Impact of CT Injector Technology and Contrast Media Viscosity on Vascular Enhancement: Evaluation in a Circulation Phantom.

OBJECTIVE: To assess the impact of piston-based vs peristaltic injection system technology and contrast media viscosity on achievable iodine delivery rates (IDRs) and vascular enhancement in a pre-clinical study. METHODS: Four injectors were tested: MEDRAD® Centargo, MEDRAD® Stellant, CT Exprès®, and CT motion™ using five contrast media [iopromide (300 and 370 mgI ml-1), iodixanol 320 mgI ml-1, iohexol 350 mgI ml-1, iomeprol 400 mgI ml-1]. Three experiments were performed evaluating achievable IDR and corresponding enhancement in a circulation phantom. RESULTS: Experiment I: Centargo provided the highest achievable IDRs with all tested contrast media (p < 0.05). Iopromide 370 yielded the highest IDR with an 18G catheter (3.15 gI/s); iopromide 300 yielded the highest IDR with 20G (2.70 gI/s) and 22G (1.65 gI/s) catheters (p < 0.05).Experiment II: with higher achievable IDRs, piston-based injectors provided significantly higher peak vascular enhancement (up to 48% increase) than the peristaltic injectors with programmed IDRs from 1.8 to 2.4 gI/s (p < 0.05).Experiment III: with programmed IDRs (e.g. 1.5 gI/s) achievable by all injection systems, Centargo, with sharper measured bolus shape, provided significant increases in enhancement of 34-73 HU in the pulmonary artery with iopromide 370 (p < 0.05). CONCLUSION: The tested piston-based injection systems combined with low viscosity contrast media provide higher achievable IDRs and higher peak vascular enhancement than the tested peristaltic-based injectors. With equivalent IDRs, Centargo provides higher peak vascular enhancement due to improved bolus shape. ADVANCES IN KNOWLEDGE: This paper introduces a new parameter to compare expected performance among contrast media: the concentration/viscosity ratio. Additionally, it demonstrates previously unexplored impacts of bolus shape on vascular enhancement.

Cerebrospinal Fluid Characterization in Cynomolgus Monkeys, Beagle Dogs, and Göttingen Minipigs.

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.

Aging does not change the compressive stiffness of mandibular condylar cartilage in horses.

OBJECTIVE: Aging can cause an increase in the stiffness of hyaline cartilage as a consequence of increased protein crosslinks. By induction of crosslinking, a reduction in the diffusion of solutions into the hyaline cartilage has been observed. However, there is a lack of knowledge about the effects of aging on the biophysical and biochemical properties of the temporomandibular joint (TMJ) cartilage. Hence, the aim of this study was to examine the biophysical properties (thickness, stiffness, and diffusion) of the TMJ condylar cartilage of horses of different ages and their correlation with biochemical parameters. MATERIALS AND METHODS: We measured the compressive stiffness of the condyles, after which the diffusion of two contrast agents into cartilage was measured using Contrast Enhanced Computed Tomography technique. Furthermore, the content of water, collagen, GAG, and pentosidine was analyzed. RESULTS: Contrary to our expectations, the stiffness of the cartilage did not change with age (modulus remained around 0.7 MPa). The diffusion of the negatively charged contrast agent (Hexabrix) also did not alter. However, the diffusion of the uncharged contrast agent (Visipaque) decreased with aging. The flux was negatively correlated with the amount of collagen and crosslink level which increased with aging. Pentosidine, collagen, and GAG were positively correlated with age whereas thickness and water content showed negative correlations. CONCLUSION: Our data demonstrated that aging was not necessarily reflected in the biophysical properties of TMJ condylar cartilage. The combination of the changes happening due to aging resulted in different diffusive properties, depending on the nature of the solution.

Iso-Osmolar Iodixanol Induces Less Increase in Circulating Endothelial Microparticles In Vivo and Less Endothelial Apoptosis In Vitro Compared with Low-Osmolar Iohexol.

