Interstitial magnetic resonance lymphography using a polymeric t1 contrast agent: initial experience with Gadomer-17

RATIONALE AND OBJECTIVES: The detection of lymph node metastases is an important step in tumor staging and is significant for therapy planning. Lymph node-specific contrast agents can raise the sensitivity and specificity of modern diagnostic methods. This study investigated the suitability of the dendritic contrast agent Gadomer-17 in magnetic resonance (MR) lymph node imaging and compared three different dosages in such an application. METHODS: Doses of 1.0, 2.5, and 10.0 micromol Gd/kg body weight were interstitially injected into the hind legs of dogs; the signal intensities of two successive lymph node groups (inguinal and iliacal) were then recorded up to 120 minutes after injection. RESULTS: Gadomer-17 induced a strong increase in signal intensity of the examined lymph node groups. At 15 minutes postinjection, the enhancement increased by 120% to 680%, depending on the dose. The maximum enhancement was 450% to 960% at 60 to 90 minutes postinjection. Doses of 2.5 and 10.0 micromol Gd/kg showed comparable results; even the lowest dose (1.0 micromol Gd/kg) enhanced the contrast of the inguinal lymph nodes in 4 of 5 animals and the iliacal lymph nodes in three of five animals. Therefore, the minimum effective dose of Gadomer-17 in this study was approximately 2.5 micromol Gd/kg. CONCLUSION: This study revealed the excellent suitability of the dendritic contrast agent Gadomer-17 for MR imaging of the lymphatic system (lymph nodes and lymph vessels).     

Pre-clinical evaluation of gadobutrol: a new,neutral, extracellular contrast agent for magnetic resonance imaging

The Gd³⁺-complex of 10-(2,3-dihydroxy-l-hydroxymethylpropyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (gadobutrol) is a new, neutral Gd-chelate for use as an extracellular contrast agent in magnetic resonance imaging (MRI). The blood level in dogs after intravenous (i.v.) injection decreased with a terminal half-life of about 45 min, the clearance was about 3.75 ml/min per kg and the distribution volume of 0.23 l/kg suggested an extracellular distribution. Biodistribution experiments in rats revealed that only a very small amount (0.16%) of the dose was left in the body 7 days after i.v. injection. Measurable amounts of Gd could be detected only in the liver, kidneys and bones. The osmolality (0.57 osmol/kg at 0.5 mol/1 and 1.39 osmol/kg at 1 mol/1) is in the range of other low osmolality contrast media for MRI. Only very little interaction with biologically relevant molecules was suggested by a histamine release test and a lysozyme inhibition test. An i.v.-LD₅₀ of 23 mmol/kg in mice combined with a comparatively high T₁-relaxivity (5.6 l/mmol per s at 0.47 T and 6.1 l/mmol per s at 2 T) in plasma promises a high margin of safety. In preliminary imaging experiments, gadobutrol caused high enhancement in different lesions (cerebral infarct, brain tumor) of the rat. Tripling of the typical clinical dose of 0.1 mmol/kg was shown to provide additional diagnostic gain in lesions of this type.     

Interstitial magnetic resonance lymphography using gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid in rabbits with lymph node metastasis

RATIONALE AND OBJECTIVES: To investigate the dose dependency of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) for interstitial magnetic resonance (MR) lymphography and the detection of lymph node metastasis in rabbits. METHODS: Eighteen VX2 tumor-bearing rabbits were subjected to MR lymphography using clinical MRI equipment. The enhancement of popliteal lymph nodes was studied in these rabbits before and at 2.5 to 10 minutes after the subcutaneous administration of 4, 8, or 17 micromol Gd/kg of Gd-EOB-DTPA in TSE and 3D-FLASH (n = 6). Signal-to-noise ratio and contrast-to-noise ratio were statistically compared between each group by the Tukey test. After MR imaging, the popliteal lymph nodes were removed, and sections were prepared for microscopic examination. RESULTS: In the histologic findings, all metastases (3-12 mm) in the popliteal lymph nodes were detected by 3D-FLASH images. Gd-EOB-DTPA-enhanced T1WI showed a hypointense region for metastasis and a hyperintense region for nontumor regions, although the lymph nodes containing metastasis were detected as a hyperintense region by conventional PDWI and T2WI. Signal enhancement of the nontumor regions and contrast between the nontumor regions and metastasis showed dose dependency and reached a plateau at 8 micromol Gd/kg on T1WI (signal-to-noise ratio: 13.9 +/- 1.6; contrast-to-noise ratio: -12.7 +/- 1.7). CONCLUSIONS: This study showed that interstitial MR lymphography with Gd-EOB-DTPA can detect metastasis and that the optimal dose in rabbits is 8 micromol Gd/kg as a subcutaneous application.     

