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Heterogeneous medium enhanced angiogr- ams are key diagnostic tools in clinical practice; the associated hemodynamic information is crucial for diagnosing cardiovascular diseases. However, the dynamics of such medium in physiological blood flow are poorly understood. Herein, we report a previously unnoticed dispersion pattern, which is a universal phenomenon, of a medium in pulsatile blood flow. We present a physical theory for studying the dispersion of a steadily injected heterogeneous medium into a thin tubular blood vessel in which the blood flow is pulsatile. In a thin tubular blood vessel, we demonstrate that variations of concentration associated with the heterogeneous medium obey a one-dimensional advection diffusion equation, and the diffusion has limited effect whenever a short vascular segment is considered. A distinct feature of the distribution of the medium in the axial distance-time plane is a "dilation-retraction" pattern. The time evolution signals at different axial positions exhibit distinct concentration waveforms. A numerical scheme is proposed for exploiting this information to estimate the pulsatile velocity. Artificial data are adopted to validate the scheme. Real X-ray angiography is also analyzed to support our theory and method. The theory is applicable whenever imaging protocols involve a heterogeneous medium in pulsatile flow.

Digital subtraction angiography (DSA) is the gold standard for diagnosing vascular diseases. Much attention had been attracted on estimating blood flow velocity from DSA data, and many techniques to compute the mean flow velocity had been proposed. In this paper, we present a physical model that demonstrates how the pulsatile flow can affect the dispersion of the contrast medium delivered into the blood vessel. Using empirical mode decomposition and angiographic data of 4 patients, we then showed it is feasible to compute pulsatile flow related parameters from routine interventional angiographic acquisitions.Clinical Relevance- This is the first attempt to present a physical model and corresponding method to estimate pulsatile flow related parameters from routine angiographic acquisitions, and has potential to be used for real-time diagnostic and therapeutic monitoring during interventional procedures.

Objective: Four-dimensional (4D) digital subtraction angiography (DSA) offers a method for evaluating hemodynamics. It is, however, unclear how the delivered contrast medium interacts with the physiological blood flow, and how hemodynamic information may be inferred from the mixture of the contrast medium and blood. In this study, we present a theoretical explanation of contrast dynamics, and an accompanying algorithm for estimating blood flow velocity., Approach: We retrospectively recruited 23 patients who underwent both 4D DSA and magnetic resonance (MR) phase-contrast imaging. The 4D DSA-reconstructed contrast dynamics were first studied for the internal carotid arteries. Using physical laws governing fluid motion within a curved tube, we showed that the reconstructed contrast dynamics obeyed a simple advection equation. We then proposed an algorithm for estimating the contrast dynamics using angiographic data, and subsequently estimated the axial blood flow velocity using an advection equation., Main Results: The estimated velocities were compared using three techniques: the Fourier technique, Lin's method, and MR phase contrast. Testing with noise-corrupted artificial data showed that the proposed algorithm was noise resistant. The velocities of 23 patients computed by 4D DSA using the proposed algorithm showed a moderate correlation with the MR phase contrast (r = 0.61), and good correlations with the other two techniques (r = 0.75 and r = 0.72)., Significance: The proposed algorithm and has been applied to blood vessel segments with poor signal-to-noise ratios and axial lengths of less than 3 cm, and has a physical basis for computing axial flow velocities using an advection equation. The results of the proposed algorithm are consistent with existing methods.

