Contrast Concentrations Research Articles

Stability of MRI contrast agents in high-energy radiation of a 1.5T MR-Linac

BackgroundGadolinium-based contrast is often used when acquiring MR images for radiation therapy planning for better target delineation. In some situations, patients may still have residual MRI contrast agents in their tissue while being treated with high-energy radiation. This is especially true when MRI contrast agents are administered during adaptive treatment replanning for patients treated on MR-Linac systems. PurposeThe purpose of this study was to analyze the molecular stability of MRI contrast agents when exposed to high energy photons and the associated secondary electrons in a 1.5T MR-Linac system. This was the first step in assessing the safety of administering MRI contrast agents throughout the course of treatment. Materials and methodsTwo common MRI contrast agents were irradiated with 7 MV photons to clinical dose levels. The irradiated samples were analyzed using liquid chromatography-high resolution mass spectrometry to detect degradation products or conformational alterations created by irradiation with high energy photons and associated secondary electrons. ResultsNo significant change in chemical composition or displacement of gadolinium ions from their chelates was discovered in samples irradiated with 7 MV photons at relevant clinical doses in a 1.5T MR-Linac. Additionally, no significant correlation between concentrations of irradiated MRI contrast agents and radiation dose was observed. ConclusionThe chemical composition stability of the irradiated contrast agents is promising for future use throughout the course of patient treatment. However, in vivo studies are needed to confirm that unexpected metabolites are not created in biological milieus.

MO336RENAL CONTRAST-ENHANCED ULTRASOUND (CEUS) TO EVALUATE EARLY AND CHRONIC MODIFICATIONS OF RENAL PERFUSION AND TO PREDICT RENAL DYSFUNCTION AFTER RENAL ISCHEMIA-REPERFUSION IN MICE

Abstract Background and Aims Renal ischemia-reperfusion can lead to acute kidney injury (AKI), increasing the risk of developing chronic kidney disease (CKD) through inflammation and vascular lesions. Serum urea or creatinine level routinely used as diagnostic indices of renal function are always delayed from the onset of the disease. Therefore, we currently lack reliable markers to early detect AKI, especially in animals. We aimed to show that non-invasive renal contrast-enhanced ultrasound (CEUS) could be a reliable tool to assess early and chronic changes of renal perfusion after renal ischemia-reperfusion. Method Male C57BL6 mice underwent 15 minutes of unilateral renal ischemia by clamping of the left renal vascular pedicle (n = 7), or a sham procedure (n = 3), under inhaled general anesthesia by Sevoflurane. A renal ultrasound was performed on the left ischemic kidney at baseline 1 week before the surgery, then, 20 minutes after reperfusion to assess early modifications of renal perfusion, and 1 month after reperfusion to follow chronic modifications. CEUS was performed in supine position by using a high-resolution ultrasonic imaging system (VEVO 3100 Fujifilm Visualsonics, Toronto, Canada) with a MX550D probe fixed in place with an iron support, ensuring the constant imaging plane throughout acquisition. First, a continuous infusion of microbubbles (VS-11913, Fujifilm Visualsonics, Toronto, Canada) was done through the tail vein, then a high mechanical index burst was given to destroy microbubbles when the contrast enhancement had reached a steady state, and finally, low mechanical-index imaging mode was used until, and 30 sec after the contrast agent concentration reached the plateau. Images were recorded and were analyzed using the “destruction-replenishment” fitting model of the Vevo LAB software (Fujifilm Visualsonics, Toronto, Canada). Renal perfusion was estimated by the total renal Blood Volume (rBV) parameter and was expressed as percentage of the baseline value for each animal. Renal function was also assessed by serum urea concentration 1 month after reperfusion, and the long axis lengths of both the kidneys were measured ex vivo after the mice were euthanized. Results Renal perfusion of the ischemic kidney measured by CEUS was significantly decreased as soon as 20 minutes of reperfusion compared to baseline (median 28,8% of baseline value; interquartiles [20,1 – 69,8%]). 1 month after reperfusion, renal perfusion recovered partially but was still significantly decreased compared to baseline (median 79,9% of baseline value; interquartiles [52,8 – 99,9%]) (Figure A). In sham operated mice, renal perfusion did not differ from baseline at 20 minutes or 1 month (p > 0.05). The renal function, assessed by serum urea, was mildly but significantly impaired 1 month after ischemia-reperfusion compared with sham (median serum urea 9,8 vs. 7,6 mmol/L) (p = 0.02), and this was consistent with the observed kidney atrophy in the ischemic group when compared to the contralateral kidney (median long axis length 7,5 vs 10,8 mm) (p = 0.03). Moreover, the decrease of renal perfusion 20 minutes after reperfusion was significantly correlated with the impairment of renal perfusion 1 month after reperfusion (Pearson r = 0.836, p = 0.005) and with the serum urea level at 1 month (Pearson r = -0.710, p = 0.03) (Figure B-C). Conclusion Renal CEUS was able to detect early impairment of renal perfusion as soon as 20 minutes after 15 minutes of renal ischemia in mice, and perfusion was still decreased 1 month after reperfusion, compared to baseline. This early impairment of perfusion was correlated with the chronic decrease of renal perfusion and renal function 1 month after reperfusion. This was also associated with a significant kidney atrophy. CEUS is an interesting non-invasive tool to assess renal lesions dynamically after ischemia-reperfusion.

