Impact of various iodine concentrations of iohexol and iodixanol contrast media on image reconstruction techniques in a vascular-specific contrast media phantom: quantitative and qualitative image quality assessment.

PURPOSE: The aim of our study is to investigate the impact of iodine quantification on image reconstruction when employing a vascular-specific contrast media phantom with varying iodine concentrations. MATERIALS AND METHODS: A 30-cm phantom simulating arterial and venous blood vessel diameters was manufactured. Small (9 mm) and medium (12 mm) cylinders contained iodine concentrations from 10 to 100% while large (21 mm) cylinders were in quartiles from 25 to 100% diluted in blood equivalent medium. Each phantom was filled with either iohexol 350 mgI/mL (Group A) or iodixanol 320 mgI/mL (Group B) and then scanned separately. For each group, tube potential (80-140 kVp) and current (50-400 mAs) were changed and all image series were reconstructed with filtered back projection (FBP), hybrid-based iterative reconstruction (HBIR) and model-based iterative reconstruction (MBIR). Mean opacification was measured in all groups. All data were compared employing an independent t test and Pearson's correlation. Visual grading characteristic (VGC) and Cohens' kappa analyses were performed. RESULTS: At 80 kVp, mean opacification using HBIR was significantly higher in Group B (2165 ± 1108 HU) than in Group A (2040 ± 1036 HU) (p < 0.009). At 140 kVp, MBIR and HBIR were greater in Group A (1704 ± 1033 HU and 1685 ± 1023 HU) versus Group B (1567 ± 1036 HU and 1567 ± 1034 HU) (p < 0.022). CNR using FBP, HBIR and MBIR was higher in Group B (46 ± 42 HU, 70 ± 163 HU and 83 ± 74 HU, respectively) than in Group A (43 ± 39 HU, 174 ± 130 HU and 80 ± 65 HU, respectively) (p < 0.0001-0.035). Qualitative image analysis demonstrated no difference in Cohen's kappa analysis. VGC was higher in Group A at all image reconstruction groups. CONCLUSION: Iohexol outperforms iodixanol in observer performance when assessing image reconstruction techniques and iodine concentrations in a vascular-specific contrast media phantom.

A comparison of AAV-vector production methods for gene therapy and preclinical assessment.

Adeno Associated Virus (AAV)-mediated gene expression in the brain is widely applied in the preclinical setting to investigate the therapeutic potential of specific molecular targets, characterize various cellular functions, and model central nervous system (CNS) diseases. In therapeutic applications in the clinical setting, gene therapy offers several advantages over traditional pharmacological based therapies, including the ability to directly manipulate disease mechanisms, selectively target disease-afflicted regions, and achieve long-term therapeutic protein expression in the absence of repeated administration of pharmacological agents. Next to the gold-standard iodixanol-based AAV vector production, we recently published a protocol for AAV production based on chloroform-precipitation, which allows for fast in-house production of small quantities of AAV vector without the need for specialized equipment. To validate our recent protocol, we present here a direct side-by-side comparison between vectors produced with either method in a series of in vitro and in vivo assays with a focus on transgene expression, cell loss, and neuroinflammatory responses in the brain. We do not find differences in transduction efficiency nor in any other parameter in our in vivo and in vitro panel of assessment. These results suggest that our novel protocol enables most standardly equipped laboratories to produce small batches of high quality and high titer AAV vectors for their experimental needs.

In Vitro and In Vivo Assessment of Nonionic Iodinated Radiographic Molecules as Chemical Exchange Saturation Transfer Magnetic Resonance Imaging Tumor Perfusion Agents.