Interstitial magnetic resonance lymphography: comparative animal study of gadofluorine 8 and gadolinium diethylenetriamine-pentaacetic acid

PURPOSE: We evaluated the usefulness of gadofluorine 8 (G8) and gadolinium diethylenetriamine-pentaacetic acid (Gd-DTPA) for interstitial magnetic resonance lymphography (MRL). METHOD: Phantom imaging studies were conducted with G8 and Gd-DTPA corresponding to 0.1-0.005 micromol Gd/mL, and signal intensity was measured. Popliteal lymph node (PLN) accumulation was investigated in rabbits. Imaging was performed before and after subcutaneous administration of G8 (50 micromol Gd/mL) and Gd-DTPA (50 micromol Gd/mL). Contrast enhancement ratio measurements of PLN were determined both prior to and following the administration. RESULTS: Signal intensity of phantom for G8 are higher than those for Gd-DTPA from 0.1 to 0.002 micromol Gd/mL (P < 0.0001). Imaging after 5 minutes can clearly detect PLN accumulation on two contrast agents. Nevertheless, PLN accumulation of Gd-DTPA disappeared after about 30 minutes. A statistically significant difference between G8 and Gd-DTPA can be seen from 5 to 90 minutes in CER (P < 0.0001). PLN became clearly visible at 5 minutes after the injection of G8 and Gd-DTPA. Nevertheless, PLN accumulation of Gd-DTPA disappeared at 30 minutes. Otherwise, PLN accumulation of G8 continued up to 90 minutes. CONCLUSION: These studies indicated that G8 was more suitable than Gd-DTPA as a contrast agent for interstitial MRL up to 90 minutes.     

Macrocyclic contrast agents for magnetic resonance imaging of chronic myocardial infarction: intraindividual comparison of gadobutrol and gadoterate meglumine

Objectives

To compare 0.15?mmol/kg gadobutrol for late gadolinium enhancement (LGE) imaging of chronic myocardial infarction with a relaxivity-adjusted dose of gadoterate meglumine (Gd-DOTA).

Methods

Seventeen patients with suspected chronic myocardial infarction underwent LGE imaging at 1.5 T, acquiring an inversion-recovery-prepared gradient echo sequence 15?min after contrast agent administration. Each patient underwent LGE imaging twice, once after administration of 0.15?mmol/kg gadobutrol (r1?=?5.2?l?mmol^-1?s^-1) and after 0.22?mmol/kg Gd-DOTA (r1?=?3.6?l?mmol^-1?s^-1). Two readers independently determined infarct size and contrast-to-noise ratios of infarcted myocardium to remote myocardium (CNR_remote) and to the left ventricular lumen (CNR_lumen).

Results

LGE was present in 14 patients. Infarct sizes determined after administration of gadobutrol [23.4?ml; 95?% CI (14.4; 32.5)] and Gd-DOTA [22.1?ml; 95?% CI (13.0; 31.1)] were not statistically different (P?=?0.22). The CNR_remote of LGE in infarcted myocardium on gadobutrol- and Gd-DOTA-enhanced images was 44.1 [95?% CI (31.0; 57.1)] and 45.2 [95?% CI (32.2; 58.3)], respectively (P?=?0.73). CNR_lumen was significantly higher on gadobutrol-enhanced LGE images [12.7; 95?% CI (2.5; 23.0) versus 6.8; 95?% CI (-3.5; 17.0); P?=?0.02].

Conclusion

At relaxivity-adjusted doses, gadobutrol and Gd-DOTA yielded similar infarct sizes with superior contrast between infarcted myocardium and left ventricular lumen on gadobutrol-enhanced images.

Key points

? Contrast-enhanced magnetic resonance imaging is increasingly used to assess the myocardium ? Macrocyclic Gd-based contrast agents are considered to be safer than linear agents ? Myocardial infarction MRI can be performed using either gadobutrol or gadoterate meglumine ? Contrast between infarcted myocardium and the left ventricular lumen was greater using gadobutrol ? The minimum macrocyclic dose needed for reliable LGE imaging requires further evaluation     

Post-marketing surveillance of gadobutrol for contrast-enhanced magnetic resonance imaging in Japan

Purpose

To evaluate the safety of gadobutrol for magnetic resonance imaging in a prospective, non-interventional, post-marketing surveillance in Japan.