A dynamic simulation framework for CT perfusion in stroke assessment built from first principles.

Physicians utilize cerebral perfusion maps (e.g., cerebral blood flow, cerebral blood volume, transit time) to prescribe the plan of care for stroke patients. Variability in scanning techniques and post-processing software can result in differences between these perfusion maps. To determine which techniques are acceptable for clinical care, it is important to validate the accuracy and reproducibility of the perfusion maps. Validation using clinical data is challenging due to the lack of a gold standard to assess cerebral perfusion and the impracticality of scanning patients multiple times with different scanning techniques. In contrast, simulated data from a realistic digital phantom of the cerebral perfusion in acute stroke patients would enable studies to optimize and validate the scanning and post-processing techniques. We describe a complete framework to simulate CT perfusion studies for stroke assessment. We begin by expanding the XCAT brain phantom to enable spatially varying contrast agent dynamics and incorporate a realistic model of the dynamics in the cerebral vasculature derived from first principles. A dynamic CT simulator utilizes the time-concentration curves to define the contrast agent concentration in the object at each time point and generates CT perfusion images compatible with commercially available post-processing software. We also generate ground truth perfusion maps to which the maps generated by post-processing software can be compared. We demonstrate a dynamic CT perfusion study of a simulated patient with an ischemic stroke and the resulting perfusion maps generated by post-processing software. We include a visual comparison between the computer-generated perfusion maps and the ground truth perfusion maps. The framework is highly tunable; users can modify the perfusion properties (e.g., occlusion location, CBF, CBV, and MTT), scanner specifications (e.g., focal spot size and detector configuration), scanning protocol (e.g., kVp and mAs), and reconstruction parameters (e.g., slice thickness and reconstruction filter). This framework provides realistic test data with the underlying ground truth that enables a robust assessment of CT perfusion techniques and post-processing methods for stroke assessment.

Spectral CT imaging of human osteoarthritic cartilage via quantitative assessment of glycosaminoglycan content using multiple contrast agents.

