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BACKGROUND Noninvasive blood oxygen level-dependent imaging and intravoxel incoherent motion sequences were used to assess bilateral renal oxygenation, hemodynamics, and proton diffusion in iodixanol renal artery first-pass in rabbit model. METHODS Forty-two rabbits were divided into 2 groups. Saline and iodixanol (1 g iodine/kg, left renal artery) were administered. Magnetic resonance imaging scans were acquired longitudinally at 24 hours prior to and 1, 24, 48, and 72 hours after administration to assess apparent diffusion coefficient, pure molecular diffusion (D), perfusion-related diffusion (D*), volume fraction (f), and relative spin-spin relaxation rate (R2*) values, respectively. The experiment evaluated serum creatinine, histological, and hypoxia-inducible factor 1α immunoexpression. RESULTS During 1 to 48 hours, the values of D, f, and D* significantly decreased (P < 0.05), but R2* values significantly increased (P < 0.05) in cortex, outer medulla, and inner medulla after administration of iodixanol through left renal artery, which showed in the 72 hours. The change of the left kidney is noteworthy. Significant negative correlations were observed between apparent diffusion coefficient, D, f, and R2* in cortex, outer medulla, and inner medulla (all P < 0.001, r = -0.635-0.697). CONCLUSIONS The first-pass effect of the contrast agent significantly reduces ipsilateral renal perfusion and renal oxygenation, and noninvasive monitoring can be performed by using blood oxygen level-dependent magnetic resonance imaging and intravoxel incoherent motion.

Fluorescence (FL) and X-ray computed tomography (CT) imaging-guided photodynamic therapy (PDT) can provide a powerful theranostic tool to visualize, monitor, and treat cancer and other diseases with enhanced accuracy and efficacy. Methods: In this study, clinically approved iodinated CT imaging contrast agent (CTIA) iodixanol and commercially available photosensitizer (PS) meso-tetrakis (4-sulphonatophenyl) porphine (TPPS4) were co-encapsulated in biocompatible PEGylated nanoliposomes (NL) for enhanced anticancer PDT guided by bimodal (FL and CT) imaging. Results: The NL co-encapsulation of iodixanol and TPPS4 (LIT) lead to an increase in singlet oxygen generation by PS via the intraparticle heavy-atom (iodine) effect on PS molecules, as it was confirmed by both direct and indirect measurements of singlet oxygen production. The confocal imaging and PDT of cancer cells were performed in vitro, exhibiting the cellular uptake of TPPS4 formulations and enhanced PDT efficacy of LIT. Meanwhile, bimodal (FL and CT) imaging was also conducted with tumor-bearing mice and the imaging results manifested high-efficient accumulation and retention of LIT in tumors. Moreover, PDT of tumor in vivo was shown to be drastically more efficient with LIT than with other formulations of TPPS4. Conclusion: This study demonstrated that LIT can serve as a highly efficient theranostic nanoplatform for enhanced anticancer PDT guided by bimodal (FL and CT) imaging.

Background: It is yet not clear whether differences in the contrast medium may affect post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). Aim: The aim of this study was to evaluate the rate of PEP between high osmolality contrast medium (HOCM) and iso osmolar medium (IOCM) in a prospective, randomized, controlled trial. Methods: Patients who were scheduled to undergo a diagnostic or therapeutic procedure under ERCP guidance were included. Patients were excluded from this study if they (1) were < 20 years old; (2) had acute or active pancreatitis; (3) had previously undergone ERCP; (4) had surgical altered upper gastrointestinal tract anatomy; or (5) refused to be involved in this study. Results: Seventy-five patients were randomly assigned to the IOCM group, and 71 patients were assigned to the HOCM group. PEP occurred in 27 patients (18.5%). Although there were no significant differences, the severe grade of PEP was more frequent in the HOCM group than in the IOCM group (p = 0.08). The results of the multivariate analyses for PEP were not identified as independent risk factors. Also, independent risk factors of hyperamylasemia were performing pre-cut. In subgroup analyses, HOCM was an independent risk factor for hyperamylasemia. Conclusions: In conclusion, HOCM may play a role in the development of PEP and in PEP severity grade.

Background There is controversy as to whether iso-osmolar contrast media (IOCM) are associated with lower risk of contrast-induced acute kidney injury (CI-AKI), compared with low-osmolar contrast media (LOCM). We aimed to evaluate if a differential risk of CI-AKI exists after percutaneous coronary intervention (PCI) according to different contrast media (CM) types. Methods We performed a single-center retrospective study in a cohort of all-comers undergoing PCI between January 2012 and December 2016. CI-AKI was defined as an increase in serum creatinine ≥0.3 mg/dl or ≥50% within 72 h from PCI. IOCM were represented by iodixanol, whereas four different LOCM were utilized (ioversol, iopromide, iomeprol, iobitridol). Multiple-treatment inverse probability of treatment weighting (IPTW)-adjusted logistic regression analysis was performed to identify whether CM type was an independent predictor of CI-AKI. Results We included 2648 subjects (ioversol, n = 272; iopromide, n = 818; iomeprol, n = 611; iobitridol, n = 460; iodixanol, n = 487). CI-AKI occurred in 300 patients (11.7%) overall, with no differences across CM groups (ioversol 13.0%, iopromide 11.5%, iomeprol 10.2%, iobitridol 13.9%, iodixanol 11.3%; p = 0.42). CI-AKI requiring dialysis was observed in 8 patients (0.3%) overall (p = 0.50). On IPTW-adjusted analysis, none of the LOCM was associated with a significantly different risk of CI-AKI compared with iodixanol: ioversol OR 0.986 (95% confidence interval [CI] 0.611–1.591), iopromide OR 0.870 (95% CI 0.606–1.250), iomeprol OR 0.904 (95% CI 0.619–1.319), iobitridol OR 1.258 (95% CI 0.850–1.861). Conclusions In a large cohort of all-comers undergoing PCI, there were no differences in the adjusted risk of CI-AKI across 4 LOCM, compared with iodixanol.