Arsenic trioxide (ATO) is an effective therapeutic agent against acute promyelocytic leukemia (APL); however, its anti-tumor effect on solid tumors such as colorectal cancer (CRC) is still in debate. Ascorbic acid (AA) also produces a selective cytotoxic activity against tumor cells. Here, we exploit the potential benefit of ATO/AA combination in generating cytotoxicity to CRC cells, which may lay the groundwork for the potential combinational chemotherapy of CRCs. According to the results, we found that ATO and AA effectively inhibited the viability of human CRC cells in a synergistic manner. AA and ATO corporately activated caspase-3 to trigger apoptosis and upregulated the expression of caspase-1 and promoted formation of inflammasomes to induce pyroptosis. Furthermore, the stimulation of reactive oxygen species (ROS) overproduction was demonstrated as a subcellular mechanism for apoptosis and pyroptosis induced by ATO/AA combination treatment. Our findings suggest that ATO combination with a conventional dosage of AA offers an advantage for killing CRC cells. The synergistic action of ATO/AA combination might be considered a plausible strategy for the treatment of CRC and perhaps other solid tumors as well., (Copyright © 2020 Tian, Wang, Tang, Li, Liu, Chu and Yang.)

Small ubiquitin-related modifiers (SUMO) represent a class of ubiquitin-like proteins that are conjugated, like ubiquitin, by a set of enzymes to form cellular regulatory proteins, and play key roles in the control of cell proliferation, differentiation, and apoptosis. We found that ginkgolic acid (GA) can significantly reduce cell vitality in a dose- and time-dependent manner and can also accelerate cyto-apoptosis in both Tca8113 and Cal-27 cells. Migration and wound-healing assays were executed to determine the anti-migration effect of GA in oral squamous cell carcinoma (OSCC) cell lines. GA represses transforming growth factor-β1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) markers in OSCC cell lines. This investigation is the first evidence that GA suppresses TGF-β1-induced SUMOylation of SMAD4. We show that GA affects the phosphorylation of SMAD2/3 protein and the release of SMAD4. In the xenograft mouse model, the OSCC progression was reduced by GA, effectively suppressing the growth of tumors. In addition, si SMAD4 improved cell migration and viability, which was inhibited by GA in Tca8113 cells. GA suppresses tumorigenicity and tumor progression of OSCC through inhibition of TGF-β1-induced enhancement of SUMOylation of SMAD4. Thus, GA could be a promising therapeutic for OSCC., (© 2019 The Author(s).)

Background: Quantitative digital subtraction angiography (DSA) facilitates in-room assessment of flow changes in various cerebrovascular diseases and improves patient safety. The purpose of this study was to compare the diagnostic accuracy of quantitative fluoroscopic angiography (FA) and DSA., Methods: Twenty-two patients with >70% carotid stenosis according to NASCET criteria were prospectively included in the study. All patients received DSA and FA (ArtisZee, Siemens Healthcare, Forchheim, Germany) before and after carotid stenting in the same angiosuite. The regions of interest (ROIs) included the extracranial internal carotid artery (eICA), first segment of the middle cerebral artery (MCA1), and sigmoid sinus in the anterior-posterior view; cavernous portion of the ICA (cICA), parietal vein, and jugular vein in the lateral views. The time-to-peak (TTP) for all ROIs and cerebral circulation time (CCT) were measured from FA and DSA scans. TTP, CCT, and radiation doses from DSA were compared with those from FA., Results: The mean age of the patients were 69 ± 9.5 years old. The average stenosis was 89.7% ± 7.8% before stenting and 31% ± 3.6% after stenting. No patient suffered from periprocedural stroke. The intermethod correlation for TTP for all ROIs except the eICA and cICA ranged from 0.46 to 0.65 before stenting and 0.57 to 0.73 after stenting, and that for CCT was 0.65 before stenting and 0.57 after stenting. The radiation doses were significantly lower for FA than for DSA regardless of views or periprocedural timing (p < 0.001)., Conclusion: Stenosis facilitated the creation of a bolus by manual injection and therefore increased the accuracy of cerebral flow quantification in FA. Cerebral hemodynamic assessment by FA is quicker and associated with less radiation.