Background and Aims: There is no consensus on whether iodixanol is superior to iohexol. This study aimed to compare the effects of iodixanol and iohexol on circulating endothelial microparticles (EMPs) in stable coronary artery disease (CAD) patients with diabetes mellitus (DM), and also their cytotoxic effects on human umbilical vein endothelial cells (HUVECs) in vitro. Methods: 100 CAD patients with DM were randomly assigned to receive iso-osmolar contrast medium iodixanol (group I) or low-osmolar iohexol (group II) during coronary angioplasty. An additional 49 CAD patients without DM receiving iohexol were recruited as group III. Circulating CD31+/CD41a- EMPs, CD62E+ EMPs, and CD31+/CD41a+ platelet microparticles (PMPs) were determined by flow cytometry. In vitro, the cytotoxic effects of iodixanol and iohexol on HUVECs were determined. Results: Circulating CD31+/CD41a- EMPs and PMPs were significantly increased after angioplasty in all 3 groups, while CD62E+ EMPs significantly decreased in group I. CD31+/CD41a- EMPs and PMPs were significantly higher in group II than group I or III. In vitro, both contrast media induced EMP release and inhibited the viability and induced apoptosis of HUVECs, as well as increasing Bax and cleaved caspase-3 and decreasing Bcl-2. The above effects were less evident in iodixanol than in iohexol. Conclusions: Compared with iohexol, iodixanol induces less release of EMPs in both CAD patients with DM during angioplasty and in vitro HUVEC culture, which is associated with less pronounced proapoptotic effects of iodixanol on HUVECs. Clinical Study Registration Number: This study is registered with ChiCTR-TRC-14005183.

Assessment of iodine uptake by pancreatic cancer following chemotherapy using dual-energy CT.

Pancreatic cancer remains a major health problem, and only less than 20% of patients have resectable disease at the time of initial diagnosis. Systemic chemotherapy is often used in the patients with borderline resectable, locally advanced unresectable disease and metastatic disease. CT is often used to assess for therapeutic response; however, conventional imaging including CT may not correctly reflect treatment response after chemotherapy. Dual-energy (DE) CT can acquire datasets at two different photon spectra in a single CT acquisition, and permits separating materials and extract iodine by applying a material decomposition algorithm. Quantitative iodine mapping may have an added value over conventional CT imaging for monitoring the treatment effects in patients with pancreatic cancer and potentially serve as a unique biomarker for treatment response. In this pictorial essay, we will review the technique for iodine quantification of pancreatic cancer by DECT and discuss our observations of iodine quantification at baseline and after systemic chemotherapy with conventional cytotoxic agents, and illustrate example cases.

Comparison of virtual unenhanced CT images of the abdomen under different iodine flow rates.

OBJECTIVE: To assess the effect of varying iodine flow rate (IFR) and iodine concentration on the quality of virtual unenhanced (VUE) images of the abdomen obtained with dual-energy CT. METHODS: 94 subjects underwent unenhanced and triphasic contrast-enhanced CT scan of the abdomen, including arterial phase, portal venous phase, and delayed phase using dual-energy CT. Patients were randomized into 4 groups with different IFRs or iodine concentrations. VUE images were generated at 70 keV. The CT values, image noise, SNR and CNR of aorta, portal vein, liver, liver lesion, pancreatic parenchyma, spleen, erector spinae, and retroperitoneal fat were recorded. Dose-length product and effective dose for an examination with and without plain phase scan were calculated to assess the potential dose savings. Two radiologists independently assessed subjective image quality using a five-point scale. The Kolmogorov-Smirnov test was used first to test for normal distribution. Where data conformed to a normal distribution, analysis of variance was used to compare mean HU values, image noise, SNRs and CNRs for the 4 image sets. Where data distribution was not normal, a nonparametric test (Kruskal-Wallis test followed by stepwise step-down comparisons) was used. The significance level for all tests was 0.01 (two-sided) to allow for type 2 errors due to multiple testing. RESULTS: The CT numbers (HU) of VUE images showed no significant differences between the 4 groups (p > 0.05) or between different phases within the same group (p > 0.05). VUE images had equal or higher SNR and CNR than true unenhanced images. VUE images received equal or lower subjective image quality scores than unenhanced images but were of acceptable quality for diagnostic use. Calculated dose-length product and estimated dose showed that the use of VUE images in place of unenhanced images would be associated with a dose saving of 25%. CONCLUSIONS: VUE images can replace conventional unenhanced images. VUE images are not affected by varying iodine flow rates and iodine concentrations, and diagnostic examinations could be acquired with a potential dose saving of 25%.

