Behavior of Hepatocellular Adenoma on Real‐time Low‐Mechanical Index Contrast‐Enhanced Ultrasonography With a Second‐Generation Contrast Agent

Objective. The purpose of this study was to describe the behavior of histologically proven hepatocellular adenoma (HCA) on low‐mechanical index (MI) contrast‐enhanced ultrasonography (CEUS). Methods. A review of the databases from 4 academic hospitals revealed 18 patients (15 female and 3 male; mean age, 40 years; range, 25–71 years) with 25 histologically proven HCA lesions who were studied with CEUS at a low MI (0.04–0.1). Results. Twenty‐four of 25 lesions (96%; 95% confidence interval [CI], 80.5%–99.3%) showed high‐intensity enhancement, scored as 3 on a scale of 0 to 3, whereas only 1 lesion (4%; 95% CI, 0.7%–19.5%) was scored as 2. The time of peak enhancement ranged between 10 and 19 seconds (average, 13 seconds). All but 1 of the 25 lesions (96%; 95% CI, 80.5%–99.3%) showed early homogeneous and centripetal enhancement during the hepatic arterial phase. No portal venous phase enhancement was observed in any lesion because all showed rapid wash‐out (100%; 95% CI, 86.7%–100%). Twenty lesions (80%; 95% CI, 60.9%–91.1%) were found to be isoechoic to slightly hypoechoic during the portal phase, and 19 (76%; 95% CI, 56.6%–88.5%) were isoechoic to mildly hypoechoic, whereas 7 (24%; 95% CI, 11.5%–43.4%) were hypoechoic during the late phase. Conclusions. Contrast‐enhanced ultrasonography is an effective technique for identifying the microvascular and macrovascular characteristics of HCA. Typically, HCA shows early (10–19 seconds) and centripetal enhancement during the arterial phase and isoechogenicity or mild hypoechogenicity during the portal phase, remaining slightly hypoechoic or isoechoic during the late phase in most cases.     

Contrast agent comparison for three‐dimensional micro‐CT angiography: A cadaveric study

Barium sulfate and lead oxide contrast media are frequently used for cadaver‐based angiography studies. These contrast media have not previously been compared to determine which is optimal for the visualisation and measurement of blood vessels. In this study, the lower limb vessels of 16 embalmed Wistar rats, and four sets of cannulae of known diameter, were injected with one of three different contrast agents (barium sulfate and resin, barium sulfate and gelatin, and lead oxide combined with milk powder). All were then scanned using micro‐computed tomography (CT) angiography and 3‐D reconstructions generated. The number of branching generations of the rat lower limb vessels were counted and compared between the contrast agents using ANOVA. The diameter of the contrast‐filled cannulae, were measured and used to calculate the accuracy of the measurements by comparing the bias and variance of the estimates. Intra‐ and inter‐observer reliability were calculated using intra‐class correlation coefficients. There was no significant difference (mean difference [MD] 0.05; MD 95% confidence interval [CI] ‐0.83 to 0.93) between the number of branching generations for barium sulfate‐resin and lead oxide‐milk powder. Barium sulfate‐resin demonstrated less bias and less variance of the estimates (MD 0.03; standard deviation [SD] 1.96 mm) compared to lead oxide‐milk powder (MD 0.11; SD 1.96 mm) for measurements of contrast‐filled cannulae scanned at high resolution. Barium sulfate‐resin proved to be more accurate than lead oxide‐milk powder for high resolution micro‐CT scans and is preferred due to its non‐toxicity. This technique could be applied to any embalmed specimen model. Copyright © 2016 John Wiley & Sons, Ltd.     