Transforming growth factor-β (TGF-β) signaling pathway is involved in fibrosis in most, if not all forms of cardiac diseases. Here, we evaluate a positive feedback signaling the loop of TGF-β1/promyelocytic leukemia (PML) SUMOylation/Pin1 promoting the cardiac fibrosis. To test this hypothesis, the mice underwent transverse aortic constriction (3 weeks) were developed and the morphological evidence showed obvious interstitial fibrosis with TGF-β1, Pin1 upregulation, and increase in PML SUMOylation. In neonatal mouse cardiac fibroblasts (NMCFs), we found that exogenous TGF-β1 induced the upregulation of TGF-β1 itself in a time- and dose-dependent manner, and also triggered the PML SUMOylation and the formation of PML nuclear bodies (PML-NBs), and consequently recruited Pin1 into nuclear to colocalize with PML. Pharmacological inhibition of TGF-β signal or Pin1 with LY364947 (3 μM) or Juglone (3 μM), the TGF-β1-induced PML SUMOylation was reduced significantly with downregulation of the messenger RNA and protein for TGF-β1 and Pin1. To verify the cellular function of PML by means of gain- or loss-of-function, the positive feedback signaling loop was enhanced or declined, meanwhile, TGF-β-Smad signaling pathway was activated or weakened, respectively. In summary, we uncovered a novel reciprocal loop of TGF-β1/PML SUMOylation/Pin1 leading to myocardial fibrosis., (© 2018 Wiley Periodicals, Inc.)

The epithelial-mesenchymal transition (EMT) is a key event associated with metastasis and dissemination in breast tumor pathogenesis. Promyelocytic leukemia (PML) gene produces several isoforms due to alternative splicing; however, the biological function of each specific isoform has yet to be identified. In this study, we report a previously unknown role for PMLIV, the most intensely studied nuclear isoform, in transforming growth factor-β (TGF-β) signaling-associated EMT and migration in breast cancer. This study demonstrates that PMLIV overexpression promotes a more aggressive mesenchymal phenotype and increases the migration of MCF-7 cancer cells. This event is associated with activation of the TGF-β canonical signaling pathway through the induction of Smad2/3 phosphorylation and the translocation of phospho-Smad2/3 to the nucleus. In this study, we report a previously unknown role for PMLIV in TGF-β signaling-induced regulation of breast cancer-associated EMT and migration. Targeting this pathway may be therapeutically beneficial., (© 2018 Wiley Periodicals, Inc.)

Background: The efficacy of both quantitative digital subtraction angiography (QDSA) and flat-detector computed tomography perfusion (FD-CTP) is equivalent to that of magnetic resonance perfusion (MRP) in assessing perfusion deficits in carotid stenosis. This study evaluated the feasibility of using FD-CTP to monitor cerebral hemodynamics during carotid stenting., Methods: Thirteen patients with extracranial carotid stenosis (>70%) were included. Both QDSA and two FD-CTP sessions were performed before and after carotid stenting. Cerebral circulation time (CCT) was defined as the difference between the time to peak (TTP) of the parietal vein and the cavernous internal carotid artery. For FD-CTP and MRP, regions of interest (ROIs) were placed in the middle cerebral artery territory at the basal ganglia level of both stenotic and contralateral hemispheres for measurement. The TTP ratio (rTTP) was defined as stenotic TTP divided by contralateral TTP; and ratio of cerebral blood volume (rCBV), ratio of mean transit time (rMTT), and ratio of cerebral blood flow (rCBF) were defined similarly. Both CCT and ratio perfusion parameters were compared during stenting., Results: Before stenting, only rCBF (r = 0.73) and rTTP (r = 0.58) demonstrated correlations between FD-CTP and MRP; CCT correlated with only rMTT in MRP (r = 0.69). After stenting, only rCBF (r = 0.56) indicated a correlation between FD-CTP and MRP. Regarding cerebral flow after stenting, CCT (4.61 ± 1.6 s) was shortened, rMTT (1.12 ± 0.04) and rTTP (r = 1.05 ± 0.03) decreased, and rCBF (0.91 ± 0.16) increased significantly., Conclusion: FD-CTP provides a potentially more comprehensive hemodynamic assessment of parenchymal perfusion changes compared with QDSA during carotid stenting, but FC-CTP requires additional 18 min. FD-CTP confirmed that the normalization of cerebral hemodynamics began immediately and continued for 1-3 days., (Copyright © 2018. Published by Elsevier Taiwan LLC.)