Bioresponsive and fluorescent hyaluronic acid-iodixanol nanogels for targeted X-ray computed tomography imaging and chemotherapy of breast tumors.

Nanotheranostics is a rapidly growing field combining disease diagnosis and therapy, which ultimately may add in the development of 'personalized medicine'. Here, we designed and developed bioresponsive and fluorescent hyaluronic acid-iodixanol nanogels (HAI-NGs) for targeted X-ray computed tomography (CT) imaging and chemotherapy of MCF-7 human breast tumors. HAI-NGs were obtained with a small size of ca. 90nm, bright green fluoresence and high serum stability from hyaluronic acid-cystamine-tetrazole and reductively degradable polyiodixanol-methacrylate via nanoprecipitation and a photo-click crosslinking reaction. Notably, paclitaxel (PTX)-loaded HAI-NGs showed a fast glutathione-responsive drug release. Confocal microscopy displayed efficient uptake of HAI-NGs by CD44 overexpressing MCF-7 cells via a receptor-mediated mechanism. MTT assays revealed that HAI-NGs were nontoxic to MCF-7 cells even at a high concentration of 1mg/mL whereas PTX-loaded HAI-NGs exhibited strong inhibition of MCF-7 cells. The in vivo pharmcokinetics, near-infrared imaging and biodistribution studies revealed that HAI-NGs significantly prolonged the blood circulation time and enhanced tumor accumulation of PTX. Interestingly, significantly enhanced CT imaging was observed for MCF-7 breast tumors in nude mice via either intratumoral or intravenous injection of HAI-NGs as compared to iodixanol. HAI-NGs fluoresence was distributed thoughout the whole tumor indicating deep tumor penetration. PTX-loaded HAI-NGs showed effective suppression of tumor growth with little systemic toxicity. HAI-NGs appear as a "smart" theranostic nanoplatform for the treatment of CD44 positive tumors.

A non-invasive cardiac output measurement as an alternative to the test bolus technique during CT angiography.

AIM: To investigate the association between a non-invasive cardiac output (CO) measurement and the scan delay, as derived from a test bolus injection protocol. The secondary objective was to determine which factors affect the relationship between the CO and scan delay. MATERIALS AND METHODS: Fifty-five patients referred for a contrast-enhanced (thorax-)abdomen CT examination were included in this feasibility study. A test bolus examination was performed prior to the abdominal CT. During the test bolus injection, the CO of the patient was measured using a non-invasive finger-cuff measurement. Associations were analysed using linear regression analyses. Age, gender, height, weight, and blood pressure were included as potential confounders. RESULTS: Linear regression analysis showed a negative and significant association between CO and delay. The regression formula was as follows: scan delay (seconds) = 26.8-1.6 CO (l/min), with a 95% CI between -2.3 and -1.0 (p<0.001). Weight appeared to be a confounder in this relation, and gender and blood pressure were effect modifiers. There was no interaction between scan delay and age, height and weight. CONCLUSIONS: There is a negative and significant association between the non-invasive CO measurement and the CT scan delay; however, to validate these findings a larger cohort study is needed to investigate whether the non-invasively determined scan delay is as accurate as the use of a test bolus.