Synthesis and characterization of new low‐molecular‐weight lysine‐conjugated Gd‐DTPA contrast agents

Various blood pool contrast agents (CAs), characterized by intravascular distribution, have been developed to assist contrast enhanced magnetic resonance angiography (MRA). Among these CAs, the DTPA derivatives conjugated to synthetic polypeptides, such as polylysine, represent attractive candidates for blood pool imaging. However, due to the presence of charged residues located on their backbone, these agents are retained in the kidneys and this compromises their long blood half‐life. In order to overcome this major drawback of the polylysine compounds, two new low‐molecular‐weight CAs were synthesized in the present work by conjugating four or six 1‐p‐isothiocyanatobenzyl‐DTPA moieties to tri‐ or penta‐Lys peptides [(Gd‐DTPA)₄Lys₃ and (Gd‐DTPA)₆Lys₅], respectively. All the –NH₂ groups of Lys were thus blocked by covalent conjugation to DTPA. The stability and relaxometric properties of these compounds, as well as their pharmacokinetic and biodistribution characteristics, were then evaluated. The half‐life in blood of these new polylysine derivatives, as determined in rats, is twofold longer than that of Gd‐DTPA. The compounds could thus be optimal blood pool markers for MRA, which typically uses fast acquisition times. The absence of positive molecular charge did not limit their retention in kidneys 2 h after administration. On the other hand, (Gd‐DTPA)₄Lys₃ is retained in kidneys to a lesser extent than (Gd‐DTPA)₆Lys₅. Their moderate retention in blood and their higher stability and relaxivity in comparison with Gd‐DTPA highlight these polylysine derivatives as optimal compared with previously developed polylysine compounds. Copyright © 2010 John Wiley & Sons, Ltd.     

Design of ProCAs (Protein‐Based Gd3+ MRI Contrast Agents) with High Dose Efficiency and Capability for Molecular Imaging of Cancer Biomarkers

Magnetic resonance imaging (MRI) is the leading imaging technique for disease diagnostics, providing high resolution, three‐dimensional images noninvasively. MRI contrast agents are designed to improve the contrast and sensitivity of MRI. However, current clinically used MRI contrast agents have relaxivities far below the theoretical upper limit, which largely prevent advancing molecular imaging of biomarkers with desired sensitivity and specificity. This review describes current progress in the development of a new class of protein‐based MRI contrast agents (ProCAs) with high relaxivity using protein design to optimize the parameters that govern relaxivity. Further, engineering with targeting moiety allows these contrast agents to be applicable for molecular imaging of prostate cancer biomarkers by MRI. The developed protein‐based contrast agents also exhibit additional in vitro and in vivo advantages for molecular imaging of disease biomarkers, such as high metal‐binding stability and selectivity, reduced toxicity, proper blood circulation time, and higher permeability in tumor tissue in addition to improved relaxivities.     

Contrast enhancement by lipid‐based MRI contrast agents in mouse atherosclerotic plaques; a longitudinal study

The use of contrast‐enhanced MRI to enable in vivo specific characterization of atherosclerotic plaques is increasing. In this study the intrinsic ability of two differently sized gadolinium‐based contrast agents to enhance atherosclerotic plaques in ApoE^?/? mice was evaluated with MRI. We obtained a kinetic profile for contrast enhancement, as the literature data on optimal imaging time points is scarce, and assessed the longer‐term kinetics. Signal enhancement in the wall of the aortic arch, following intravenous injection of paramagnetic micelles and liposomes, was followed for 1 week. In vivo T₁‐weighted MRI plaque enhancement characteristics were complemented by fluorescence microscopy of NIR₆₆₄ incorporated in the contrast agents and quantification of tissue and blood Gd–DTPA. Both micelles and liposomes enhanced contrast in T₁‐weighted MR images of plaques in the aortic arch. The average contrast‐to‐noise ratio increased after liposome or micelle injection to 260 or 280% respectively, at 24 h after injection, compared with a pre‐scan. A second wave of maximum contrast enhancement was observed around 60–72 h after injection, which only slowly decreased towards the 1 week end‐point. Confocal fluorescence microscopy and whole body fluorescence imaging confirmed MRI‐findings of accumulation of micelles and liposomes. Plaque permeation of contrast agents was not strongly dependent on the contrast agent size in this mouse model. Our results show that intraplaque accumulation over time of both contrast agents leads to good plaque visualization for a long period. This inherent intraplaque accumulation might make it difficult to discriminate passive from targeted accumulation. This implies that, in the development of targeted contrast agents on a lipid‐based backbone, extensive timing studies are required. Copyright © 2012 John Wiley & Sons, Ltd.     