Detection of early osteoarthritis to stabilize or reverse the damage to articular cartilage would improve patient function, reduce disability, and limit the need for joint replacement. In this study, we investigated nondestructive photon-processing spectral computed tomography (CT) for the quantitative measurement of the glycosaminoglycan (GAG) content compared to destructive histological and biochemical assay techniques in normal and osteoarthritic tissues. Cartilage-bone cores from healthy bovine stifles were incubated in 50% ioxaglate (Hexabrix®) or 100% gadobenate dimeglumine (MultiHance®). A photon-processing spectral CT (MARS) scanner with a CdTe-Medipix3RX detector imaged samples. Calibration phantoms of ioxaglate and gadobenate dimeglumine were used to determine iodine and gadolinium concentrations from photon-processing spectral CT images to correlate with the GAG content measured using a dimethylmethylene blue assay. The zonal distribution of GAG was compared between photon-processing spectral CT images and histological sections. Furthermore, discrimination and quantification of GAG in osteoarthritic human tibial plateau tissue using the same contrast agents were demonstrated. Contrast agent concentrations were inversely related to the GAG content. The GAG concentration increased from 25 μg/ml (85 mg/ml iodine or 43 mg/ml gadolinium) in the superficial layer to 75 μg/ml (65 mg/ml iodine or 37 mg/ml gadolinium) in the deep layer of healthy bovine cartilage. Deep zone articular cartilage could be distinguished from subchondral bone by utilizing the material decomposition technique. Photon-processing spectral CT images correlated with histological sections in healthy and osteoarthritic tissues. Post-imaging material decomposition was able to quantify the GAG content and distribution throughout healthy and osteoarthritic cartilage using Hexabrix® and MultiHance® while differentiating the underlying subchondral bone.

Simultaneous quantification of SPIO and gadolinium contrast agents using MR fingerprinting

PurposeDevelop a magnetic resonance fingerprinting (MRF) methodology with R2∗ quantification, intended for use with simultaneous contrast agent concentration mapping, particularly gadolinium (Gd) and iron labelled CD8+ T cells. MethodsVariable-density spiral SSFP MRF was used, modified to allow variable TE, and with an exp.(−TE·R2∗) dictionary modulation. In vitro phantoms containing SPIO labelled cells and/or gadolinium were used to validate parameter maps, probe undersampling capacity, and verify dual quantification capabilities. A C57BL/6 mouse was imaged using MRF to demonstrate acceptable in vivo resolution and signal at 8× undersampling necessary for a 25-min scan. ResultsStrong agreement was found between conventional and MRF-derived values for R1, R2, and R2∗. Expanded MRF allowed quantification of iron-loaded CD8+ T cells. Results were robust to 8× undersampling and enabled recreation of relaxation profiles for both a Gd agent and iron labelled cells simultaneously. In vivo data demonstrated sufficient SNR in undersampled data for parameter mapping to visualise key features. ConclusionMRF can be expanded to include R1, R2, and R2∗ mapping required for simultaneous quantification of gadolinium and SPIO in vitro, allowing for potential implementation of a variety of future in vivo studies using dual MR contrast agents, including molecular imaging of labelled cells.

Effect of Applying Leakage Correction on rCBV Measurement Derived From DSC-MRI in Enhancing and Nonenhancing Glioma.

PurposeRelative cerebral blood volume (rCBV) is the most widely used parameter derived from DSC perfusion MR imaging for predicting brain tumor aggressiveness. However, accurate rCBV estimation is challenging in enhancing glioma, because of contrast agent extravasation through a disrupted blood-brain barrier (BBB), and even for nonenhancing glioma with an intact BBB, due to an elevated steady-state contrast agent concentration in the vasculature after first passage. In this study a thorough investigation of the effects of two different leakage correction algorithms on rCBV estimation for enhancing and nonenhancing tumors was conducted.MethodsTwo datasets were used retrospectively in this study: 1. A publicly available TCIA dataset (49 patients with 35 enhancing and 14 nonenhancing glioma); 2. A dataset acquired clinically at Erasmus MC (EMC, Rotterdam, NL) (47 patients with 20 enhancing and 27 nonenhancing glial brain lesions). The leakage correction algorithms investigated in this study were: a unidirectional model-based algorithm with flux of contrast agent from the intra- to the extravascular extracellular space (EES); and a bidirectional model-based algorithm additionally including flow from EES to the intravascular space.ResultsIn enhancing glioma, the estimated average contrast-enhanced tumor rCBV significantly (Bonferroni corrected Wilcoxon Signed Rank Test, p < 0.05) decreased across the patients when applying unidirectional and bidirectional correction: 4.00 ± 2.11 (uncorrected), 3.19 ± 1.65 (unidirectional), and 2.91 ± 1.55 (bidirectional) in TCIA dataset and 2.51 ± 1.3 (uncorrected), 1.72 ± 0.84 (unidirectional), and 1.59 ± 0.9 (bidirectional) in EMC dataset. In nonenhancing glioma, a significant but smaller difference in observed rCBV was found after application of both correction methods used in this study: 1.42 ± 0.60 (uncorrected), 1.28 ± 0.46 (unidirectional), and 1.24 ± 0.37 (bidirectional) in TCIA dataset and 0.91 ± 0.49 (uncorrected), 0.77 ± 0.37 (unidirectional), and 0.67 ± 0.34 (bidirectional) in EMC dataset.ConclusionBoth leakage correction algorithms were found to change rCBV estimation with BBB disruption in enhancing glioma, and to a lesser degree in nonenhancing glioma. Stronger effects were found for bidirectional leakage correction than for unidirectional leakage correction.