A formulation superior in absorption compared to any biological tissue, including bone one, has been obtained by immobilization of radiopaque substance iodixanol on the surface of magnetic nanoparticles.

Funding Acknowledgements Type of funding sources: None. Aims To safely perform angioplasties in acute coronary syndromes with very low contrast volume using Cordis diagnostic catheters and thereby improve the cardiovascular and renal outcomes. Methods and results In 1432 patients (1857 lesions/ 2148 stents) with acute coronary syndromes, angioplasty was performed with Cordis 6F diagnostic catheters. Primary angioplasty was performed in 457 cases. In 76% of cases, iodixanol was used. All contrast injections were given by hand. A regular follow-up of the patients was performed 30 days after the procedure. All the procedures were performed through the femoral route. Tirofiban was used in 99% cases with adjusted dosages based on the creatinine values. The mean contrast volume used per patient was 28 ml (±6 ml) including the angiogram prior to the angioplasty. Ninety one patients had creatinine more than 2mg/dl before the angioplasty procedures. Left main angioplasty was performed in 37 patients using single stents. 70 patients had cardiogenic shock at presentation. 76% of the cases had diabetes. IVUS was used in only two patients. A variety of coronary stents from various companies were used. Buddy wires were used in 36 cases. Ticagrelor was used in 92 cases, and in other cases clopidogrel was used. Mild reversible nephropathy (CIN) was observed in six patients. Four patients were already on dialysis, and dialysis was continued thereafter. Switch-over of angioplasty to the radial route was performed in five cases due to associated aortic/iliac obstructive lesions. 26 deaths in total were observed in this series; 16 of these patients had cardiogenic shock (7 late presenters), and three patients expired after discharge due to possible acute stent thrombosis. Groin haematoma was seen in five cases requiring one unit of blood transfusion. Proximal mild edge dissection in the deployed stent was seen in 3 cases which were treated with stents. Wire breakages were not seen. Acute in-hospital stent thrombosis was seen in 6 cases, which were managed with balloon dilatations and stents. Covid19 was positive in 16 cases by RT PCR. Conclusions Angioplasty and stenting can be performed safely in patients with acute coronary syndromes using Cordis diagnostic catheters and a very low volume of contrast with improved clinical outcomes.

A common cause of drug hypersensitivity reactions is iodinated contrast media (ICM). ICM-induced hypersensitivity had been considered to be a non-immunological reaction, but evidence for an immunological mechanism has increased recently. Thus, we evaluated whether HLA-A, -B, and -C alleles were associated with ICM-induced hypersensitivity. In total, 126 patients who underwent contrast-enhanced computed tomography studies through outpatient clinics at a tertiary referral hospital between 2008 and 2012 were assessed. Sixty-one patients experienced ICM-induced hypersensitivity and the remainder, 65, were ICM-tolerant patients (control). ICM-induced hypersensitivity patients showed 51 with immediate, 7 with non-immediate, 3 with both or mixed type. HLA-A, -B, and -C genotyping was performed using a PCR sequence-based typing method. Four kinds of ICM were used: iopromide, iohexol, iobitridol, and iodixanol. The most used ICM among the hypersensitivity patients was iopromide. Significant difference in the frequency of HLA-B*58:01 (odds ratios [OR], 3.90; p = 0.0200, 95% confidence interval [CI], 1.16-13.07) was observed between ICM-induced immediate hypersensitivity and control. There were statistically significant differences in the frequencies of the HLA-B*38:02 (OR, 10.24; p = 0.0145; 95% CI, 1.09-96.14) and HLA-B*58:01 (OR, 3.98; p = 0.0348; 95% CI, 1.03-15.39) between iopromide-induced immediate hypersensitivity and control. The mechanism of ICM-induced hypersensitivity remains unknown, but this study showed associations, although weak, with HLA-B*58:01 alleles for ICM-induced immediate hypersensitivity and HLA-B*38:02 and HLA-B*58:01 for iopromide-induced immediate hypersensitivity as risk predictors. Further studies are needed to validate the associations in larger samples and to identify the functional mechanism behind these results.

