Time Course Of Contrast Enhancement Research Articles

Time Course of Contrast Enhancement by Micro-CT with Dedicated Contrast Agents in Normal Mice and Mice with Hepatocellular Carcinoma: Comparison of One Iodinated and Two Nanoparticle-Based Agents

The aim of the present study was to characterize the kinetics of two nanoparticle-based contrast agents for preclinical imaging, Exitron nano 6000 and Exitron nano 12000, and the iodinated agent eXIA 160 in both healthy mice and in a mouse model of hepatocellular carcinoma (HCC). Semiautomatic segmentation of liver lesions for estimation of total tumor load of the liver was evaluated in HCC mice. The normal time course of contrast enhancement was assessed in 15 healthy C57BL/6 mice. Imaging of tumor spread in the liver was evaluated in 15 mice harboring a transgenic HCC model (ASV-B mice). Automatic segmentation of liver lesions for determination of total tumor burden of the liver was tested in three additional ASV-B mice before and after an experimental therapy. In healthy mice, clearance of the contrast agent from blood was completed within 3-4hours for eXIA 160 and Exitron nano 6000, whereas complete blood clearance of Exitron nano 12000 required about 24hours. eXIA 160 provided maximum liver contrast at 1hour post injection (p.i.) followed by a continuous decline. Enhancement of liver contrast with Exitron nano 6000 and Exitron nano 12000 reached a plateau at about 4hours p.i., which lasted until the end of the measurements at 96hours p.i. Maximum contrast enhancement of the liver was not statistically different between Exitron nano 6000 and Exitron nano 12000, but was about three times lower for eXIA 160 (P<.05). Visually Exitron nano 12000 provided the best liver-to-tumor contrast. Semiautomatic liver and tumor segmentation was feasible after the administration of Exitron nano 12000 but did not work properly for the other two contrast agents. Both nanoparticle-based contrast agents provided stronger and longer lasting contrast enhancement of healthy liver parenchyma. Exitron nano 12000 allowed automatic segmentation of tumor lesions for estimation of the total tumor load in the liver.

Serial Scans in Healthy Volunteers Following Intravenous Administration of Gadoteridol: Time Course of Contrast Enhancement in Various Cranial Fluid Spaces

Heavily T2-weighted, 3-dimensional, fluid-attenuated inversion recovery (hT2W-3D-FLAIR) imaging has been reported to detect low concentrations of gadolinium-based contrast media (GBCM) in the anterior eye segment (AES), subarachnoid space (SAS), and labyrinthine perilymph as well as in the cerebrospinal fluid (CSF) of the internal auditory canal (IAC) 4 hours after intravenous administration of a single dose (IV-SD-GBCM) in patients with inner ear disorders. To elucidate the time course of contrast enhancement in healthy volunteers, we obtained hT2W-3D-FLAIR serially after IV-SD-GBCM. We obtained hT2W-3D-FLAIR before and 0.5, 1.5, 3, 4.5 and 6 hours after IV-SD-GBCM in 6 healthy volunteers and measured signal intensity of the AES, SAS surrounding the optic nerve (SAS-ON), SAS in Meckel's cave (SAS-MC), pontine parenchyma, CSF in the IAC (CSF-IAC), CSF in the ambient cistern (CSF-AC), CSF in the lateral ventricles (CSF-LV), perilymph (PL), and endolymph (EL) in the labyrinth. We then compared averaged values among all time points using analysis of variance (ANOVA). After IV-SD-GBCM, we observed no change in signal intensity in the pontine parenchyma, CSF-LV, or EL and significant enhancement in all other structures. Maximum enhancement was most frequent at 4.5 hours after IV-SD-GBCM in the SAS-ON and PL, at 1.5 hours in the AES and SAS-MC, and at 3 hours in the CSF-IAC and CSF-AC. Contrast enhancement can be detected by hT2W-3D-FLAIR in the AES, SAS-ON, SAS-MC, PL, CSF-IAC, and CSF-AC in healthy volunteers after IV-SD-GBCM. Timing of maximum enhancement differed among locations. These data might serve as basic knowledge for future clinical research.

Use of eXIA 160 XL for Contrast Studies in Micro–Computed Tomography: Experimental Observations

The purpose of this study was to evaluate the time course of contrast enhancement of spleen, liver, and blood using eXIA 160 XL in healthy mice. eXIA 160 XL was intravenously injected in C57bl/6 mice (n = 12) at a dose of 0.1 mL/20 g (16 mg iodine [I]/20 g) (n = 6) or 0.2 mL/20 g (32 mg I/20 g) (n = 6). The distribution was analyzed by repeated micro-computed tomographic scans up to 48 hours after contrast administration. Images were analyzed using Amide software. Regions of interest were drawn in the spleen, liver, and left ventricle. Contrast enhancement was measured and expressed as a function of time. Peak contrast enhancement of the spleen was reached at 30 minutes, and peak contrast enhancement of the liver occurred 45 minutes after 16 mg I/20 g. Given that this contrast was found to be rather low in the spleen in comparison with former eXIA 160 products, experiments were done at a higher dose. However, the 32 mg I/20 g dose was lethal for mice. Enhancement inside the heart lasts for 1 hour. Administration of eXIA 160 XL results in long-lasting blood pool contrast with higher contrast enhancement in heart and liver in comparison with eXIA 160; however, the administered dose should be limited to 16 mg I/20 g.