Quantitative dual contrast photon-counting computed tomography for assessment of articular cartilage health

Photon-counting detector computed tomography (PCD-CT) is a modern spectral imaging technique utilizing photon-counting detectors (PCDs). PCDs detect individual photons and classify them into fixed energy bins, thus enabling energy selective imaging, contrary to energy integrating detectors that detects and sums the total energy from all photons during acquisition. The structure and composition of the articular cartilage cannot be detected with native CT imaging but can be assessed using contrast-enhancement. Spectral imaging allows simultaneous decomposition of multiple contrast agents, which can be used to target and highlight discrete cartilage properties. Here we report, for the first time, the use of PCD-CT to quantify a cationic iodinated CA4+ (targeting proteoglycans) and a non-ionic gadolinium-based gadoteridol (reflecting water content) contrast agents inside human osteochondral tissue (n = 53). We performed PCD-CT scanning at diffusion equilibrium and compared the results against reference data of biomechanical and optical density measurements, and Mankin scoring. PCD-CT enables simultaneous quantification of the two contrast agent concentrations inside cartilage and the results correlate with the structural and functional reference parameters. With improved soft tissue contrast and assessment of proteoglycan and water contents, PCD-CT with the dual contrast agent method is of potential use for the detection and monitoring of osteoarthritis.

Quantifying MRI T1 relaxation in flowing blood: implications for arterial input function measurement in DCE-MRI.

Objectives:To investigate the feasibility of accurately quantifying the concentration of MRI contrast agent in flowing blood by measuring its T1 in a large vessel. Such measures are often used to obtain patient-specific arterial input functions for the accurate fitting of pharmacokinetic models to dynamic contrast enhanced MRI data. Flow is known to produce errors with this technique, but these have so far been poorly quantified and characterised in the context of pulsatile flow with a rapidly changing T1 as would be expected in vivo.Methods:A phantom was developed which used a mechanical pump to pass fluid at physiologically relevant rates. Measurements of T1 were made using high temporal resolution gradient recalled sequences suitable for DCE-MRI of both constant and pulsatile flow. These measures were used to validate a virtual phantom that was then used to simulate the expected errors in the measurement of an AIF in vivo.Results:The relationship between measured T1 values and flow velocity was found to be non-linear. The subsequent error in quantification of contrast agent concentration in a measured AIF was shown.Conclusions:The T1 measurement of flowing blood using standard DCE- MRI sequences are subject to large measurement errors which are non-linear in relation to flow velocity.Advances in knowledge:This work qualitatively and quantitatively demonstrates the difficulties of accurately measuring the T1 of flowing blood using DCE-MRI over a wide range of physiologically realistic flow velocities and pulsatilities. Sources of error are identified and proposals made to reduce these.