Background and Purpose: PEP06, a polypeptide modified from endostatin, was investigated for its antitumour effects on colorectal cancer (CRC) and the possible mechanisms of this antitumour activity were examined in in vitro and in vivo models., Experimental Approach: After PEP06 treatment, cell proliferation and migration assays were performed in CRC cells. Epithelial-mesenchymal transition (EMT) progression was determined by Western blotting, immunofluorescent staining and immunohistochemistry in vitro and in a residual xenograft model. MiRNAs regulated by PEP06 were identified by miRNA microarray and verified by in situ hybridization and quantitative real-time PCR. The interactions between PEP06 and integrin αvβ3 were determined with Biacore SA biochips. The cellular function of miR-146b-5p was validated by gain-of-function and loss-of-function approaches. A mouse model of lung metastasis was used to determine the effect of PEP06 on metastatic growth., Key Results: PEP06 did not affect cell viability but reduced migration and EMT in SW620 and HCT116 cells. PEP06 significantly repressed the expression of miR-146b-5p in these two cell lines through binding to integrin αvβ3. MiR-146b-5p was shown to increase EMT by targeting Smad4, and the miR-146b-5p-Smad4 cascade regulated EMT in CRC. PEP06 also suppressed CRC pulmonary metastasis, increased survival of mice and hampered residual tumour growth by inhibiting EMT through down-regulating miR-146b-5p., Conclusions and Implications: PEP06 is a polypeptide that inhibits the growth and metastasis of colon cancer through its RGD motif binding to integrin αvβ3, thereby down-regulating miR-146b-5p to inhibit EMT in vitro and in vivo. It might have potential as a therapeutic for CRC., (© 2018 The British Pharmacological Society.)

Background: Time-resolved rotational angiography (t-RA) enables interventionists to better comprehend complex arteriovenous malformations (AVMs), thereby facilitating endovascular treatment. However, its use in evaluating hemodynamic changes has rarely been explored., Objective: This study uses t-RA to estimate intravascular flow in patients with AVM to compare this with flow in the normal population., Methods: Patients with available t-RA scans were prospectively categorized into one of three groups: hemorrhagic AVM, non-hemorrhagic AVM and control. Pulsatile time-density curves (TDCs) for C1, C6 and VOI MCA were used for amplitude and velocity estimation. C1 was at the cervical internal carotid artery (ICA), 2-3 cm below the carotid canal, C6 was at the paraclinoid segment of the ICA, and VOI MCA was at the junction of the first and second segment of the middle cerebral artery (MCA). A waveform amplitude ratio was defined as (peak - trough)/trough contrast intensity. V ICA was defined as the distance between C6 and C1 divided by the time required for the wave to pass, and correspondingly, the average velocity of MCA (V MCA ) was defined as the distance between C6 and VOI MCA divided by the duration for the same peak to travel from C6 and VOI MCA , AVM volume was estimated by MR angiography., Results: Amplitude ratios A C1 and A C6 , and average flow velocities V ICA and V MCA were significantly larger in the non-hemorrhagic group than in the control group, while the hemorrhagic AVM group was not significantly different from the controls. V ICA and V MCA showed moderate to good correlations with AVM volume (r=0.51 and 0.73, respectively). V MCA (33.0±9.1) was significantly lower than V ICA (41.3±13.2) in the control group, but not in the two AVM groups., Conclusion: TDC waveform propagation derived from t-RA can quantify hemodynamic differences between AVM and the control group. t-RA provides both real-time anatomic and hemodynamic evaluation, and can thus potentially improve the interventional workflow., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background and Purpose: Protein modification by small ubiquitin-like modifier (SUMO) plays a critical role in the pathogenesis of heart diseases. The present study was designed to determine whether ginkgolic acid (GA) as a SUMO-1 inhibitor exerts an inhibitory effect on cardiac fibrosis induced by myocardial infarction (MI)., Experimental Approach: GA was delivered by osmotic pumps in MI mice. Masson staining, electron microscopy (EM) and echocardiography were used to assess cardiac fibrosis, ultrastructure and function. Expression of SUMO-1, PML, TGF-β1 and Pin1 was measured with Western blot or Real-time PCR. Collagen content, cell viability and myofibroblast transformation were measured in neonatal mouse cardiac fibroblasts (NMCFs). Promyelocytic leukemia (PML) protein was over-expressed by plasmid transfection., Key Results: GA improved cardiac fibrosis and dysfunction, and decreased SUMO-1 expression in MI mice. GA (>20 μM) inhibited NMCF viability in a dose-dependent manner. Nontoxic GA (10 μM) restrained angiotensin II (Ang II)-induced myofibroblast transformation and collagen production. GA also inhibited expression of TGF-β1 mRNA and protein in vitro and in vivo. GA suppressed PML SUMOylation and PML nuclear body (PML-NB) organization, and disrupted expression and recruitment of Pin1 (a positive regulator of TGF-β1 mRNA), whereas over-expression of PML reversed that., Conclusions and Implications: Inhibition of SUMO-1 by GA alleviated MI-induced heart dysfunction and fibrosis, and the SUMOylated PML/Pin1/TGF-β1 pathway is crucial for GA-inhibited cardiac fibrosis., (Copyright © 2018. Published by Elsevier Inc.)

