system, including site localization, were 79.87% (0.80), 84.67% (0.82), 83.92% (0.82), and 73.85% (0.74) for the internal set and external validation sets #1, #2, and #3, respectively. CONCLUSION: ITL application for maxillary sinusitis showed reasonable performance in internal and external validation tests, compared with applications used in previous studies.

The Effect of Three Surgical Therapies to Increase Keratinized Mucosa Surrounding Dental Implants with Peri-Implantitis: A Pilot Study.

Background and Objectives: The purpose of this pilot study was to evaluate the clinical outcomes of three different methods for increasing the keratinized mucosa (KM) surrounding dental implants with peri-implantitis. Materials and methods: Twenty implant sites with peri-implantitis were divided into: (1) porcine collagen matrix (CM) group: seven implant sites; (2) apically positioned flap (APF) group: eight implant sites; and (3) free gingival graft (FGG) group: five implant sites. The KM width and clinical parameters (probing pocket depth (PPD) and bleeding on probing (BOP)) were measured at time points: before surgery (T0) and 30 (T1), 60 (T2), 90 (T3), and 180 (T4) days after surgery. Results: Regarding KM width, all the groups had significant differences for increasing horizontal and vertical KM width. The CM and FGG groups had greater KM than the APF group. There was a decrease in PPD in all three groups. APF and FGG showed significant differences in PPD at T1 and T2 compared to T0. Only the FGG group showed a significant difference in PPD at T3 and T4 compared with that at T0. BOP values were also reduced in all the groups at T1-T4 compared to T0. The APF and FGG groups showed a significant decrease in BOP. Conclusions: Three surgical therapies presented favorable results for increasing the KM surrounding implants. Compared with the FGG group, the CM showed similar results in increasing the KM around the dental implants with peri-implantitis.

A Deep Learning Model with High Standalone Performance for Diagnosis of Unruptured Intracranial Aneurysm.

PURPOSE: This study aimed to investigate whether a deep learning model for automated detection of unruptured intracranial aneurysms on time-of-flight (TOF) magnetic resonance angiography (MRA) can achieve a target diagnostic performance comparable to that of human radiologists for approval from the Korean Ministry of Food and Drug Safety as an artificial intelligence-applied software. MATERIALS AND METHODS: In this single-center, retrospective, confirmatory clinical trial, the diagnostic performance of the model was evaluated in a predetermined test set. After sample size estimation, the test set consisted of 135 aneurysm-containing examinations with 168 intracranial aneurysms and 197 aneurysm-free examinations. The target sensitivity and specificity were set as 87% and 92%, respectively. The patient-wise sensitivity and specificity of the model were analyzed. Moreover, the lesion-wise sensitivity and false-positive detection rate per case were also investigated. RESULTS: The sensitivity and specificity of the model were 91.11% [95% confidence interval (CI): 84.99, 95.32] and 93.91% (95% CI: 89.60, 96.81), respectively, which met the target performance values. The lesion-wise sensitivity was 92.26%. The overall false-positive detection rate per case was 0.123. Of the 168 aneurysms, 13 aneurysms from 12 examinations were missed by the model. CONCLUSION: The present deep learning model for automated detection of unruptured intracranial aneurysms on TOF MRA achieved the target diagnostic performance comparable to that of human radiologists. With high standalone performance, this model may be useful for accurate and efficient diagnosis of intracranial aneurysm.

Evaluating Change of Marginal Bone Height with Cone-Beam Computed Tomography Following Surgical Treatment with Guided Tissue Regeneration (Bone Grafting) or Access Flap Alone: A Retrospective Study.

Background and Objectives: This study aimed to evaluate the change of bone height following treatment of human intrabony defects with guided tissue regeneration (GTR) with bone grafting or access flap alone by cone-beam computed tomography (CBCT) scan. Materials and methods: This study was conducted as a retrospective longitudinal study. In this study, a total of 2281 teeth sites were included: the GTR group had 1210 sites, and the Flap group had 1071 sites. In the GTR group, demineralized freeze-dried bone (DFDBA) particles in combination with resorbable collagen membrane were used. No regenerative material was applied to the Flap group. CBCT images were taken twice at baseline and at least 2.5 months postoperatively. Bone heights were measured using software on CBCT images. Results: The bony change between the GTR and Flap groups was significantly different (p = 0.00001). Both males and females in the GTR group had smaller bone loss than in the Flap group. In age groups, significant differences of bony height between the GTR and Flap groups were observed in the subgroups consisting of those 29-45 and 46-53 years old. The non-smoking subjects in the GTR group had higher bone heights than those in the Flap group. In the absence of systemic disease and medicine, bone formation was higher in the GTR group than in the Flap group. In terms of oral position, the #14-17, #34-37, and #44-47 subgroups of the GTR group showed higher levels of bone heights than those of the Flap group. Conclusions. The results of this study indicated that the GTR procedure offers the additional benefit of higher bone heights than the Flap procedure does.