Study on Establishing Reference Safe Concentrations of MRI Contrast Agents for Optimized Images: Paramagnetic Gd-DTPA-BMEA and Superparamagnetic Ferucarbotran

The purpose of this study is to establish the minimal injection doses of magnetic resonance imaging (MRI) contrast agents that can achieve optimized images while improving the safety of injectable MRI drugs. Gadolinium-diethylenetriamine penta-acetic acid (Gd-DTPA) and ferucarbotran, commonly used in clinical practice, were selected and evaluated with in vitro and in vivo experiments. MRI was acquired using T1-weighted (T1W) and T2-weighted (T2W) sequences, and the results were quantitatively analyzed. For in vitro experiments, results showed that T1W and T2W images were optimal when Gd-DTPA-bisamide (2-oxoethyl) (Gd-DTPA-BMEA) and ferucarbotran were diluted to a volume percentage of 0.6% and 0.05%; all comparisons were significant differences in grayscale statistics using one-way analysis of variance (ANOVA). For in vivo experiments, the contrast agent with optimal concentration percentages determined from in vitro experiments were injected into mice with an injection volume of 100 μL, and the images of brain, heart, liver, and mesentery before and after injection were compared. The statistical results showed that the p values of both T1W and T2W were less than 0.001, which were statistically significant. Under safety considerations for MRI contrast agent injection, optimized MRI images could still be obtained after reducing the injection concentration, which can provide a reference for the safety concentrations of MRI contrast agent injection in the future.

Signal intensity form of the Tofts model for quantitative analysis of prostate dynamic contrast enhanced MRI data

The aim of this study is to develop a signal intensity (S(t)) form of the standard Tofts pharmacokinetic model that avoids the need to calculate tissue contrast agent concentration (C(t)) as function of time (t). We refer to this as ‘SI-Tofts’ model. Physiological parameters (K trans and v e) calculated using the SI-Tofts and standard Tofts models were compared by using simulations and human prostate dynamic contrast enhanced (DCE) MRI data. This approach was also applied to the Patlak model to compare K trans values calculated from C(t) and S(t). Simulations were performed on DCE-MRI data from the quantitative imaging biomarkers alliance to validate SI-Tofts model. In addition, ultrafast DCE-MRI data were acquired from 18 prostate cancer patients on a Philips Achieva 3T-TX scanner. Regions-of-interest (ROIs) for prostate cancer, normal tissue, gluteal muscle, and iliac artery were manually traced. The C(t) was calculated for each ROI using the standard model with measured pre-contrast tissue T 1 values. Both the simulation and clinical results showed strong correlation (r = 0.87–0.99, p < 0.001) for K trans and v e calculated from the SI-Tofts and standard Tofts models. The SI-Tofts model with a correction factor using the T 1 ratio of blood to tissue significantly improved the K trans estimates. The correlation of K trans obtained from the Patlak model with C(t) vs S(t) was also strong (r = 0.95–0.99, p < 0.001). These preliminary results suggest that physiological parameters from DCE-MRI can be reliably estimated from the SI-Tofts model without contrast agent concentration calculation.

Analysis Protocol for Dynamic Contrast Enhanced (DCE) MRI of Renal Perfusion and Filtration.

Here we present an analysis protocol for dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) data of the kidneys. It covers comprehensive steps to facilitate signal to contrast agent concentration mapping via T1 mapping and the calculation of renal perfusion and filtration parametric maps using model-free approaches, model free analysis using deconvolution, the Toft's model and a Bayesian approach.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This analysis protocol chapter is complemented by two separate chapters describing the basic concept and experimental procedure.

Ultrasound-assisted fabrication of acoustically active, erythrocyte membrane “bubbles”

In this communication, we report an ultrasound-assisted method, utilising human red blood cell (RBC) or erythrocyte membranes, to produce acoustically active “bubbles”, intended for vasculature imaging. The resulting RBC membrane bubbles have an average size of 1.5 μm with a generally spherical morphology, altered internal aqueous compartment contents, and small gas-containing protrusions or “pockets” in between the membrane bilayer. We also found that this method produced some nanobubbles (200–400 nm diameter), due to the shedding of lipid components from the RBC membranes to compensate for the membrane structural changes. In vitro ultrasound imaging showed that RBC membrane bubbles had comparable ultrasound contrast enhancement as the standard DEFINTYTM microbubble preparation (~13% v/v) and lower concentrations of this standard contrast agent. This current technology demonstrate a new and important application of ultrasound and of RBC membranes, having inherent biocompatibility, as potential material for the development of new types of ultrasound imaging agents, without the use of additional lipid components and pre-made microbubbles.