PURPOSE Investigate the impact of nonionic dimer and monomer on iodine quantification in different vessel sizes when employing a vascular specific phantom and varying iodinated contrast media (ICM) concentrations during computed tomography (CT). MATERIALS AND METHODS We created a vascular specific phantom (30 cm) to simulate human blood vessel diameters (25 cylinders of different diameters: 10 × 9mm, 10 × 12mm and 5 × 21mm). The phantom was filled with two ICM separately: Group: Iohexol(monomer)350 mg ml-1 and B: Iodixanol(Dimer)320 mg ml-1. Cylinders of same size were filled with increasing ICM concentration(10%-100%) while large cylinders were filled in quartiles(25%-100%). Phantom was scanned with different tube potential (80-140kVp), current (50-400mAs), reconstruction method [filtered back projection (FBP), hybrid-based iterative reconstruction (HBIR) and model-based iterative reconstruction (MBIR)] for each ICM. Chi-square was employed to compare mean opacification, contrast/noise ratio (CNR) and noise. Qualitative analysis was assessed by Visual grading characteristic (VGC) and Cohens-kappa analyses. RESULTS At 80 and140kVp significant difference in opacification between Group A (2054 ± 1040HU and 1696 ± 1027HU) and B (2169 ± 1105HU and 1568 ± 1034HU) was demonstrated (p 0.05). When comparing image noise, it was higher in Group A compared to B (p

Contains fulltext : 245663.pdf (Publisher’s version ) (Open Access) BACKGROUND AND AIMS: Colchicine reduces the risk of cardiovascular events in patients with coronary disease. Colchicine has broad anti-inflammatory effects and part of the atheroprotective effects have been suggested to be the result of NLRP3 inflammasome inhibition. We studied the effect of colchicine on extracellular vesicle (EV) NLRP3 protein levels and inflammatory markers, high sensitivity-CRP (hs-CRP) and interleukin (IL)-6, in patients with chronic coronary disease. METHODS: In vitro, the NLRP3 inflammasome was stimulated in PMA-differentiated- and undifferentiated THP-1 cells. In vivo, measurements were performed in serum obtained from 278 participants of the LoDoCo2 trial, one year after randomization to colchicine 0.5 mg once daily or placebo. EVs were isolated using precipitation. NLRP3 protein presence in EVs was confirmed using iodixanol density gradient centrifugation. Levels of NLRP3 protein, hs-CRP and IL-6 were measured using ELISA. RESULTS: In vitro, NLRP3 inflammasome stimulation showed an increase of EV NLRP3 protein levels. EV NLRP3 protein levels were lower in patients treated with colchicine (median 1.38 ng/mL), compared to placebo (median 1.58 ng/mL) (p = 0.025). No difference was observed in serum NLRP3 protein levels. Serum hs-CRP levels were lower in patients treated with colchicine (median 0.80 mg/L) compared to placebo (median 1.34 mg/L) (p

Iodine is a contrast agent which has been used for a long time. Ionic and non-ionic iodine-based contrast agents are commonly used in radiology because of their fewer adverse effects. Iohexol, iodixanol and ioversol are the most used iodinated organic molecules. Physicochemical properties (viscosity, osmolality) of modern iodinated contrast agents can vary on their chemical structures (such as monomeric or dimeric), iodine contents and their ionic or non-ionic characteristics. Atropisomer chirality may affect properties such as pharmacokinetics and toxicity. Their physicochemical properties determine their pharmacokinetics, tolerability and side effects. It is known that most iodinated contrast agents are not possible to enter into an intact blood-brain barrier. Non-ionic iodinated contrast agents are thought to have lower osmolality and tend to have fewer side effects.

Grafts based on biodegradable polymer scaffolds are increasingly used in tissue-engineering applications as they facilitate natural tissue regeneration. However, monitoring the position and integrity of these scaffolds over time is challenging due to radiolucency. In this study, we used an electrospinning method to fabricate biodegradable scaffolds based on polycaprolactone (PCL) and iodixanol, a clinical contrast agent. Scaffolds were implanted subcutaneously into C57BL/6 mice and monitored in vivo using longitudinal X-ray imaging and micro-computed tomography (CT). The addition of iodixanol altered the physicochemical properties of the PCL scaffold; notably, as the iodixanol concentration increased, the fiber diameter decreased. Radiopacity was achieved with corresponding signal enhancement as iodine concentration increased while exhibiting a steady time-dependent decrease of 0.96% per day in vivo. The electrospun scaffolds had similar performance with tissue culture-treated polystyrene in supporting the attachment, viability, and proliferation of human mesenchymal stem cells. Furthermore, implanted PCL-I scaffolds had more intense acute inflammatory infiltrate and thicker layers of maturing fibrous tissue. In conclusion, we developed radiopaque, biodegradable, biocompatible scaffolds whose position and integrity can be monitored noninvasively. The successful development of other imaging enhancers may further expand the use of biodegradable scaffolds in tissue engineering applications.