Purpose: Current time-density curve analysis of digital subtraction angiography (DSA) provides intravascular flow information but requires manual vasculature selection. We developed an angiographic marker that represents cerebral perfusion by using automatic independent component analysis., Materials and Methods: We retrospectively analyzed the data of 44 patients with unilateral carotid stenosis higher than 70% according to North American Symptomatic Carotid Endarterectomy Trial criteria. For all patients, magnetic resonance perfusion (MRP) was performed one day before DSA. Fixed contrast injection protocols and DSA acquisition parameters were used before stenting. The cerebral circulation time (CCT) was defined as the difference in the time to peak between the parietal vein and cavernous internal carotid artery in a lateral angiogram. Both anterior-posterior and lateral DSA views were processed using independent component analysis, and the capillary angiogram was extracted automatically. The full width at half maximum of the time-density curve in the capillary phase in the anterior-posterior and lateral DSA views was defined as the angiographic mean transient time (aMTT; i.e., aMTTAP and aMTTLat). The correlations between the degree of stenosis, CCT, aMTTAP and aMTTLat, and MRP parameters were evaluated., Results: The degree of stenosis showed no correlation with CCT, aMTTAP, aMTTLat, or any MRP parameter. CCT showed a strong correlation with aMTTAP (r = 0.67) and aMTTLat (r = 0.72). Among the MRP parameters, CCT showed only a moderate correlation with MTT (r = 0.67) and Tmax (r = 0.40). aMTTAP showed a moderate correlation with Tmax (r = 0.42) and a strong correlation with MTT (r = 0.77). aMTTLat also showed similar correlations with Tmax (r = 0.59) and MTT (r = 0.73)., Conclusion: Apart from vascular anatomy, aMTT estimates brain parenchyma hemodynamics from DSA and is concordant with MRP. This process is completely automatic and provides immediate measurement of quantitative peritherapeutic brain parenchyma changes during stenting.

The human ether-a-go-go-related gene (HERG) channel is a novel target for the treatment of drug-induced long QT syndrome, which causes lethal cardiotoxicity. This study is designed to explore the possible role of PML SUMOylation and its associated nuclear bodies (NBs) in the regulation of HERG protein expression. Both arsenic trioxide (ATO) and angiotensin II (Ang II) were able to significantly reduce HERG protein expression, while also increasing PML SUMOylation and accelerating the formation of PML-NBs. Pre-exposure of cardiomyocytes to a SUMOylation chemical inhibitor, ginkgolic acid, or the silencing of UBC9 suppressed PML SUMOylation, subsequently preventing the downregulation of HERG induced by ATO or Ang II. Conversely, knockdown of RNF4 led to a remarkable increase in PML SUMOylation and the function of PML-NBs, further promoting ATO- or Ang II-induced HERG protein downregulation. Mechanistically, an increase in PML SUMOylation by ATO or Ang II dramatically enhanced the formation of PML and Pin1 complexes in PML-NBs, leading to the upregulation of TGF-β1 protein, eventually inhibiting HERG expression through activation of protein kinase A. The present work uncovered a novel molecular mechanism underlying HERG protein expression and indicated that PML SUMOylation is a critical step in the development of drug-acquired arrhythmia.