Transparent Electromagnetic Shielding Film Utilizing Imprinting-Based Micro Patterning Technology.

Utilization of methods involving component integration has accelerated, owing to the growth of the smart mobile industry. However, this integration leads to interference issues between the components, thereby elucidating the importance of the electromagnetic interference (EMI) shielding technology to solve such issues. EMI shielding technology has been previously implemented via the reflection or absorption of electromagnetic waves by using conductive materials. Nevertheless, to tackle the recent changes in the industry, a transparent and flexible EMI shielding technology is necessitated. In this study, a transparent and flexible EMI shielding material was fabricated by filling a conductive binder in a film comprising an intaglio pattern; this was achieved by using the ultraviolet (UV) imprinting technology to realize mass production. Subsequently, changes in the aperture ratio and shielding characteristics were analyzed according to the structure of the pattern. Based on this analysis, a square pattern was designed and a film with an intaglio pattern was developed through a UV imprinting process. Furthermore, it was confirmed that the transmittance, conductivity, and EMI shielding rate of the film were altered while changing the coating thickness of the conductive particles in the intaglio pattern. The final film prepared in this study exhibited characteristics that satisfied the required EMI shielding performance for electric and electronic applications, while achieving flexible structural stability and transparency.

Semi-automatic measurement of intracranial hemorrhage growth on non-contrast CT.

BACKGROUND: Manual segmentations of intracranial hemorrhage on non-contrast CT images are the gold-standard in measuring hematoma growth but are prone to rater variability. AIMS: We demonstrate that a convex optimization-based interactive segmentation approach can accurately and reliably measure intracranial hemorrhage growth. METHODS: Baseline and 16-h follow-up head non-contrast CT images of 46 subjects presenting with intracranial hemorrhage were selected randomly from the ANNEXA-4 trial imaging database. Three users semi-automatically segmented intracranial hemorrhage to measure hematoma volume for each timepoint using our proposed method. Segmentation accuracy was quantitatively evaluated compared to manual segmentations by using Dice similarity coefficient, Pearson correlation, and Bland-Altman analysis. Intra- and inter-rater reliability of the Dice similarity coefficient and intracranial hemorrhage volumes and volume change were assessed by the intraclass correlation coefficient and minimum detectable change. RESULTS: Among the three users, the mean Dice similarity coefficient, Pearson correlation, and mean difference ranged from 76.79% to 79.76%, 0.970 to 0.980 (p < 0.001), and -1.5 to -0.4 ml, respectively, for all intracranial hemorrhage segmentations. Inter-rater intraclass correlation coefficients between the three users for Dice similarity coefficient and intracranial hemorrhage volume were 0.846 and 0.962, respectively, and the corresponding minimum detectable change was 2.51 ml. Inter-rater intraclass correlation coefficient for intracranial hemorrhage volume change ranged from 0.915 to 0.958 for each user compared to manual measurements, resulting in an minimum detectable change range of 2.14 to 4.26 ml. CONCLUSIONS: We spatially and volumetrically validate a novel interactive segmentation method for delineating intracranial hemorrhage on head non-contrast CT images. Good spatial overlap, excellent volume correlation, and good repeatability suggest its usefulness for measuring intracranial hemorrhage volume and volume change on non-contrast CT images.

Association between flat-panel computed tomography hyperattenuation and clinical outcome after successful recanalization by endovascular treatment.

OBJECTIVE: Hyperattenuation on CT scanning performed immediately after endovascular treatment (EVT) is known to be associated with the final infarct. As flat-panel CT (FPCT) scanning is readily accessible within their angiography suite, the authors evaluated the ability of the extent of hyperattenuation on FPCT to predict clinical outcomes after EVT. METHODS: Patients with successful recanalization (modified Thrombolysis in Cerebral Infarction grade 2b or 3) were reviewed retrospectively. The extent of hyperattenuation was assessed by the Alberta Stroke Program Early CT Score on FPCT (FPCT-ASPECTS). FPCT-ASPECTS findings were compared according to functional outcome and malignant infarction. The predictive power of the FPCT-ASPECTS with initial CT images before EVT (CT-ASPECTS) and follow-up diffusion-weighted images (MR-ASPECTS) was also compared. RESULTS: A total of 235 patients were included. All patients were treated with mechanical thrombectomy, and 45.5% of the patients received intravenous tissue plasminogen activator. The mean (± SD) time from stroke onset to recanalization was 383 ± 290 minutes. The FPCT-ASPECTS was significantly different between patients with a favorable outcome and those without (mean 9.3 ± 0.9 vs 6.7 ± 2.6) and between patients with malignant infarction and those without (3.4 ± 2.9 vs 8.8 ± 1.4). The FPCT-ASPECTS was an independent factor for a favorable outcome (adjusted OR 3.28, 95% CI 2.12-5.01) and malignant infarction (adjusted OR 0.42, 95% CI 0.31-0.57). The area under the curve (AUC) of the FPCT-ASPECTS for a favorable outcome (0.862, cutoff ≥ 8) was significantly greater than that of the CT-ASPECTS (0.637) (p < 0.001) and comparable to that of the MR-ASPECTS (0.853) (p = 0.983). For malignant infarction, the FPCT-ASPECTS was also more predictive than the CT-ASPECTS (AUC 0.906 vs 0.552; p = 0.001) with a cutoff of ≤ 5. CONCLUSIONS: The FPCT-ASPECTS was highly predictive of clinical outcomes in patients with successful recanalization. FPCT could be a practical method to immediately predict clinical outcomes and thereby aid in acute management after EVT.