Over the past 120 years, continuous developments in medical imaging has improved diagnosis and treatment for many diseases and has thereby improved treatment outcome and quality of life of many patients. The number of computed tomography (CT) examinations is today increasing by 4% per year worldwide, for a total of approximately 300 million CT scans per year. About 40% of CT scans are contrast enhanced. Intravenous iodinated contrast media are commonly used for contrast enhancement in CT scans to evaluate diseases and determine treatment response. The current gold standards for intravenous x-ray contrast media in CT or interventional angiography are iodinated low- and iso-osmolar compounds such as iopromide, iohexol, or iodixanol. Both classes have similar and favorable efficacy and safety profiles. Although iodine is biologically inert, iodinated contrast media can cause adverse reactions. In the future, one possibility would be to develop iodine-free contrast media that are better suited to higher x-ray tube voltage ranges, allowing greater flexibility for scanning protocols and thus leading to techniques that can provide equivalent diagnostic value at lower doses of radiation. Iodine-free contrast media would in addition provide an alternative to the market standard that could offer benefits for patients with known reactions to low-osmolality contrast media or thyroid disorders. The development of a new contrast medium, however, needs to be put in context with all upcoming technological advances in x-ray and CT. New detector technologies and artificial intelligence algorithms will in the future also improve the CT image reconstruction enabling the reduction of contrast media and radiation doses.

Membrane vesicles (MVs) play biologically important roles in Gram-positive bacteria, and purification is essential for their study. Although high-performance flow cytometry has the capability to quantify and isolate specific small particles, it has not been examined for MV isolation. In this study, we used high-performance flow cytometry to analyze MV from Gram-positive bacteria, Staphylococcus aureus and Bacillus subtilis, prepared by iodixanol density-gradient ultracentrifugation. Analysis of the quality of MV samples before and after sorting showed that the flow cytometric sorting provided higher purity and uniformity compared to gradient isolation alone. The MV purification method using flow cytometry should prove useful for applications requiring a very high purity of MV samples such as proteomic, metagenomic or lipidomic studies.

Purpose Magnetic resonance imaging (MRI) contrast agents have been used off-label for diagnosis of cerebrospinal fluid (CSF) leaks and lately also for assessment of the glymphatic system and meningeal lymphatic drainage. The purpose of this study was to further evaluate the short- and long-term safety profile of intrathecal MRI contrast agents. Methods In this prospective study, we compared the safety profile of different administration protocols of intrathecal gadobutrol (GadovistTM; 1.0 mmol/ml). Gadobutrol was administered intrathecal in a dose of 0.5 mmol, with or without iodixanol (VisipaqueTM 270 mg I/ml; 3 ml). In addition, a subgroup was given intrathecal gadobutrol in a dose of 0.25 mmol. Adverse events were assessed at 1 to 3 days, 4 weeks, and after 12 months. Results Among the 149 patients, no serious adverse events were seen in patients without history of prior adverse events. The combination of gadobutrol with iodixanol did not increase the occurrence of non-serious adverse events after days 1–3. Intrathecal gadobutrol in a dose of 0.25 mmol caused less severity of nausea, as compared with the dose of 0.5 mmol. The clinical diagnosis was the major determinant for occurrence of non-serious adverse events after intrathecal gadobutrol. Conclusion This prospective study showed that intrathecal administration of gadobutrol in a dose of 0.5 mmol is safe. Non-serious adverse events were to a lesser degree affected by the administration protocols, though preliminary data are given that side effects of intrathecal gadobutrol are dose-dependent.

The primary aim of the study was to investigate whether iodixanol and trehalose would have a synergic effect on the cryosurvival of electroejaculated ram semen. Tris-based diluter was used to prepare 9 different extenders by the addition of iodixanol or trehalose alone or varying combinations of these substances. Diluters were prepared as follows: Tris (control), Io5 (5% iodixanol), Tr25 (25 mmol/L trehalose), Tr50 (50 mmol/L trehalose), Tr50 + Io1.25 (50 mmol/L trehalose and 1.25% iodixanol), Tr50 + Io2.5 (50 mmol/L trehalose and 2.5% iodixanol), Tr50 + Io5 (50 mmol/L trehalose and 5% iodixanol), Tr25 + Io5 (25 mmol/L trehalose and 5% iodixanol) and Tr12.5 + Io5 (12.5 mmol/L trehalose and 5% iodixanol). Supplementation of the freezing extender with trehalose or iodixanol alone supported the protection of both morphological and functional integrity of ram spermatozoa and total motility at 1 and 4 hr post-thawing respectively. However, beyond these positive effects, the combination of trehalose (25 mmol/L) and iodixanol (5%) significantly increased post-thaw sperm longevity and motion properties at the end of 4-hr incubation. The results of the study clearly showed that there was positive synergic effect of iodixanol and trehalose on cryosurvival of ram semen.