Background: Myocardial infarction (MI) is often accompanied by cardiomyocyte apoptosis, which decreases heart function and leads to an increased risk of heart failure. The aim of this study was to examine the effects of transforming growth factor-β receptor III (TGFβR3) on cardiomyocyte apoptosis during MI., Methods and Results: An MI mouse model was established by left anterior descending coronary artery ligation. Cell viability, apoptosis, TGFβR3, and mitogen-activated protein kinase signaling were assessed by methylthiazolyldiphenyl-tetrazolium bromide assay, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, immunofluorescence, electron microscopy, and Western blotting. Our results demonstrated that TGFβR3 expression in the border region of the heart was dynamically changed during MI. After stimulation with H 2 O 2 , TGFβR3 overexpression in cardiomyocytes led to increased cell apoptosis and activation of p38 signaling, whereas TGFβR3 knockdown had the opposite effect. ERK1/2 and JNK1/2 signaling was not altered by TGFβR3 modulation, and p38 inhibitor (SB203580) reduced the effect of TGFβR3 on apoptosis, suggesting that p38 has a nonredundant function in activating apoptosis. Consistent with the in vitro observations, cardiac TGFβR3 transgenic mice showed augmented cardiomyocyte apoptosis, enlarged infarct size, increased injury, and enhanced p38 signaling upon MI. Conversely, cardiac loss of function of TGFβR3 by adeno-associated viral vector serotype 9-TGFβR3 short hairpin RNA attenuated the effects of MI in mice., Conclusions: TGFβR3 promotes apoptosis of cardiomyocytes via a p38 pathway-associated mechanism, and loss of TGFβR3 reduces MI injury, which suggests that TGFβR3 may serve as a novel therapeutic target for MI., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

The promyelocytic leukemia protein (PML) is essential in the assembly of dynamic subnuclear structures called PML nuclear bodies (PML-NBs), which are involved in regulating diverse cellular functions. However, the possibility of PML being involved in cardiac disease has not been examined. In mice undergoing transverse aortic constriction (TAC) and arsenic trioxide (ATO) injection, transforming growth factor β1 (TGF-β1) was upregulated along with dynamic alteration of PML SUMOylation. In cultured neonatal mouse cardiac fibroblasts (NMCFs), ATO, angiotensin II (Ang II), and fetal bovine serum (FBS) significantly triggered PML SUMOylation and the assembly of PML-NBs. Inhibition of SUMOylated PML by silencing UBC9, the unique SUMO E2-conjugating enzyme, reduced the development of cardiac fibrosis and partially improved cardiac function in TAC mice. In contrast, enhancing SUMOylated PML accumulation, by silencing RNF4, a poly-SUMO-specific E3 ubiquitin ligase, accelerated the induction of cardiac fibrosis and promoted cardiac function injury. PML colocalized with Pin1 (a positive regulator for TGF-β1 mRNA expression in PML-NBs) and increased TGF-β1 activity. These findings suggest that the UBC9/PML/RNF4 axis plays a critical role as an important SUMO pathway in cardiac fibrosis. Modulating the protein levels of the pathway provides an attractive therapeutic target for the treatment of cardiac fibrosis and heart failure., (Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)