Multidetector CT of pancreatic ductal adenocarcinoma: Effect of tube voltage and iodine load on tumour conspicuity and image quality.

OBJECTIVES: To compare a low-tube-voltage with or without high-iodine-load multidetector CT (MDCT) protocol with a normal-tube-voltage, normal-iodine-load (standard) protocol in patients with pancreatic ductal adenocarcinoma (PDAC) with respect to tumour conspicuity and image quality. METHODS: Thirty consecutive patients (mean age: 66 years, men/women: 14/16) preoperatively underwent triple-phase 64-channel MDCT examinations twice according to: (i) 120-kV standard protocol (PS; 0.75 g iodine (I)/kg body weight, n = 30) and (ii) 80-kV protocol A (PA; 0.75 g I/kg, n = 14) or protocol B (PB; 1 g I/kg, n = 16). Two independent readers evaluated tumour delineation and image quality blindly for all protocols. A third reader estimated the pancreas-to-tumour contrast-to-noise ratio (CNR). Statistical analysis was performed with the Chi-square test. RESULTS: Tumour delineation was significantly better in PB and PA compared with PS (P = 0.02). The evaluation of image quality was similar for the three protocols (all, P > 0.05). The highest CNR was observed with PB and was significantly better compared to PA (P = 0.02) and PS (P = 0.0002). CONCLUSION: In patients with PDAC, a low-tube-voltage, high-iodine-load protocol improves tumour delineation and CNR leading to higher tumour conspicuity compared to standard protocol MDCT. KEY POINTS: • Low-tube-voltage high-iodine-load MDCT improves pancreatic cancer conspicuity compared to a standard protocol. • The pancreas-to-tumour attenuation difference increases significantly by reducing the tube voltage. • The radiation exposure dose decreases by reducing the tube voltage.

Exponentially Decelerated Contrast Media Injection Rate Combined With a Novel Patient-Specific Contrast Formula Reduces Contrast Volume Administration and Radiation Dose During Computed Tomography Pulmonary Angiography.

CLINICAL RELEVANCE: Matching contrast injection timing with vessel dynamics significantly improves vessel opacification and reduces contrast dose in the assessment of pulmonary embolism during computed tomography (CT) pulmonary angiography. PURPOSE: The aim of this study was to investigate opacification of the pulmonary vasculature (PV) during CT pulmonary angiography using a patient-specific contrast formula (PSCF) and exponentially decelerated contrast media (EDCM) injection rate. MATERIALS AND METHODS: Institutional review board approved this retrospective study. Computed tomography pulmonary angiography was performed on 200 patients with suspected pulmonary embolism using a 64-channel CT scanner. Patient demographics were equally distributed. Patients were randomly assigned to 2 equal protocol groups: protocol A used a PSCF, and protocol B involved the use of a PSCF combined with EDCM. The mean cross-sectional opacification profile of 8 central and 11 peripheral PVs were measured for each patient, and arteriovenous contrast ratio was calculated. Protocols were compared using Mann-Whitney U nonparametric statistics. Jackknife alternative free-response receiver operating characteristic analyses were used to assess diagnostic efficacy. Interobserver variations were investigated using kappa methods. RESULTS: A number of pulmonary arteries demonstrated increases in opacification (P < 0.02) for protocol B compared with A, whereas opacification in all veins was reduced in protocol B (P < 0.03). Subsequently, increased arteriovenous contrast ratio in protocol B compared with A was observed at all anatomic locations (P < 0.0002). An increase in jackknife alternative free-response receiver operating characteristic figure of merit (P < 0.0002) and interobserver variation was observed with protocol B compared with protocol A (κ = 0.3-0.73). Mean contrast volume was reduced in protocol B (29 [4] mL) compared with protocol A (33 [9] mL). Mean effective radiation dose in protocol B (1.2 [0.4] mSv) was reduced by 14% compared with protocol A (1.4 [0.6] mSv). CONCLUSIONS: Significant improvements in visualization of the PV can be achieved with a low contrast volume using an EDCM and PSCF. The reduced risk of cancer induction is highlighted.