Intrathecal administration is an important route for drug delivery, and in pharmacology and toxicology studies, cerebrospinal fluid (CSF) collection and analysis is required for evaluating blood–brain barrier penetration and central nervous system exposure. The characteristics of CSF in commonly used nonrodent models are lacking. The purpose of this study is to evaluate and provide some insights into normal cellular and biochemical composition of CSF as well as diffusion potential following intrathecal injection across several nonrodent species. Cerebrospinal fluid samples were collected from the cerebellomedullary cistern of beagle dogs, cynomolgus monkeys, and Göttingen minipigs and analyzed for clinical chemistry and cytological evaluation. Diffusion into the intrathecal space following intrathecal injection was assessed following administration of a contrast agent using fluoroscopy. The predominant cell types identified in CSF samples were lymphocytes and monocytoid cells; however, lymphocytes were represented in a higher percentage in dogs and monkeys as opposed to monocytoid cells in minipigs. Clinical chemistry parameters in CSF revealed higher Cl− concentrations than plasma, but lower K+, Ca2+, phosphorus, glucose, creatinine, and total protein levels consistent across all 3 species. Diffusion rates following intrathecal injection of iodixanol showed some variability with dogs, showing the greatest diffusion distance; however, the longest diffusion time through the intervertebral space, followed by monkeys and minipigs. Minimal diffusion was observed in minipigs, which could have been attributed to anatomical spinal constraints that have been previously identified in this species.

Background Contrast-induced encephalopathy (CIE) is a rare complication of cardiac catheterization; clinical manifestations include cortical blindness, seizures and focal neurological deficits. In general, recurrent epileptic seizures following cardiac catheterization with iodixanol occur more rarely than do other complications. Case presentation Here, we report a case of a 76-year-old male patient who experienced unstable angina for nearly 10 months and was admitted to our hospital. Repeat cardiac catheterization was performed using iodixanol. At approximately 20 h after the first cardiac catheterization, his upper limbs began to exhibit slight trembling; the patient was conscious and could not control these movements. A total of 6 episodes occurred before the second cardiac catheterization was performed, with each episode lasting approximately 2 s. These symptoms were not treated. At approximately 2 h after the second cardiac catheterization, the symptoms became more severe, and the frequency of the episodes increased significantly; the symptoms had fully subsided at 6 h after the second operation. An electroencephalogram (EEG) demonstrated diffuse slowing with epileptiform abnormalities. Paroxysmal spike-wave and slow wave discharges were observed in the bilateral areas, and the abnormalities were marked in the frontal areas. These observations led us to conclude that the patient was experiencing epileptic seizures. During 6 months of monthly clinical follow-up visits after discharge, no abnormalities of the nervous system were found by cardiologists or neurologists, and the patient’s EEG was normal. No antiepileptic drugs were administered throughout this process. Conclusions CIE, especially recurrent epileptic seizures, is a rare but often reversible complication of cardiac catheterization with iodixanol. Its symptoms can be mild and therefore are easily ignored by physicians. Early CIE detection may be achieved by EEG. Repeated exposure to contrast agents carries the risk of recurrent epileptic seizures.

Background: After application of iodinated contrast media (CM), a pronounced deterioration of the microcirculation in skin and myocardium was reported. Clinically, the repeated application of CM, especially, led to an increase of the renal resistance index (RRI). With respect to the transiency of the RRI increase, it is reasonable to assume that the deterioration of blood flow could be due to transient blood stasis caused by reversible morphologic cell alterations due to osmotic discrepancies between CM and human blood. Therefore, the hypothesis was investigated whether CM are able to induce in vivo such blood stasis and cell deformations in the renal vasculature of well-hydrated pigs. Methods: The in vivo study was performed as a prospective randomized examination to compare the effects of two different CM in 16 pigs (German Landrace). Pigs were randomized to receive either Iodixanol (n = 8), or Iopromide (n = 8). Each animal received 10 injections separated by 5-min intervals via the suprarenal aorta at a rate of 10 mL/s according to the usual procedure during a cardiac catheter examination. Finally, the kidneys were explanted and processed for histology (H & E staining and fibrin staining according to Weigert) as well as for scanning electron microscopy (SEM) with regards to morphologic correlates explaining the changes in the microcirculation. Results: In each of the predefined four categories of vascular diameters, blood stasis were found, but clearly more often after application of Iopromide than after application of Iodixanol (p < 0.001). In addition, Iopromide induced more blood stasis in all of the examined kidney regions compared to Iodixanol (p = 0.0001). There were no obstructive events in the middle cortex following the application of Iodixanol. Except for the region around a puncture channel of a placed-in catheter probe, no fibrin was detected in Weigert’s fibrin-stained samples, neither around the histologically assessed thrombi nor in vessels with blood stasis. Complementary SEM analyses revealed in a few cases only a slight generation of fibrin and thrombi and deformations, such as echinocyte and “box-like” deformations. Conclusions: According to previous in vitro studies, pathological erythrocyte deformations, such as echinocyte and box-like formation of erythrocytes, were observed also in vivo. In addition, blood stasis and/or thrombi could be detected in histological samples from explanted kidneys from young pigs after repeated in vivo administration of CM. In only a few cases, mural platelet aggregates within minimal fibrin meshes occurred only after the application of Iopromide.