OBJECTIVES: The aim of this study was to evaluate 4 nonionic x-ray iodinated contrast agents (CAs), commonly used in radiographic procedures, as novel chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) agents by assessing their in vitro exchange properties and preliminary in vivo use as tumor enhancing agents. MATERIALS AND METHODS: The CEST properties, as function of pH (range, 5.5-7.9) and of radio frequency conditions (irradiation field strength range of 1-9 µT and time of 1-9 seconds), have been determined at 7 T and 310 K for 4 x-ray CAs commonly used in clinical settings, namely, iomeprol, iohexol, ioversol, and iodixanol. Their in vivo properties have been investigated upon intravenous injection in a murine HER2+ breast tumor model (n = 4 mice for each CA) using both computed tomography (CT) and MRI modalities. RESULTS: The prototropic exchange rates measured for the 4 investigated iodinated molecules showed strong pH dependence with base catalyzed exchange rate that was faster for monomeric compounds (20-4000 Hz in the pH range of 5.5-7.9). Computed tomography quantification showed marked (up to 2 mg I/mL concentration) and prolonged accumulation (up to 30 minutes postinjection) inside tumor regions. Among the 4 agents we tested, iohexol and ioversol display good CEST contrast properties at 7 T, and in vivo results confirmed strong and prolonged contrast enhancement of the tumors, with elevated extravasation fractions (74%-91%). A strong and significant correlation was found between CT and CEST-MRI tumor-enhanced images (R = 0.70, P < 0.01). CONCLUSIONS: The obtained results demonstrate that iohexol and ioversol, 2 commonly used radiographic compounds, can be used as MRI perfusion agents, particularly useful when serial images acquisitions are needed to complement CT information.

Cost-effectiveness of iso- versus low-osmolality contrast media in outpatients with high risk of contrast medium-induced nephropathy.

INTRODUCTION: Contrast media can cause acute renal failure by direct toxic effects on the tubular cells and kidney ischemia. Diabetics and hospitalized patients have a greater risk of developing contrast-induced nephropathy than the general population. OBJECTIVE: The cost effectiveness of iso and low-osmolality contrast media was assessed in high risk outpatients. MATERIALS AND METHODS: The analysis was based on a systematic literature review comparing the nephrotoxic effects of iso- to low-osmolality contrast media. Only direct costs were considered; these were obtained from the official tariff manual. Incremental cost-effectiveness ratios, efficiency curves and acceptability curves were calculated. Univariate sensitivity analyses were performed for costs and effects, as well as probabilistic analyses. Zero and 3% discounts were applied to results. The cost-effectiveness threshold was equal to the per capita GDP per life-year gained. RESULTS: Alternatives with Iopamidol and Iodixanol are preferable to the others, because both reduce risk of contrast-induced nephropathy and are less costly. The incremental cost-effectiveness of the Iodixanol alternative compared to the Iopamidol alternative is US$ 14,660 per additional life year gained; this is more than twice the threshold. CONCLUSION: The low-osmolality contrast medium, Iopamidol, appears to be cost-effective when compared with Iohexol or other low-osmolality contrast media (Iopromide, Iobitridol, Iomeprol, Iopentol and Ioxilan) in contrast-induced nephropathy, high-risk outpatients. The choice of the iso-osmolality contrast medium, Iodixanol, depends on its cost per vial and on the willingness to pay.

Cost-effectiveness of iso- versus low-osmolality contrast media in outpatients with high risk of contrast medium-induced nephropathy / Costo-efectividad de medios de contraste isoosmolales e hiposmolales en pacientes con alto riesgo de nefropatía inducida por medio de contraste

Introduction. Contrast media can cause acute renal failure by direct toxic effects on the tubular cells and kidney ischemia. Diabetics and hospitalized patients have a greater risk of developing contrast-induced nephropathy than the general population. Objective. The cost effectiveness of iso and low-osmolality contrast media was assessed in high risk outpatients. Materials and methods. The analysis was based on a systematic literature review comparing the nephrotoxic effects of iso- to low-osmolality contrast media. Only direct costs were considered; these were obtained from the official tariff manual. Incremental cost-effectiveness ratios, efficiency curves and acceptability curves were calculated. Univariate sensitivity analyses were performed for costs and effects, as well as probabilistic analyses. Zero and 3% discounts were applied to results. The cost-effectiveness threshold was equal to the per capita GDP per life-year gained. Results. Alternatives with Iopamidol and Iodixanol are preferable to the others, because both reduce risk of contrast-induced nephropathy and are less costly. The incremental cost-effectiveness of the Iodixanol alternative compared to the Iopamidol alternative is US$ 14,660 per additional life year gained; this is more than twice the threshold. Conclusion. The low-osmolality contrast medium, Iopamidol, appears to be cost-effective when compared with Iohexol or other low-osmolality contrast media (Iopromide, Iobitridol, Iomeprol, Iopentol and Ioxilan) in contrast-induced nephropathy, high-risk outpatients. The choice of the iso-osmolality contrast medium, Iodixanol, depends on its cost per vial and on the willingness to pay.