Relationship of glomerular filtration rate based on serum iodixanol clearance to IRIS staging in cats with chronic kidney disease.

We examined the correlation between the glomerular filtration rate (GFR) estimated from an equation based on the serum iodixanol clearance technique and International Renal Interest Society (IRIS) stages of chronic kidney disease (CKD) in cats. The equation included the injection dose, sampling time, serum concentration and estimated volume of distribution (Vd) of the isotonic, nonionic, contrast medium iodixanol as a test tracer. The percent changes in the median basal GFR values calculated from the equation in CKD cats resembled those of IRIS stages 1-3. These data validate the association between the GFR derived from the simplified equation and IRIS stages based on the serum creatinine concentration in cats with CKD. They describe the GFR ranges determined using single-sample iodixanol clearance for healthy cats and cats with various IRIS stages of CKD.

Iodine Distribution Map in Dual-Energy Computed Tomography Pulmonary Artery Imaging with Rapid kVp Switching for the Diagnostic Analysis and Quantitative Evaluation of Acute Pulmonary Embolism.

RATIONALE AND OBJECTIVES: To assess the diagnostic value of dual-energy (DE) computed tomography pulmonary angiography (CTPA) for acute pulmonary embolism (PE) using a helical DE scan mode with rapid kVp switching. MATERIALS AND METHODS: Seventy-six patients with suspected acute PE underwent DE CTPA. Two readers independently assessed and measured the iodine maps. CTPA images were assessed for the presence, location, and degree of PE as the standard of reference. Iodine maps were used to identify the perfusion defect (PD), and the diagnostic accuracy of iodine maps was calculated. The iodine concentrations of PDs and normal lung parenchyma were also measured and compared. RESULTS: A per-patient analysis showed the 84.6% sensitivity and 96.0% specificity of iodine map for PE, and on per-segment analysis, the sensitivity and specificity for PE were 82.9% and 99.6%, respectively. Intraobserver and interobserver variability correlations were excellent, with k values from 0.806 to 1.000. Quantitative analysis showed there was a significant difference for iodine concentration between circumscribed/patchy PDs or wedge-shaped PDs consistent with PE and normal lung parenchyma (P < .05). The intraobserver reliability of reader 1 was from 0.928 to 0.997, and reader 2 was from 0.912 to 0.995. And, the interobserver reliability between two readers was from 0.967 to 0.999. CONCLUSIONS: CTPA based on DE scanning with rapid kVp switching can provide both morphologic analysis and quantitative evaluation of PD related to acute PE in addition to standard CTPA data. Quantification of iodine concentration may be helpful for identifying the presence or absence of PE.

The use of iodinated contrast media in patients with end-stage renal disease.

Iodinated contrast agents are well tolerated in ESRD patients. Certain types of ICM, i.e., LOCM and the nonionic agents are associated with better safety profiles. Current available evidence, although not optimal, does not support the need for additional hemodialysis for ICM removal to preserve residual renal function or to treat other potential toxicities of ICM. However, limiting exposure to ICM is a prudent measure in ESRD patients given ICM's potential toxicity; close monitoring of patients with poor cardiac function is also recommended in subjects receiving higher doses of ICM, especially those receiving HOCM.

Use of time attenuation curves to determine steady-state characteristics before C-arm CT measurement of cerebral blood volume.