MRI tumor characterization using Gd‐GlyMe‐DOTA‐perfluorooctyl‐mannose‐conjugate (Gadofluorine M™), a protein‐avid contrast agent

The rationale and objectives were to define the MRI tumor‐characterizing potential of a new protein‐avid contrast agent, Gd‐GlyMe‐DOTA‐perfluorooctyl‐mannose‐conjugate (Gadofluorine M?; Schering AG, Berlin, Germany) in a chemically induced tumor model of varying malignancy. Because of the tendency for this agent to form large micelles in water and to bind strongly to hydrophobic sites on proteins, it was hypothesized that patterns of dynamic tumor enhancement could be used to differentiate benign from malignant lesions, to grade the severity of malignancies and to define areas of tumor necrosis. Gadofluorine M, 0.05 mmol Gd kg^?1, was administered intravenously to 28 anesthetized rats that had developed over 10 months mammary tumors of varying degrees of malignancy as a consequence of intraperitoneal administration of N‐ethyl‐N‐nitrosourea (ENU), 45–250 mg kg^?1. These tumors ranged histologically from benign fibroadenomas to highly undifferentiated adenocarcinomas. Dynamic enhancement data were analyzed kinetically using a two‐compartment tumor model to generate estimates of fractional plasma volume (fPV), apparent fractional extracellular volume (fEV*) and an endothelial transfer coefficient (K^PS) for this contrast agent. Tumors were examined microscopically for tumor type, degree of malignancy (Scarff–Bloom–Richardson score) and location of necrosis. Eighteen tumor‐bearing rats were successfully imaged. MRI data showed an immediate strong and gradually increasing tumor enhancement. K^PS and fEV*, but not fPV obtained from tumors correlated significantly (p < 0.05) with the SBR tumor grade, r = 0.65 and 0.56, respectively. Estimates for K^PS and fEV* but not fPV were significantly lower in a group consisting of benign and low‐grade malignant tumors compared with the group of less‐differentiated high‐grade tumors (1.61 ± 0.64 vs 3.37 ± 1.49, p < 0.01; 0.45 ± 0.17 vs 0.78 ± 0.24, p < 0.01; and 0.076 ± 0.048 vs 0.121 ± 0.088, p = 0.24, respectively). It is concluded that the protein‐avid MRI contrast agent Gadofluorine M enhances tumors of varying malignancy depending on the tumor grade, higher contrast agent accumulation for more malignant lesions. The results show potential utility for differentiating benign and low‐grade malignant lesions from high‐grade cancers. Copyright © 2006 John Wiley & Sons, Ltd.     

能量多普勒造影技术在经静脉心肌声学造影研究中的临床初步应用

目的：观察能量多普勒造影技术（ＰＣＩ）行静脉心肌声学造影（ＭＣＥ）的效果。方法：利用ＰＣＩ技术观察６例非特异性胸痛患者及３例陈旧性心肌梗塞患者的经静脉心肌声学造影效果。其中,心肌梗塞患者在ＭＣＥ后一周内行核素检查。结果：６例非特异性胸痛患者均未见节段室壁运动异常,在声学造影剂注射后见全部心肌组织均匀显影 ３例陈旧性心肌梗塞患者则见梗塞相应部位室壁运动异常,且声学造影检查发现该部位多普勒能量信号缺失     

Contrast‐Enhanced Colosonography for the Evaluation of Children With an Imperforate Anus

This case series describes a novel method for showing the preoperative anatomy of children with anorectal malformations using ultrasound contrast, which we have termed “contrast‐enhanced colosonography (ceCS).” Six patients with anorectal malformations without a perineal fistula were studied both by fluoroscopic distal colostography and ceCS, and their results were confirmed surgically. Contrast‐enhanced CS precisely showed the complex anatomic relationships in all cases. Compared to traditional fluoroscopic studies, ceCS has the benefit of no associated ionizing radiation and thus is safer for children.