Introducción. Los medios de contraste pueden provocar falla renal aguda por toxicidad directa sobre las células tubulares e isquemia medular renal. Los pacientes diabéticos y los hospitalizados presentan mayor riesgo de desarrollar nefropatía inducida por medios de contraste que la población general. Objetivo. Establecer el costo-efectividad de los medios de contraste isosmolales e hiposmolales en pacientes con alto riesgo. Materiales and métodos. El análisis se basó en una revisión sistemática de la literatura científica, comparando los efectos nefrotóxicos de los medios isosmolales e hipoosmolales. Se consideraron sólo los costos directos, obtenidos del manual tarifario. Se calcularon las tasas del incremento del costo-efectividad, las curvas de eficiencia y de aceptabilidad. Se hicieron análisis univariados de sensibilidad para costos y efectos, así como probabilísticos. Se aplicaron tasas de descuento de 0 y 3 % a los resultados. Se usó como umbral de costo-efectividad por año de vida ganado, el producto interno bruto per cápita. Resultados. Las alternativas con Iopamidol y Iodixanol dominan a las demás porque reducen el riesgo de nefropatía inducida por contraste a un menor costo. La razón del incremento del costo-efectividad del iodixanol comparado con el iopamidol es de US$ 14.660 por año de vida ganado que más que duplica el umbral. Conclusión. El medio de baja osmolalidad, iopamidol, parece ser costo-efectivo comparado con iohexol u otros medios hiposmolares (iopromide, iobitridol, iomeprol, iopentol y ioxilan), en pacientes con alto riesgo de nefropatía inducida por contraste. La elección del medio hiposmolar, depende de la disponibilidad a pagar o del costo por ampolleta.

Histopaque provides optimal mouse islet purification kinetics: comparison study with Ficoll, iodixanol and dextran.

Islet transplantation has become a very promising treatment for type 1 diabetes. To facilitate further clinical improvements in this exciting field, rodent islets are used to evaluate new strategies and modifications. One method to purify islets is on a density gradient, although the optimal gradient component can be debated. N=6 separate mouse islet isolations were used and the resulting islets were separated and purified on either a Ficoll, Histopaque, Dextran or Iodixanol gradient. Islets were assessed for recovery, viability, purity and in vitro functionality. Aliquots were transplanted into diabetic mice to assess in vivo functionality and survival. There was no difference in the number of islets recovered across groups nor in the size of recovered islets. Use of a Ficoll or Histopaque gradient led to the most pure and viable islets in comparison to Dextran and Iodixanol. Functionally, islets isolated on a Ficoll gradient had the highest glucose-stimulated insulin release in vitro while performing equally to Histopaque and Dextran gradients in vivo. Using a Ficoll gradient, however, comes at a higher monetary cost. We recommend using a Histopaque gradient, which led to the isolation of viable and functional islets with a reduced cost as compared to a Ficoll gradient.

Development and evaluation of a liquid chromatography-mass spectrometry assay and its application for the assessment of renal function.

In the present study we evaluated two commonly used iodinated contrast agents, iohexol and iodixanol, as potential markers of impaired renal function. A reversed phase LC-MS method has been developed in order to separate and quantify the two substances. The assay was linear between 0.02 and 9.7 micromol/L for iohexol and between 0.4 and 49.3 micromol/L for iodixanol (r(2) > 0.998). The recovery during sample preparation ranged from 89.1 to 112.4%. The intra- and inter-assay RSD values were 3.06-13.6% for iohexol and 4.32-12.7% for iodixanol. The validated method was subsequently applied to 17 patients scheduled for angiographic procedure displaying normal and impaired renal function. A mixture of iohexol and iodixanol was intra-arterially injected and their corresponding plasma levels were determined periodically over a 24h period following administration. The elimination of both contrast agents followed by the LC-MS approach allowed us to discriminate between patients with normal and impaired renal function at 4, 8 and 24h after administration. Our preliminary results support the predictive value of iohexol and/or iodixanol clearance in a clinical environment to screen and identify patients at risk of developing CIN.