Experimental studies for noninvasive assessment of portal vein pressure based on contrast enhanced subharmonic sonographic imaging

Portal hypertension (PHT) is a common complication of liver cirrhosis, which could be measured by the means of portal vein pressure (PVP). However, there is no report about an effective and reliable way to achieve noninvasive assessment of PVP so far. In this study, firstly, we collected ultrasound images and echo signals of different ultrasound contrast agent (UCA) concentrations and different pressure ranges in a low-pressure environment based on an in vitro simulation device. Then, the amplitudes of the subharmonics in the echo signal were obtained by ultrasound grayscale image construction and fast Fourier transform (FFT). Finally, we analyzed the relationship between subharmonic amplitude (SA) and bionic portal vein pressure (BPVP) through linear regression. As a result, in the pressure range of 7.5-45 mm Hg and 8-20 mm Hg, the linear correlation coefficients (LCC) between SA and BPVP were 0.927 and 0.913 respectively when the UCA concentration was 1∶3 000, and LCC were 0.737 and 0.568 respectively when the UCA concentration was 1∶6 000. Particularly, LCC was increased to 0.968 and 0.916 respectively while the SAs of two UCA concentrations were used as the features of BPVP. Therefore, the results show a good performance on the linear relationship between SA and BPVP, and the LCC will be improved by using SAs obtained at different UCA concentrations as the features of BPVP. The proposed method provides reliable experimental verification for noninvasive evaluation of PVP through SA in clinical practice, which could be a guidance for improving the accuracy of PVP assessment.

Intravenous Line Phase-Wrap Artifact at Bilateral Axial 3-T Breast MRI: Identification, Analysis, and Solution.

To understand and remove the source of a phase-wrap artifact produced by residual contrast agent in the intravenous line during acquisition of bilateral axial 3-T dynamic contrast material-enhanced (DCE) breast MRI. A two-part study involved a phantom experiment, followed by an institutional review board approved clinical intervention, to evaluate the phase-wrap artifact at MRI. A phantom model evaluated artifact production by using an intravenous line filled with fluids with varying concentrations of gadolinium-based contrast agent (0, 0.4, 0.8, 1.2, 1.6, and 2 mmol/mL) and by positioning the simulated intravenous line within several fields of view (FOV) at 3-T MRI in breast coils. Next, a clinical assessment was performed with a total of 400 patients (control group:interventional group, 200:200) to determine the effect of taping the intravenous line to the patients' backs. Breast MR images were assessed blindly for the presence of the artifact. Software was used for statistical analysis with a P value of less than .05 considered a significant difference. In the phantom model, the artifact was produced only with a 0.4 mmol/mL gadolinium concentration and when the tubing was either close to the edge or within a FOV of 350-450 mm. In the clinical experiment, the artifact was more prevalent in the retrospective control group than in the prospective intervention group (52.5% [105 of 200] vs 22% [44 of 200]; P < .005). The presence of phase-wrap artifacts can be reduced by moving the contrast agent intravenous line out of the FOV during acquisition by taping it to a patient's back during bilateral axial 3-T DCE breast MRI.Keywords: Breast, MR-Imaging, Phantom Studies© RSNA, 2020.