Grafts based on biodegradable polymer scaffolds are increasingly used in tissue-engineering applications as they facilitate natural tissue regeneration. However, monitoring the position and integrity of these scaffolds over time is challenging due to radiolucency. In this study, we used an electrospinning method to fabricate biodegradable scaffolds based on polycaprolactone (PCL) and iodixanol, a clinical contrast agent. Scaffolds were implanted subcutaneously into C57BL/6 mice and monitored in vivo using longitudinal X-ray imaging and micro-computed tomography (CT). The addition of iodixanol altered the physicochemical properties of the PCL scaffold; notably, as the iodixanol concentration increased, the fiber diameter decreased. Radiopacity was achieved with corresponding signal enhancement as iodine concentration increased while exhibiting a steady time-dependent decrease of 0.96% per day in vivo. The electrospun scaffolds had similar performance with tissue culture-treated polystyrene in supporting the attachment, viability, and proliferation of human mesenchymal stem cells. Furthermore, implanted PCL-I scaffolds had more intense acute inflammatory infiltrate and thicker layers of maturing fibrous tissue. In conclusion, we developed radiopaque, biodegradable, biocompatible scaffolds whose position and integrity can be monitored noninvasively. The successful development of other imaging enhancers may further expand the use of biodegradable scaffolds in tissue engineering applications.

Objectives: The goal of this study was to assess the diagnostic performance of coronary computed tomography angiography (CTA) alone, adenosine-stress myocardial perfusion assessed by computed tomography (CTP) alone, and coronary CTA + CTP by using a 16-cm Z-axis coverage scanner versus invasive coronary angiography (ICA) and fractional flow reserve (FFR) as the clinical standard. Background: Diagnostic performance of coronary CTA for in-stent restenosis detection is still challenging. Recently, CTP showed additional diagnostic power over coronary CTA in patients with suspected coronary artery disease. However, few data are available on CTP performance in patients with previous stent implantation. Methods: Consecutive stable patients with previous coronary stenting referred for ICA were enrolled. All patients underwent stress myocardial CTP and rest CTP + coronary CTA. Invasive FFR was performed during ICA when clinically indicated. The diagnostic rate and diagnostic accuracy of coronary CTA, CTP, and coronary CTA + CTP were evaluated in stent-, territory-, and patient-based analyses. Results: In the 150 enrolled patients (132 men; mean age 65.1 ± 9.1 years), the CTP diagnostic rate was significantly higher than that of coronary CTA in all analyses (territory based [96.7% vs. 91.1%; p < 0.0001] and patient based [96% vs. 68%; p < 0.0001]). When ICA was used as gold standard, CTP diagnostic accuracy was significantly higher than that of coronary CTA in all analyses (territory based [92.1% vs. 85.5%, p < 0.03] and patient based [86.7% vs. 76.7%, p < 0.03]). The concordant coronary CTA + CTP assessment exhibited the highest diagnostic accuracy values versus ICA (95.8% in the territory-based analysis). The diagnostic accuracy of CTP was significantly higher than that of coronary CTA (75% vs. 30.5%; p < 0.001). The radiation exposure of coronary CTA + CTP was 4.15 ± 1.5 mSv. Conclusions: In patients with coronary stents, CTP significantly improved the diagnostic rate and accuracy of coronary CTA alone compared with both ICA and invasive FFR as gold standard.

Adeno-associated virus (AAV) is one of the most promising gene therapy vectors and is widely used as a gene delivery vehicle for basic research. As AAV continues to become the vector of choice, it is increasingly important for new researchers to have access to a simplified production and purification protocol for laboratory grade recombinant AAV. Here we report a detailed protocol for serotype independent production of AAV using a helper-free HEK293 cell system followed by iodixanol gradient purification, a method described earlier.1 While the core principals of this mammalian AAV production system are unchanged, there have been significant advancements in the production and purification procedure that serve to boost yield, maximize efficiency, and increase the purity of AAV preps. Using this protocol, we are able to constantly obtain high quantities of laboratory grade AAV particles (>5 × 1012 vg) in a week’s time, largely independent of serotype.

BackgroundPostmortem coronary angiography has been used in forensic medicine for several decades but its use has never been documented in neonatal hearts. The objective of this case is to report the use of postmortem coronary angiography as a diagnostic modality for neonates suspected to have complex congenital heart anomalies.Case presentationA 36-week-old female infant required extracorporeal membranous oxygenation for persistent hypotension on day 1 of life. A congenital echocardiogram (ECHO) on day 3 of life revealed multiple anomalous vascular structures within the interventricular septum. The infant passed away on day 4 of life after the parents elected to withdraw support. A consent for autopsy was taken from the parents and a postmortem coronary angiography was performed. The coronary vessels were injected with Iodixanol contrast via a 24 G angiocath under fluoroscopy. The anomalous septal vessels were identified as dilated coronary artery and vein. No other anomalies were identified.ConclusionPostmortem coronary angiography complements other imaging procedures in understanding the nature of some complex congenital heart defects and in determining the cause of death in such neonates.