INTRODUCTION: Cerebral blood volume (CBV) measurement by flat panel detector CT (FPCT) in the angiography suite seems to be a promising tool for patient management during endovascular therapies. A steady state of contrast agent distribution is mandatory during acquisition for accurate FPCT CBV assessment. To the best of our knowledge, this was the first time that steady-state parameters were studied in clinical practice. METHODS: Before the CBV study, test injections were performed and analyzed to determine a customized acquisition delay from injection for each patient. Injection protocol consisted in the administration of 72 mL of contrast agent material at the injection rate of 4.0 mL/s followed by a saline flush bolus at the same injection rate. Peripheral or central venous accesses were used depending on their availability. Twenty-four patients were treated for different types of neurovascular diseases. Maximal attenuation, steady-state length, and steady-state delay from injection were derived from the test injections' time attenuation curves. RESULTS: With a 15 % threshold from maximum attenuation values, average steady-state duration was less than 10 s. Maximum average steady-state duration with minimal delay variation was obtained with central injection protocols. CONCLUSION: With clinically acceptable contrast agent volumes, steady state is a brief condition; thus, fast rotation speed acquisitions are needed. The use of central injections decreases the variability of steady-state's delay from injection. Further studies are needed to optimize and standardize injection protocols to allow a larger diffusion of the FPCT CBV measurement during endovascular treatments.

How influential is the duration of contrast material bolus injection in perfusion CT? evaluation in a swine model.

PURPOSE: To analyze the effect of the duration of contrast material bolus injection on perfusion values in a swine model by using the maximum slope method. MATERIALS AND METHODS: This study was approved by the institutional animal care committee. Twenty pigs (weight range, 63-77 kg) underwent dynamic volume computed tomography (CT) of the kidneys during suspended respiration. Before the CT examination, a miniature cuff-shaped ultrasonographic flow probe encircling the right renal artery was surgically implanted in each pig to obtain true perfusion values. Two sequential perfusion CT series were performed in 30 seconds, each comprising 30 volumes with identical parameters (100 kV, 200 mAs, 0.5 sec rotation time). The duration of contrast material bolus (0.5 mL/kg of body weight) was 3.8 seconds in the first series (short bolus series) and 11.5 seconds in the second series (long bolus series), and the injection flow rate was adapted accordingly. In each pig, cortical kidney volume was determined by using the volume with the highest cortical enhancement. CT perfusion values were calculated for both series by using the maximum slope method and were statistically compared and correlated with the true perfusion values from the flow probe by using linear regression analysis. RESULTS: Mean true perfusion and CT perfusion values (in minutes(-1)) for the short bolus series were 1.95 and 2.03, respectively (P = .22), and for the long bolus series, they were 2.02 and 1.92, respectively (P = .12). CT perfusion showed very good correlation with true perfusion in both the short (slope, 1.01; 95% confidence interval: 0.91, 1.11) and long (slope, 0.92; 95% confidence interval: 0.78, 1.04) series. On the basis of the regression analysis, CT perfusion values in the short bolus series were overestimated by 1% and those in the long bolus series were underestimated by 8%. CONCLUSION: Duration of contrast material bolus injection does not influence CT perfusion values substantially. The longer, clinically preferred intravenous injection scheme is sufficiently accurate for CT perfusion.

Technical note: Use of a simplified equation for estimating glomerular filtration rate in beef cattle.

This study was performed to clarify whether a formula (Holstein equation) based on a single blood sample and the isotonic, nonionic, iodine contrast medium iodixanol in Holstein dairy cows can apply to the estimation of glomerular filtration rate (GFR) for beef cattle. To verify the application of iodixanol in beef cattle, instead of the standard tracer inulin, both agents were coadministered as a bolus intravenous injection to identical animals at doses of 10 mg of I/kg of BW and 30 mg/kg. Blood was collected 30, 60, 90, and 120 min after the injection, and the GFR was determined by the conventional multisample strategies. The GFR values from iodixanol were well consistent with those from inulin, and no effects of BW, age, or parity on GFR estimates were noted. However, the GFR in cattle weighing less than 300 kg, aged<1 yr old, largely fluctuated, presumably due to the rapid ruminal growth and dynamic changes in renal function at young adult ages. Using clinically healthy cattle and those with renal failure, the GFR values estimated from the Holstein equation were in good agreement with those by the multisample method using iodixanol (r=0.89, P=0.01). The results indicate that the simplified Holstein equation using iodixanol can be used for estimating the GFR of beef cattle in the same dose regimen as Holstein dairy cows, and provides a practical and ethical alternative.