Materials and methods

Gadobutrol was administered in accordance with Japanese prescribing information over a 2-year enrollment period, using a standardized questionnaire to collect information. The primary outcome was the incidence of adverse reactions (ARs) following gadobutrol injection.

Results

Questionnaire data were analyzed for 3337 patients (age, 58.1?±?17.4 years [mean±SD]). Gadobutrol was administered at a dose of 0.10?±?0.02 mL/kg body weight. Thirty-three patients were observed to have 42 ARs suspected to be due to gadobutrol, an incidence proportion of 0.99%; 29 ARs were acute (<1 h post-injection)—including one case of severe acute AR (0.03%). Patient subpopulations (with hepatic, renal, cardiovascular diseases) did not differ markedly in AR proportions categorized by age, sex, presence of comorbidity, or imaging indication. No cases of nephrogenic systemic fibrosis were reported. Investigators rated images as improved or profoundly improved following gadobutrol injection in 91.1% of examinations.

Conclusion

Gadobutrol was well tolerated with a good safety profile in this post-marketing surveillance of a large patient population in Japan.

     

Use of a personal computer in contrast evaluation in magnetic resonance tomography

Contrast dependency in MR Tomography from several intrinsic and extrinsic parameters makes this technique versatile and sensitive; at the same time it makes more complex the image contrast evaluation and the optimized sequence choice. The approach to this problem from the viewpoint both of training and practical application becomes easier using the proposed personal computer program.     

Interstitial MR lymphography with gadoterate meglumine: initial experience in humans

Magnetic resonance (MR) lymphography was performed in five healthy volunteers and three patients (two adults and one infant). Subcutaneous administration of gadoterate meglumine in the foot allowed visualization of draining lymph vessels and nodes. In one patient, an inguinal fluid collection could be characterized as a lymphocele. In the infant, a chylothorax was diagnosed. The authors conclude that interstitial MR lymphography with commercially available compounds is feasible.     

Preliminary evaluation of EVP 1001-1: a new cardiac-specific magnetic resonance contrast agent with kinetics suitable for steady-state imaging of the ischemic heart

RATIONALE AND OBJECTIVES: To investigate the potential of a novel manganese-based magnetic resonance (MR) contrast agent, EVP 1001-1 for the evaluation of myocardial ischemia. METHODS: MR imaging with EVP 1001-1 was performed on 6 Yorkshire pigs, and T1 relaxation times were calculated. One animal served as a control, 2 were subjected to an acute coronary artery occlusion and 3 provided a model of chronic ischemia. RESULTS: Administration of the agent in the control and acute coronary occlusion model demonstrated a short plasma half-life (approximately 1.5 minutes) and rapid myocardial uptake in nonoccluded regions, with long retention times in the myocardium (>1 hour) and no evidence of redistribution. In the chronic ischemia model, differential enhancement was observed between normal and ischemic tissue, particularly under dobutamine-induced stress. CONCLUSIONS: These properties suggest the use of EVP 1001-1 for steady-state imaging of myocardial perfusion. Contrast administration could be performed under stress conditions outside the scanner, with high-resolution MR images reflecting the stress condition acquired after the stress has subsided.     

Theoretical-experimental comparison of contrast in magnetic resonance

The intensity of MR signal depends on several parameters, such as proton density [N(H)], relaxation times (T1 and T2), repetition time (TR), and echo time (TE). A theoretical model describes this dependence, which is currently employed for image optimization. It allows the evaluation of image contrast once the tissue parameters are known. The above-mentioned theoretical model was tested with the use of CuSO4 samples at various concentrations for which T1 and T2 values were known from the literature. Our unit was an ESATOM MR 5000 which employed a 0.5 Tesla magnetic field. We used spin-echo sequences with TR = 500, 1000 ms and TE ranging from 50 to 150 ms. Signal intensity was measured both by direct access to the data matrix and with the use of the pixel intensity calculation program for regions of interest. The difference in the signals corresponding to the various samples were determined to evaluate the contrast. Our results are in strict agreement with those from the theoretical model. The latter can thus be employed for image optimization.     