Drug concentration estimation using contrast-enhanced MRI in intra-arterial chemotherapy for head and neck cancers

ObjectiveIn cases of head and neck cancer treated with intra-arterial chemotherapy, no objective indices are available for determining the distribution of anticancer drugs administered to multiple arteries. To establish such indices, noninvasive measurements of drug concentrations are required in the arterial perfusion area of each artery. In MRI, changes in 1/T1 (Δ1/T1) are correlated with the contrast agent concentration. We focused on these properties and investigated whether it is possible to estimate anticancer drug concentrations within tissue based on Δ1/T1. MethodsWe employed the fast spin echo (FSE) sequence to determine optimum imaging parameters using a phantom. Subsequently, contrast agent was administered via the lingual and external carotid arteries for seven cases of tongue cancer. Δ1/T1 were then measured in tumor and nontumor tissues. The results of this study were compared with those of a previous study in which intratumor concentrations of anticancer agent were measured in excised specimens. ResultsThe optimum imaging parameters for the FSE was two repetition times (TR, 500 and 1000 ms). When compared with the external carotid artery administration, the lingual artery administration of contrast agent resulted in significantly higher Δ1/T1 in both tumor and nontumor tissues (2.13 and 2.62 times, respectively). The multiplying factor for the nontumor tissue and high homogeneity of the contrast agent concentration were reasonably consistent with the results of the previous study. ConclusionThis method can be applied to estimating intratissue concentrations of intra-arterially administered anticancer drugs, thus possibly providing useful information in determining the distribution of anticancer drugs.

Catheter-based Arterial Input Function Determination for Myocardial Perfusion Measurements

The quantification of myocardial perfusion with contrast agent (CA) tracers requires the precise knowledge of the arterial input function (AIF). In this study a method for MR-guided vascular interventions is evaluated that determines the AIF via an active tracking catheter during targeted CA injection. A phantom experiment with a dialysis filter was conducted to measure the AIF using an active catheter and a dynamic image series as reference. To compensate for dilution and coil sensitivity effects, correction methods were developed for the catheter-based AIF determination. From the dynamic MR measurements in the perfusion phantom quantitative perfusion maps were calculated by a deconvolution of the measured CA concentration with the AIF, and additional flow measurements were used to normalize the perfusion map. The signal-time-curves of the measured AIF using the catheter-based and imaging-based methods agree while the absolute values differ by a scaling factor of about 9. After normalization to the surrounding flow, both perfusion techniques are in excellent agreement. Catheter-based AIF measurements are feasible but require an additional normalization which can be determined from a flow measurement. The technique might enable faster perfusion measurements during cardiovascular interventions.

In Vitro Investigation of an Electrically Actuated Antireflux Valve for a Multiuse Contrast Agent Injection System.

OBJECTIVE. The purpose of this study was to determine the capability of a newly developed antireflux valve for a multiuse contrast agent injection system. MATERIALS AND METHODS. Multiuse contrast agent injection systems require an antireflux valve to eliminate the risk of cross-patient blood contamination. An electrically actuated antireflux valve developed for this purpose can control risk of contamination because it is under forced control and surveillance. In this study, the injection system was connected to a pulsatile circulation system that reproduced an aortic flow environment in vitro. The transvalvular pressure difference was measured, and flow dynamics during valve opening and closing were visualized by high-speed flow visualization. A total of 30 injection conditions were tested, which included two catheters (6- and 2-French diameter), five contrast agent concentrations (100%, 90%, 50%, 10%, and 0%), and a wide range of flow rates (0.1-25.0 mL/s). RESULTS. The transvalvular pressure difference and flow dynamics during valve opening and closing were characterized. Just before valve opening, a minimum transvalvular pressure difference of 0.20 MPa (1500 mm Hg) was confirmed. The positive pressure difference prevented regurgitation during valve opening. During valve closing, the front of the backflow was monitored continuously, and we confirmed that the front failed to reach the valve before complete closure. CONCLUSION. This study provided proof of concept for an electrically actuated antireflux valve to be used in a multiuse contrast agent injection system.