Thermal Conductivity and Electromagnetic Interference (EMI) Absorbing Properties of Composite Sheets Composed of Dry Processed Core-Shell Structured Fillers and Silicone Polymers.

This paper proposes dual-functional sheets (DFSs) that simultaneously have high thermal conductivity (TC) and electromagnetic interference (EMI) absorbing properties, making them suitable for use in mobile electronics. By adopting a simple but highly efficient dry process for manufacturing core-shell structured fillers (CSSFs) and formulating a close-packed filler composition, the DFSs show high performance, TC of 5.1 W m-1 K-1, and a -4 dB inter-decoupling ratio (IDR) at a 1 GHz frequency. Especially, the DFSs show a high dielectric breakdown voltage (BDV) of 3 kV mm-1, which is beneficial for application in most electronic devices. The DFSs consist of two kinds of CSSFs that are blended in accordance with the close-packing rule, Horsfield's packing model, and with polydimethylsiloxane (PDMS) polymers. The core materials are soft magnetic Fe-12.5%Cr and Fe-6.5%Si alloy powders of different sizes, and Al2O3 ceramic powders of a 1-µm diameter are used as the shell material. The high performance of the DFS is supposed to originate from the thick and stable shell layer and the maximized filler loading capability owing to the close-packed structure.

One-Year Outcome of Multiple Blood-Brain Barrier Disruptions With Temozolomide for the Treatment of Glioblastoma.

Introduction: To overcome the blood-brain barrier (BBB) which interferes with the effect of chemotherapeutic agents, we performed multiple disruptions of BBB (BBBD) with magnetic resonance-guided focused ultrasound on patients with glioblastoma (GBM) during standard adjuvant temozolomide (TMZ) chemotherapy [clinical trial registration no.NCT03712293 (clinicaltrials.gov)]. We report a 1-year follow-up result of BBBD with TMZ for GBM. Methods: From September 2018 to January 2019, six patients were enrolled (four men and two women, median age: 53 years, range: 50-67 years). Of the six patients, five underwent a total of six cycles of BBBD during standard TMZ adjuvant therapy. One patient underwent three cycles of BBBD but continued with TMZ chemotherapy. The 1-year follow-up results of these six patients were reviewed. Results: The mean follow-up duration was 15.17 ± 1.72 months. Two patients showed a recurrence of tumor at 11 and 16 months, respectively. One underwent surgery, and the other patient was restarted with TMZ chemotherapy due to the tumor location with a highly possibility of surgical complications. The survival rate up to 1 year was 100%, and the other four patients are on observation without recurrence. None of the six patients had immediate or delayed BBBD-related complications. Conclusion: Multiple BBBDs can be regarded as a safe procedure without long-term complications, and it seems to have some survival benefits. However, since TMZ partially crosses the BBB, a further extended study with large numbers would be needed to evaluate the benefits of BBBD resulting in an increase of TMZ concentration. This study opened a new therapeutic strategy for GBM by combining BBBD with a larger molecular agent.

Potential Role of PDGFRß-Associated THBS4 in Colorectal Cancer Development.