Graphical abstract, Highlights • Iobitridol (xenetix), iodixanol (visipaque), iohexol (omnipaque), ioxaglate (hexabrix), and isovue (iopamiro), iodinated radiographic contrast media: did not show in DPPH• radical-scavenging activity; did not show ferric reducing ability property, except for iobitridol at 200 mgI/mL and ioxaglate at 50–200 mgI/mL, showed ABTS•+ radical-scavenging activity. • In conclusion, iobitridol, iodixanol, iohexol, ioxaglate, and isovue exhibited weak in vitro antioxidant properties., This study reveals the antioxidant properties of iodinated radiographic contrast media to be used in diagnostic radiology. Di(phenyl)-(2,4,6-trinitrophenyl) iminoazanium (DPPH), ferric reducing ability of plasma (FRAP), and 2,2′-azino-bis (3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) assays were used for determining in vitro the antioxidant properties of five iodinated radiographic contrast media such as iobitridol (xenetix), iodixanol (visipaque), iohexol (omnipaque), ioxaglate (hexabrix), and isovue (iopamiro). An ascorbic acid and Trolox solution served as a positive control. The absorbance intensity of the colored product was recorded using a spectrophotometer. For DPPH and ABTS assay, the absorbance intensity at 533 and 752 nm, respectively was decreased when compared to control; it indicated an increase in antioxidant activity. For FRAP assay, the absorbance intensity at 593 nm was increased when compared to control; it indicated an increase in antioxidant activity. The results showed that five iodinated radiographic contrast media did not differ in DPPH• radical-scavenging activity when compared to a corresponding control. The ferric reducing ability of all of these iodinated radiographic contrast media also did not differ when compared to a corresponding control, except for iobitridol at 200 mgI/mL and ioxaglate at 50–200 mgI/mL. All iodinated radiographic contrast media showed ABTS•+ radical-scavenging activity. This finding suggested that iobitridol, iodixanol, iohexol, ioxaglate, and isovue exhibited weak in vitro antioxidant properties. The antioxidant ability depended on the type of free radical production and the concentration of iodinated radiographic contrast media.

Purpose. The purposes of this study are to assess the acute effects of iodixanol, an iso-osmolar contrast media, on pulmonary functions and to evaluate the body composition in order to find out its role in causing this deterioration. Methods. 35 male and 25 female patients undergoing diagnostic coronary angiography (CA) were enrolled in the study. Before CA, all patients’ body compositions were evaluated by measuring their body mass indexes (BMIs) and waist-to-hip ratios (WHRs). Total body waters (TBWs), fat masses (FMs), fat-free masses (FFMs), and basal metabolism rates (BMRs) were measured via bioimpedance analysis. The CA was performed via radial artery route using iodixanol in every patient. The pulmonary function tests of these patients were performed before, during, and 2 hours after the CA. FEV1∆, FEF25–75%∆, and FVC∆ parameters were calculated by subtracting the measured baseline value from the measurement after the CA. Results. Angiography caused significant reduction in forced expiratory volume in 1 sec (FEV1, from 94.17 ± 18.83 to 84.45 ± 18.31, p<0.0001), forced vital capacity (FVC, from 96.57 ± 15.82 to 88.31 ± 17.96, p<0.0001), and forced expiratory flow at 25–75% (FEF25–75% from 82.54 ± 24.26 to 72.11 ± 25.41, p=0.001) and remained lower after 2 h after CA in male patients, respectively. FEV1 values were 103.40 ± 17.79 to 94.96 ± 17.063 (p=0.004); FVC values were 107.20 ± 19.03 to 99.08 ± 20.56 (p=0.009); and FEF25–75% values were 83.92 ± 24.30 to 73.24 ± 20.45 (p=0.005) before and after CA and remained lower after 2 h after CA in female patients, respectively. FEV1/FVC ratio remained unchanged. FEF25–75%∆ was statistically correlated with FFM, TBW, and WHR (p<0.05; r=−0.344, r=−0.347, and r=0.357, resp.), and FVC∆ was correlated with WHR in male patients (p=0.018, r=397). Conclusions. Our data suggested that diagnostic CA using iodixanol, an iso-osmolar contrast media, leads significant impairment in respiratory functions. Due to the persistence of these reductions even 2 hours after CA, ventilatory functions should be considered especially in patients whose body compositions or hydration levels are not within the desired physiological range.

To investigate the feasibility of low-concentration contrast media (LC-CM) in cerebral and cervical dual-energy CT angiography (DE-CTA) using an advanced monoenergetic (Mono+) reconstruction technique. Sixty-five consecutive patients prospectively selected to undergo cerebral and cervical DE-CTA were randomised into two groups: 32 patients (63.7 ± 9.7 years) in the high-concentration contrast medium (HC-CM) group with iopromide 370 and 33 patients (60.7 ± 10.8 years) in the low-concentration contrast medium (LC-CM) group with iodixanol 270. Traditional monoenergetic (Mono) and Mono+ images from 40 to 100 keV levels (at 10-keV intervals) and the standard mixed (Mixed, 120 kVp equivalent) images were reconstructed. Subjective image quality parameters included the contrast-to-noise ratio (CNR) and objective image quality parameters were evaluated and compared between the two groups. The 40-keV Mono+ images in the LC-CM group showed comparable objective CNR (common carotid arteries: 83.7 ± 24.5 vs. 78.1 ± 23.2; internal carotid arteries: 82.2 ± 26.8 vs. 76.8 ± 24.1; middle cerebral arteries: 72.5 ± 24.6 vs. 70.6 ± 19.2; all p > 0.05) and subjective image scores (3.95 ± 0.19 vs. 3.83 ± 0.35; p > 0.05) compared with Mixed images in the HC-CM group. The Mono+ reconstruction technique could reduce the concentration of iodinated CM in the diagnosis of cerebral and cervical angiography. • Mono+ shows decreased noise and superior CNR compared with Mono. • The 40-keV Mono+ images show the highest CNR in the LC-CM group. • The Mono+ reconstruction technique could reduce the concentration of iodinated CM.