Spectral photon-counting CT imaging of colorectal peritoneal metastases: initial experience in rats

Computed tomography imaging plays a major role in the preoperative assessment of tumor burden by providing an accurate mapping of the distribution of peritoneal metastases (PM). Spectral Photon Counting Computed Tomography (SPCCT) is an innovative imaging modality that could overcome the current limitations of conventional CT, offering not only better spatial resolution but also better contrast resolution by allowing the discrimination of multiple contrast agents. Based on this capability, we tested the feasibility of SPCCT in the detection of PM at different time of tumor growth in 16 rats inoculated with CC531 cells using dual-contrast injection protocols in two compartments (i.e. intravenous iodine and intraperitoneal gadolinium or the reverse protocol), compared to surgery. For all peritoneal regions and for both protocols, sensitivity was 69%, specificity was 100% and accuracy was 80%, and the correlation with surgical exploration was strong (p = 0.97; p = 0.0001). No significant difference was found in terms of diagnostic performance, quality of peritoneal opacification or diagnostic quality between the 2 injection protocols. We also showed poor vascularization of peritoneal metastases by measuring low concentrations of contrast agent in the largest lesions using SPCCT, which was confirmed by immunohistochemical analyses. In conclusion, SPCCT using dual-contrast agent injection protocols in 2 compartments is a promising imaging modality to assess the extent of PM in a rat model.

Feasibility of free-breathing quantitative myocardial perfusion using multi-echo Dixon magnetic resonance imaging

Dynamic contrast-enhanced quantitative first-pass perfusion using magnetic resonance imaging enables non-invasive objective assessment of myocardial ischemia without ionizing radiation. However, quantification of perfusion is challenging due to the non-linearity between the magnetic resonance signal intensity and contrast agent concentration. Furthermore, respiratory motion during data acquisition precludes quantification of perfusion. While motion correction techniques have been proposed, they have been hampered by the challenge of accounting for dramatic contrast changes during the bolus and long execution times. In this work we investigate the use of a novel free-breathing multi-echo Dixon technique for quantitative myocardial perfusion. The Dixon fat images, unaffected by the dynamic contrast-enhancement, are used to efficiently estimate rigid-body respiratory motion and the computed transformations are applied to the corresponding diagnostic water images. This is followed by a second non-linear correction step using the Dixon water images to remove residual motion. The proposed Dixon motion correction technique was compared to the state-of-the-art technique (spatiotemporal based registration). We demonstrate that the proposed method performs comparably to the state-of-the-art but is significantly faster to execute. Furthermore, the proposed technique can be used to correct for the decay of signal due to T2* effects to improve quantification and additionally, yields fat-free diagnostic images.

Contrast-enhanced micro-computed tomography of articular cartilage morphology with ioversol and iomeprol.

Non-ionic, low-osmolar contrast agents (CAs) used for computed tomography, such as Optiray (ioversol) and Iomeron (iomeprol), are associated with the reduced risk of adverse reactions and toxicity in comparison with ionic CAs, such as Hexabrix. Hexabrix has previously been used for imaging articular cartilage but has been commercially discontinued. This study aimed to evaluate the efficacy of Optiray and Iomeron as alternatives for visualisation of articular cartilage in small animal joints using contrast-enhanced micro-computed tomography (CECT). For this purpose, mouse femora were immersed in different concentrations (20%-50%) of Optiray 350 or Iomeron 350 for periods of time starting at five minutes. The femoral condyles were scanned ex vivo using CECT, and regions of articular cartilage manually contoured to calculate mean attenuation at each time point and concentration. For both CAs, a 30% CA concentration produced a mean cartilage attenuation optimally distinct from both bone and background signal, whilst 5-min immersion times were sufficient for equilibration of CA absorption. Additionally, plugs of bovine articular cartilage were digested by chondroitinase ABC to produce a spectrum of glycosaminoglycan (GAG) content. These samples were immersed in CA and assessed for any correlation between mean attenuation and GAG content. No significant correlation was found between attenuation and cartilage GAG content for either CAs. In conclusion, Optiray and Iomeron enable high-resolution morphological assessment of articular cartilage in small animals using CECT; however, they are not indicative of GAG content.