Pineapple juice as a negative oral contrast agent in magnetic resonance cholangiopancreatography: a preliminary evaluation

The quality of magnetic resonance cholangiopancreatography (MRCP) images is frequently degraded by high signal from the gastrointestinal tract. The aim of this study is to evaluate pineapple juice (PJ) as an oral negative contrast agent in MRCP. Preliminary in vitro evaluation demonstrated that PJ shortened T(2) relaxation time and hence decreased T(2) signal intensity on a standard MRCP sequence to a similar degree to a commercially available negative contrast agent (ferumoxsil). Electrothermal atomic absorption spectrometry assay demonstrated a high manganese concentration in PJ of 2.76 mg dl(-1), which is likely to be responsible for its T(2) imaging properties. MRCP was subsequently performed in 10 healthy volunteers, before and at 15 min and 30 min following ingestion of 400 ml of PJ. Images were assessed blindly by two Consultant Radiologists using a standard grading technique based on contrast effect (degree of suppression of bowel signal), and image effect (diagnostic quality). There were statistically significant improvements in contrast and image effect between pre and post PJ images. There was particularly significant improvement in visualization of the pancreatic duct, but no significant difference between 15 min and 30 min post PJ images. Visualization of the ampulla, common bile duct, common hepatic and central intrahepatic ducts were also significantly improved at 15 min following PJ. Our results demonstrate that PJ, may be used as an alternative to commercially available negative oral contrast agent in MRCP.     

Time-resolved imaging of contrast kinetics three-dimensional (3D) magnetic resonance venography in patients with pelvic congestion syndrome

The purpose of this study was to assess the role of magnetic resonance venography (MRV) with time-resolved imaging of contrast kinetics (TRICKS) in dynamically evaluating ovarian vein dilation, reflux and direction of flow in patients with suspected pelvic congestion syndrome (PCS). The hypotheses tested were: (i) That conspicuity scores of the ovarian veins across three raters was greater using TRICKS MRV compared with T2W or T₂* imaging; (ii) That three key MR variables (ovarian vein diameter, timing and grade of reflux) correlated across all raters. We carried out a retrospective study of 13 patients undergoing T2W and TRICKS MRI and pelvic sonography (n = 4) or catheter venography (n = 5). Three observers rated conspicuity, vessel diameter, timing and grade of ovarian vein reflux for T₂/T2*W and TRICKS MRI. The mean left ovarian diameter for all patients with reflux was 7.9 mm (range 2.2–12 mm). There was high inter-observer agreement for ovarian vein diameter for both sequences. TRICKS showed significantly greater conspicuity than T₂/T2*W imaging (TRICKS: T₂/T2* mean (SD) = 7.80 (3.20):5.50 (1.97), F (1,12) = 5.80, p< 0.05). TRICKS MRV demonstrated high inter-observer correlation for timing and grade of reflux (r (36) = 0.77,0.71,0.79, p < 0.01). TRICKS MRA/V was significantly degraded by breathing artefact in two patients. We conclude that TRICKS MRV accurately and dynamically demonstrates ovarian vein reflux in patients with PCS but requires quiet respiration. TRICKS MRV has better image conspicuity than T₂/T2*W imaging and sufficient temporal resolution to distinguish between Grade I, II and III reflux.The purpose of this study was to assess the role of time-resolved imaging of contrast kinetics magnetic resonance venography (TRICKS MRV) in dynamically evaluating ovarian vein dilation, reflux and direction of flow in patients with suspected pelvic congestion syndrome (PCS). PCS is the presence of long-standing pelvic pain due to a variety of causes, including ovarian vein incompetence [1]. The most important aetiological factor is parity, which is associated with ovarian vein dilation and valvular incompetence in 50–73% of women; although it is important to note that not all women with ovarian vein incompetence are symptomatic [1–3]. In women whose PCS is caused by ovarian vein incompetence, surgical ligation or transcatheter ovarian vein embolisation can be successful [4, 5]. To select patients suitable for surgical or interventional therapy, the ideal diagnostic technique has high spatial and temporal resolution, is non-invasive and does not involve ionising radiation. One such technique may be TRICKS MRV, a modified 3D fast gradient echo (GRE) pulse sequence [6]. Here we evaluate the role of TRICKS MRV in assessing ovarian veins, including image conspicuity, spatial and temporal resolution.     

Positive contrast magnetic resonance imaging of cells labeled with magnetic nanoparticles.

Contrast agents incorporating superparamagnetic iron-oxide nanoparticles have shown promise as a means to visualize labeled cells using MRI. Labeled cells cause significant signal dephasing due to the magnetic field inhomogeneity induced in water molecules near the cell. With the resulting signal void as the means for detection, the particles behave as a negative contrast agent, which can suffer from partial-volume effects. In this paper, a new method is described for imaging labeled cells with positive contrast. Spectrally selective RF pulses are used to excite and refocus the off-resonance water surrounding the labeled cells so that only the fluid and tissue immediately adjacent to the labeled cells are visible in the image. Phantom, in vitro, and in vivo experiments show the feasibility of the new method. A significant linear correlation (r = 0.87, P < 0.005) between the estimated number of cells and the signal was observed.