Micro-CT Based Experimental Liver Imaging Using a Nanoparticulate Contrast Agent: A Longitudinal Study in Mice

BackgroundMicro-CT imaging of liver disease in mice relies on high soft tissue contrast to detect small lesions like liver metastases. Purpose of this study was to characterize the localization and time course of contrast enhancement of a nanoparticular alkaline earth metal-based contrast agent (VISCOVER ExiTron nano) developed for small animal liver CT imaging.MethodologyExiTron nano 6000 and ExiTron nano 12000, formulated for liver/spleen imaging and angiography, respectively, were intravenously injected in C57BL/6J-mice. The distribution and time course of contrast enhancement were analysed by repeated micro-CT up to 6 months. Finally, mice developing liver metastases after intrasplenic injection of colon carcinoma cells underwent longitudinal micro-CT imaging after a single injection of ExiTron nano.Principal FindingsAfter a single injection of ExiTron nano the contrast of liver and spleen peaked after 4–8 hours, lasted up to several months and was tolerated well by all mice. In addition, strong contrast enhancement of abdominal and mediastinal lymph nodes and the adrenal glands was observed. Within the first two hours after injection, particularly ExiTron nano 12000 provided pronounced contrast for imaging of vascular structures. ExiTron nano facilitated detection of liver metastases and provided sufficient contrast for longitudinal observation of tumor development over weeks.ConclusionsThe nanoparticulate contrast agents ExiTron nano 6000 and 12000 provide strong contrast of the liver, spleen, lymph nodes and adrenal glands up to weeks, hereby allowing longitudinal monitoring of pathological processes of these organs in small animals, with ExiTron nano 12000 being particularly optimized for angiography due to its very high initial vessel contrast.

A fast black-blood sequence for four-dimensional cardiac manganese-enhanced MRI in mouse

The increasing number of mouse models of cardiac diseases requires improvements in the current MRI tools. Anatomic and functional cardiac phenotyping by MRI calls for both time and space resolution in three dimensions. Black-blood contrast is often needed for the accurate delineation of myocardium and chambers, and is consistent with manganese contrast enhancement. In this article, we propose a fast, three-dimensional, time-resolved (four-dimensional), black-blood MRI sequence that allows mouse heart imaging at 10 periods of the cardiac cycle within 30 min at an isotropic resolution of 200 µm. Two-dimensional imaging was possible within 80 s. Blood cancellation was achieved by employing bipolar gradients without the use of a double inversion recovery preparation scheme. Saturation slices were added in two-dimensional experiments for better blood nulling. The rapidity of the two-dimensional acquisition protocol allowed the measurement of the time course of contrast enhancement on manganese infusion. Owing to the very high contrast-to-noise ratio, manganese-enhanced MRI in four dimensions made possible the accurate assessment of regional cardiac volumes in healthy animals. In experimentally infarcted mice, the size of the ischemic zone could be measured easily with this method. The technique might be valuable in evaluating mouse heart diseases and their follow-up in longitudinal studies.

Contrast-enhanced dynamic magnetic resonance imaging of finger joints in osteoarthritis and rheumatoid arthritis: an analysis based on pharmacokinetic modeling

To investigate a two-compartment kinetic model applied to the dynamic time course of contrast enhancement as a method to differentiate between finger-joint synovitis in established osteoarthritis (OA) and rheumatoid arthritis (RA). Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of one hand in 19 patients and six healthy volunteers was undertaken. Eight patients had OA of the hand and eleven patients had RA. From the signal intensity curves, the three parameters Kps (endothelial transfer constant), Kep (elimination rate constant from extracellular space back to plasma) and Kel (elimination rate constant from plasma by renal excretion) were calculated. The rate constant Kps showed the best separation between the groups with significantly higher values in the RA group compared to the OA group (P<0.005) and in the OA group compared to the control group (P<0.005). Significantly higher values of Kep were also found in the RA group compared with the OA group (P<0.005). DCE-MRI may provide useful information that can help differentiate synovitis in OA from synovitis in RA.

Sequential contrast-enhanced magnetic resonance imaging in the diagnosis of growth hormone deficiencies.

The purpose of the present study was to assess the presence and the time-course of contrast-enhancement in the pituitary gland and pituitary stalk of 24 patients with isolated growth hormone (GH) deficiency and multiple pituitary hormone deficiency. The patients were evaluated clinically (auxological measurements), endocrinologically (spontaneous GH secretion and GH stimulation tests) and with conventional MRI scans. In addition, fast-framing dynamic magnetic resonance imaging (MRI) with Gd-DTPA enhancement was used to quantitate the time course of contrast enhancement within the neurohypophysis, pituitary stalk, postero-superior adenohypophysis and antero-inferior adenohypophysis. In 3 patients without evidence of abnormalities at normal conventional MRI scans (normal anterior lobe and pituitary stalk, normal posterior lobe) and a high response to the GRF provocation test, sequential time-resolved Gd-enhanced MRI demonstrates reduced contrast enhancement in the pituitary stalk. These findings are consistent with impairment in stalk vasculature, presumably located at the level of the portal venous system, and could play a role in the pathogenesis of pituitary hormonal deficiency.