Colorectal cancer is a significant cause of death since it frequently metastasizes to several organs such as the lung or liver. Tumor development is affected by various factors, including a tumor microenvironment, which may be an essential factor that leads to tumor growth, proliferation, invasion, and metastasis. In the tumor microenvironment, abnormal changes in various growth factors, enzymes, and cytokines can wield a strong influence on cancer. Thrombospondin-4 (THBS4), which is an extracellular matrix protein, also plays essential roles in the tumor microenvironment and mediates angiogenesis by transforming growth factor-ß (TGFß) signaling. Platelet-derived growth factor receptor ß (PDGFRß), which is a receptor tyrosine kinase and is also a downstream signal of TGFß, is associated with invasion and metastasis in colorectal cancer. We identified that PDGFRß and THBS4 are overexpressed in tumor tissues of colorectal cancer patients, and that PDGF-D expression increased after TGFß treatment in the colon cancer cell line DLD-1. TGFß and PDGF-D increased cellular THBS4 protein levels and secretion but did not increase THBS4 mRNA levels. This response was further confirmed by the inositol 1,4,5-triphosphate receptor (IP3R) and stromal interaction molecule 1 (STIM1) blockade as well as the PDGFRß blockade. We propose that the PDGFRß signal leads to a modification of the incomplete form of THBS4 to its complete form through IP3R, STIM1, and Ca2+-signal proteins, which further induces THBS4 secretion. Additionally, we identified that DLD-1 cell-conditioned medium stimulated with PDGF-D promotes adhesion, migration, and proliferation of colon myofibroblast CCD-18co cells, and this effect was intensified in the presence of thrombin. These findings suggest that excessive PDGFRß signaling due to increased TGFß and PDGF-D in colorectal tumors leads to over-secretion of THBS4 and proliferative tumor development.

Enhanced expression of GABRD predicts poor prognosis in patients with colon adenocarcinoma.

Neurotransmitters are reported to be involved in tumor initiation and progression. This study aimed to elucidate the prognostic value of γ-aminobutyric acid type A receptor δ subunit (GABRD) in colon adenocarcinoma (COAD) using the data from The Cancer Genome Atlas (TCGA) database. The GABRD mRNA expression levels in the COAD and normal tissues were compared using the Wilcoxon rank-sum test. The correlation between clinicopathologic characteristics and GABRD expression was analyzed by Wilcoxon rank-sum test or Kruskal-Wallis test and logistic regression. The prognostic value of GABRD mRNA expression in patients with COAD was determined using the Kaplan-Meier curve and Cox regression analysis. Finally, the molecular mechanisms of GABRD in COAD were predicted by gene set enrichment analysis (GSEA). The COAD tissues exhibited higher GABRD mRNA expression levels than the normal tissues. The logistic regression analysis revealed that GABRD mRNA expression was correlated with TNM stage, N stage, M stage, and microsatellite instability (MSI) status. The Kaplan-Meier survival curve and log-rank test revealed that patients with COAD exhibiting high GABRD mRNA expression were associated with poor overall survival (OS). The multivariate analysis indicated that increased GABRD mRNA expression was an independent prognostic factor and was correlated with a poor OS. The GSEA revealed that GABRD was involved in signaling pathways, including cell adhesion molecules, gap junction, melanogenesis, and mTOR signaling pathway, as well as the signaling pathways associated with basal cell carcinoma or bladder cancer development. In summary, enhanced GABRD mRNA expression may be a potential independent prognostic biomarker for COAD.

Contrast-Enhanced High-Resolution Intracranial Vessel Wall MRI with Compressed Sensing: Comparison with Conventional T1 Volumetric Isotropic Turbo Spin Echo Acquisition Sequence.

OBJECTIVE: Compressed sensing (CS) has gained wide interest since it accelerates MRI acquisition. We aimed to compare the 3D post-contrast T1-weighted volumetric isotropic turbo spin echo acquisition (VISTA) with CS (VISTA-CS) and without CS (VISTA-nonCS) in intracranial vessel wall MRIs (VW-MRI). MATERIALS AND METHODS: From April 2017 to July 2018, 72 patients who underwent VW-MRI, including both VISTA-CS and VISTA-nonCS, were retrospectively enrolled. Wall and lumen volumes, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were measured from normal and lesion sites. Two neuroradiologists independently evaluated overall image quality and degree of normal and lesion wall delineation with a four-point scale (scores ≥ 3 defined as acceptable). RESULTS: Scan coverage was increased in VISTA-CS to cover both anterior and posterior circulations with a slightly shorter scan time compared to VISTA-nonCS (approximately 7 minutes vs. 8 minutes). Wall and lumen volumes were not significantly different with VISTA-CS or VISTA-nonCS (interclass correlation coefficient = 0.964-0.997). SNR was or trended towards significantly higher values in VISTA-CS than in VISTA-nonCS. At normal sites, CNR was not significantly different between two sequences (p = 0.907), whereas VISTA-CS provided lower CNR in lesion sites compared with VISTA-nonCS (p = 0.003). Subjective wall delineation was superior with VISTA-nonCS than with VISTA-CS (p = 0.019), although overall image quality did not differ (p = 0.297). The proportions of images with acceptable quality were not significantly different between VISTA-CS (83.3-97.8%) and VISTA-nonCS (75-100%). CONCLUSION: CS may be useful for intracranial VW-MRI as it allows for larger scan coverage with slightly shorter scan time without compromising image quality.