Noninvasive technique for monitoring drug transport through the murine cochlea using micro-computed tomography.

Local delivery of drugs to the inner ear has the potential to treat inner ear disorders including permanent hearing loss or deafness. Current mathematical models describing the pharmacokinetics of drug delivery to the inner ear have been based on large rodent studies with invasive measurements of concentration at few locations within the cochlea. Hence, estimates of clearance and diffusion parameters are based on fitting measured data with limited spatial resolution to a model. To overcome these limitations, we developed a noninvasive imaging technique to monitor and characterize drug delivery inside the mouse cochlea using micro-computed tomography (µCT). To increase the measurement accuracy, we performed a subject-atlas image registration to exploit the information readily available in the atlas image of the mouse cochlea and pass segmentation or labeling information from the atlas to our µCT scans. The approach presented here has the potential to quantify concentrations at any point along fluid-filled scalae of the inner ear. This may permit determination of spatially dependent diffusion and clearance parameters for enhanced models.

Assessment of the tracer delay effect in whole-brain computed tomography perfusion: results in patients without known neuroanatomic abnormalities.

OBJECTIVE: Whole-brain computed tomography perfusion (CTP) data sets generated by tracer delay-insensitive singular value decomposition plus (SVD+) and standard singular value decomposition (sSVD) deconvolution algorithms were evaluated to quantify relatedness and discrepancies in CTP results. METHODS: Twenty females with symmetrical hemispheric CTP maps indicative of brain tissue without apparent abnormalities were studied. Tissue-specific CTP values were analyzed. RESULTS: Standard SVD values were higher than SVD+ for cerebral blood flow. Other CTP values had minimal differences across brain regions. All simple linear regression models were statistically significant (P < 0.05) except for cerebral blood flow in white matter (P = 0.06). Cerebral blood volume had a good model fit, and mean transit time, a poor fit. CONCLUSIONS: Corresponding fitted CTP values for sSVD and SVD+ based on regression equations for brain-tissue types are presented. Additional research is required to compare SVD+ and sSVD in disease states when significant hemodynamic brain alterations are present.

Iodinated α-tocopherol nano-emulsions as non-toxic contrast agents for preclinical X-ray imaging.

Micro-computed tomography (micro-CT) is an emerging imaging modality, due to the low cost of the imagers as well as their efficiency in establishing high-resolution (1-100 µm) three-dimensional images of small laboratory animals and facilitating rapid, structural and functional in vivo visualization. However use of a contrast agent is absolutely necessary when imaging soft tissues. The main limitation of micro-CT is the low efficiency and toxicity of the commercially available blood pool contrast agents. This study proposes new, efficient and non-toxic contrast agents for micro-CT imaging. This formulation consists of iodinated vitamin E (α-tocopheryl 2,3,5-triiodobenzoate) as an oily phase, formulated as liquid nano-emulsion droplets (by low-energy nano-emulsification), surrounded by a hairy PEG layer to confer stealth properties. The originality and strength of these new contrast agents lie not only in their outstanding contrasting properties, biocompatibility and low toxicity, but also in the simplicity of their fabrication: one-step synthesis of highly iodinated oil (iodine constitutes 41.7% of the oil molecule weight) and its spontaneous emulsification. After i.v. administration in mice (8.5% of blood volume), the product shows stealth properties towards the immune system and thus acts as an efficient blood pool contrast agent (t(1/2) = 9.0 h), exhibiting blood clearance following mono-exponential decay. A gradual accumulation predominantly due to hepatocyte uptake is observed and measured in the liver, establishing a strong hepatic contrast, persistent for more than four months. To summarize, in the current range of available or developed contrast agents for preclinical X-ray imaging, this agent appears to be one of the most efficient.