Background/aims: The present study investigated whether the transient receptor potential melastatin 4 (TRPM4) channel plays a role in high salt diet (HSD)-induced endothelial injuries., Methods: Western blotting and immunofluorescence were used to examine TRPM4 expression in the mesenteric endothelium of Dahl salt-sensitive (SS) rats fed a HSD. The MTT, TUNEL, and transwell assays were used to evaluate the cell viability, cell apoptosis, and cell migration, respectively, of human umbilical vein endothelial cells (HUVECs). Enzyme-linked immunosorbent assays were used to determine the concentrations of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion protein 1 (VCAM-1), and E-selectin. Carboxy-H2DCFDA, a membrane-permeable reactive oxygen species (ROS)-sensitive fluorescent probe, was used to detect intracellular ROS levels., Results: TRPM4 was mainly expressed near the plasma membrane of mesenteric artery endothelial cells, and its expression level increased in SS hypertensive rats fed a HSD. Its protein expression was significantly upregulated upon treatment with exogenous hydrogen peroxide (H2O2) and aldosterone in cultured HUVECs. Cell viability decreased upon treatment with both agents in a concentration-dependent manner, which could be partially reversed by 9-phenanthrol, a specific TRPM4 inhibitor. Exogenous H2O2 induced apoptosis, enhanced cell migration, and increased the release of adhesion molecules, including ICAM-1, VCAM-1, and E-selectin, all of which were significantly attenuated upon treatment with 9-phenanthrol. Aldosterone and H2O2 induced the accumulation of intracellular ROS, which was significantly inhibited by 9-phenanthrol, suggesting that oxidative stress is one of the mechanisms underlying aldosterone-induced endothelial injury., Conclusions: Given the fact that oxidative stress and high levels of circulating aldosterone are present in hypertensive patients, we suggest that the upregulation of TRPM4 in the vascular endothelium may be involved in endothelial injuries caused by these stimuli., (© 2017 The Author(s)Published by S. Karger AG, Basel.)

Purpose: To quantify the arterial flow change during transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) using digital subtraction angiography, quantitative color-coding analysis (d-QCA), and real-time subtraction fluoroscopy QCA (f-QCA)., Materials and Methods: This prospective study enrolled 20 consecutive patients with HCC who had undergone TACE via a subsegmental approach between February 2014 and April 2015. The TACE endpoint was a sluggish antegrade tumor-feeding arterial flow. d-QCA and f-QCA were used for determining the relative maximal density time (rT max ) of the selected arteries. The rT max of the selected arteries was analyzed in d-QCA and f-QCA before and after TACE, and its correlation in both analyses was evaluated., Results: The pre- and post-TACE rT max of the embolized segmental artery in d-QCA and f-QCA were 1.59 ± 0.81 and 2.97 ± 1.80 s (P < 0.001) and 1.44 ± 0.52 and 2.28 ± 1.02 s (P < 0.01), respectively. The rT max of the proximal hepatic artery did not significantly change during TACE in d-QCA and f-QCA. The Spearman correlation coefficients of the pre- and post-TACE rT max of the embolized segmental artery between d-QCA and f-QCA were 0.46 (P < 0.05) and 0.80 (P < 0.001). Radiation doses in one series of d-QCA and f-QCA were 140.7 ± 51.5 milligray (mGy) and 2.5 ± 0.7 mGy, respectively., Conclusions: f-QCA can quantify arterial flow changes with a higher temporal resolution and lower radiation dose. Flow quantification of the embolized segmental artery using f-QCA and d-QCA is highly correlated.