In light of the increasing number of radiologic interventions performed under general anesthesia, the effects of contrast media (CM) on circulation and organ perfusion are of paramount importance. The objectives of this study were to systematically quantify effects on blood pressure, heart rate, and kidney function following intravenous administration of nonionic CM with normal and low osmolality.In this controlled, double-blinded phase IV clinical trial, 40 consecutive patients were randomly assigned to receive repeated measures of either low-osmolar iopromide or iso-osmolar iodixanol. Normal saline solution (NSS) served as control. Blood pressure and heart rate were measured continuously from 1 minute before until 3 minutes after administration of CM and NSS. Urine output was recorded hourly.Administration of iopromide resulted in systemic hypotension lasting up to 300 seconds (105 ± 61 seconds) with the lowest mean arterial pressure of 39 mm Hg (56.7 ± 12.2 mm Hg). Iopromide caused a systolic/diastolic decrease of 31/26 mm Hg (P.001), significant increase in heart rate (P = .042), and significant diuresis with a 2-fold higher per-hour urine output (P = .010). Administration of iodixanol and NSS had no significant influence on blood pressure (P.640).Administration of low-osmolar iopromide was followed by a significant transient decrease in blood pressure and a rise in heart rate. Anesthetists and radiologists should be aware of these effects in patients in whom short episodes of disturbed tissue microcirculation may pose a clinical risk.

Summary Aims Contrast-induced nephropathy is a commonly encountered problem in clinical practice. The purpose of the study was to design and develop a novel contrast agent, which could be used to prevent contrast-induced nephropathy in the future. Methods In total, 20–220 nm magnetic nanoparticles were conjugated with iodixanol, and their radio-opacity and magnetic properties were assessed thereafter. Scanning electron microscopy pictures were acquired. Thereafter, the nanoparticles conjugate was tested in cell culture (HUVEC cells), and Quantibody® assay was studied after cell treatment in 1:5 dilutions for 48 h, compared with control. Results The conjugate preparation had an adequate radio-opacity. A 4 mm magnetic bubble was attached to a bar magnet and the properties were studied. The magnetic bubble maintained its structural integrity in all angles including antigravity position. Scanning electron microscopy showed magnetic nanoparticles in all pictures and the particles are of 100–400 nm agglomerates with primary particle sizes of roughly 20 nm. 1:5 diluted particles had no effect on secretion of IL-1a, IL-1b, IL-4, IL-10, IL-13 and TNFa. Particles increased secretion of IL-8 from 24 h and 48 h. Secretion of IFNg was also increased when particles were added to the cells as early as 1 h. Likewise, IL-6 was strongly secreted by HUVEC treated with particles from 24 h incubation time. In contrast, the secretion of MCP-1 was slightly reduced on HUVEC treated with particles. Conclusion There is potential for a novel iodixanol-magnetic nanoparticle conjugate to be used in cineradiography. Further investigations need to be performed to study its performance in vitro and in vivo.

Purpose To show that equal coronary lumen opacification can be achieved with iso- and low-osmolar contrast media when it is injected at the same iodine delivery rate with contemporary cardiac computed tomographic (CT) protocols and to investigate the cardiovascular effect of iso-osmolar contrast media and the image quality achieved. Materials and Methods Institutional review board approval and written informed consent were obtained for the Effect of Iso-osmolar Contrast Medium on Coronary Opacification and Heart Rhythm in Coronary CT Angiography, or IsoCOR, trial. Between November 2015 and August 2016, 306 patients (167 [55%] women) at least 18 years old (weight range, 50-125 kg), were prospectively randomized to receive iso-osmolar iodixanol 270 or low-osmolar iopromide 300 contrast media. All coronary segments were assessed for intraluminal opacification and image quality and were compared by using the Student t test. Heart rate, arrhythmia, patient discomfort, and adverse events also were monitored. Results Mean measured coronary attenuation values ± standard deviation were comparable between the iodixanol 270 and iopromide 300 contrast media groups (469 HU ± 167 vs 447 HU ± 166, respectively [P = .241]; 95% confidence interval: -15.1, 60.0), including those from subanalyses. Adjusted for the lower iodine concentration, the mean iodixanol 270 bolus was larger compared with that of iopromide 300 (76.8 mL ± 11.6 vs 69.7 mL ± 10.8, respectively; P.001). The higher injection rate was associated with higher pressure (777 kPa ± 308 vs 630 kPa ± 252, respectively; P.001). Although in the iodixanol 270 group patients experienced less heat discomfort (72% vs 86%, respectively; P.001), no differences in heart rate or rhythm were observed. Conclusion If injected at comparable iodine delivery rates, the iso-osmolar contrast medium iodixanol 270 is not inferior to low-osmolar contrast medium iopromide 300 for assessment of coronary opacification. Iodixanol 270 was associated with less heat discomfort, but did not affect heart rate differently compared with iopromide 300.