Purpose: The aim of our study is to explore the impacts of different deconvolution algorithms on correlations between CBF, MTT, CBV, TTP, Tmax from MR perfusion (MRP) and angiography cerebral circulation time (CCT)., Methods: Retrospectively, 30 patients with unilateral carotid stenosis, and available pre-stenting MRP and angiography were included for analysis. All MRPs were conducted in a 1.5-T MR scanner. Standard singular value decomposition, block-circulant, and two delay-corrected algorithms were used as the deconvolution methods. All angiographies were obtained in the same bi-plane flat-detector angiographic machine. A contrast bolus of 12mL was administrated via angiocatheter at a rate of 8mL/s. The acquisition protocols were the same for all cases. CCT was defined as the difference between time to peak from the cavernous ICA and the parietal vein in lateral view. Pearson correlations were calculated for CCT and CBF, MTT, CBV, TTP, Tmax., Results: The correlation between CCT and MTT was highest with Tmax (r=0.65), followed by MTT (r=0.60), CBF (r=-0.57), and TTP (r=0.33) when standard singular value decomposition was used. No correlation with CBV was noted., Conclusions: MRP using a singular value decomposition algorithm confirmed the feasibility of quantifying cerebral blood flow deficit in steno-occlusive disease within the angio-room. This approach might further improve patient safety by providing immediate cerebral hemodynamics without extraradiation and iodine contrast., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Purpose: We sought to imitate angiographic cerebral circulation time (CCT) and create a similar index from baseline CT perfusion (CTP) to better predict vasospasm in patients with subarachnoid hemorrhage (SAH)., Methods: Forty-one SAH patients with available DSA and CTP were retrospectively included. The vasospasm group was comprised of patients with deterioration in conscious functioning and newly developed luminal narrowing; remaining cases were classified as the control group. The angiography CCT (XA-CCT) was defined as the difference in TTP (time to peak) between the selected arterial ROIs and the superior sagittal sinus (SSS). Four arterial ROIs were selected to generate four corresponding XA-CCTs: the right and left anterior cerebral arteries (XA-CCTRA2 and XA-CCTLA2) and right- and left-middle cerebral arteries (XA-CCTRM2 and XA-CCTLM2). The CCTs from CTP (CT-CCT) were defined as the differences in TTP from the corresponding arterial ROIs and the SSS. Correlations of the different CCTs were calculated and diagnostic accuracy in predicting vasospasm was evaluated., Results: Intra-class correlations ranged from 0.96 to 0.98. The correlations of XA-CCTRA2, XA-CCTRM2, XA-CCTLA2, and XA-CCTLM2 with the corresponding CT-CCTs were 0.64, 0.65, 0.53, and 0.68, respectively. All CCTs were significantly prolonged in the vasospasm group (5.8-6.4 s) except for XA-CCTLA2. CT-CCTA2 of 5.62 was the optimal cut-off value for detecting vasospasm with a sensitivity of 84.2% and specificity 82.4., Conclusion: CT-CCTs can be used to interpret cerebral flow without deconvolution algorithms, and outperform both MTT and TTP in predicting vasospasm risk. This finding may help facilitate management of patients with SAH.

Background and Purpose: From the time-attenuation curves of DSA flow parameters, maximal intensity, maximal slope, and full width at half maximum of selected vascular points are defined. The study explores the reliability of defining the flow parameters by the time-attenuation curves of DSA., Materials and Methods: Seventy patients with unilateral carotid artery stenosis (group A) and 56 healthy controls (group B) were retrospectively enrolled. Fixed contrast injection protocols and DSA acquisition parameters were used with all patients. The M1, sigmoid sinus, and internal jugular vein on anteroposterior view DSA and the M2, parietal vein, and superior sagittal sinus on lateral view DSA were chosen as ROI targets for measuring flow parameters. The difference of time of maximal intensity between 2 target points was defined as the circulation time between the target points., Results: The maximal intensity difference of 2 selected points from the ICA to the M1, sigmoid sinus, internal jugular vein, M2, parietal vein, and superior sagittal sinus was significantly longer in group A than in group B. The maximum slope of M1, M2, and the superior sagittal sinus was significantly lower in group A than in group B. The full width at half maximum of M1 and M2 was significantly larger in group A than in group B. The maximal slope of M1 demonstrated the best diagnostic performance., Conclusions: The maximal intensity difference of 2 selected points derived from DSA can be used as a definitive alternative flow parameter for intracranial circulation time measurement. Maximal slope and full width at half maximum complement the maximal intensity difference of 2 selected points in defining flow characteristics of healthy subjects and patients with carotid stenosis., (© 2015 by American Journal of Neuroradiology.)