Gadolinium Diethylenetriaminepentaacetic Acid Bismethylamide Research Articles

Enhanced oval window and blocked round window passages for middle–inner ear transportation of gadolinium in guinea pigs with a perforated round window membrane

To elucidate the communication between the middle and inner ear, and the fluid dynamics of the inner ear with the perilymphatic fistula (PLF) of the round window membrane (RWM). The PLF of the RWM was created in nine guinea pigs. Gadolinium diethylenetriamine pentaacetic acid bismethylamide (Gd-DTPA-BMA) was delivered into the middle ear and followed in the inner ear using a 4.7 Tesla MRI. Pressure was delivered to the external ear canal of PLF ear in an attempt to enhance the inner ear uptake of Gd-DTPA-BMA. The immediate loading of Gd-DTPA-BMA in the scala tympani of the basal turn was ablated by the outflow of perilymph through the leaking RWM while the oval window passage for Gd-DTPA-BMA was enhanced. There was more Gd-DTPA-BMA distribution in the scala tympani than in the scala vestibuli in the second turn of the PLF cochlea (within 20 min). Signal in the vestibulum and scala vestibuli of the basal turn and rest part of PLF cochlea was greater than that of the control cochlea with intact RWM within 30 min. Pressure applied to the external ear canal tended to enhance the loading of Gd-DTPA-BMA in the perilymphatic scalae of the PLF cochlea. The enhanced oval window passage of Gd-DTPA-BMA was proven by the distorted distribution in the inner ear with PLF. The radial communication of cochlear perilymph was supported by the Gd-DTPA-BMA gradient among the perilymphatic scalae. Applying positive pressure to the external ear canal caused backflow of perilymph into the cochlea which has a potential of transmitting microbes from the middle ear into the inner ear.

Effect of contrast agent on the results of in vivo1H MRS of breast tumors – is it clinically significant?

Choline (Cho) signal identification and quantification in (1)H MRS are used in breast cancer diagnosis. However, an influence of the gadolinium-based contrast agent on the Cho amplitude has been reported experimentally. This study aims to identify the impact of gadolinium-based contrast agents on Cho detection and quantification in postcontrast breast MRS. Consecutive patients were recruited prospectively and randomly allocated to two groups. Group A received a neutral (gadolinium diethylenetriaminepentaacetic acid bis-methylamide) and group B an ionic (gadolinium diethylenetriaminepentaacetic acid) contrast agent, each at a dosage of 0.1 mmol/kg. First, the presence of Cho was identified visually. Then, the normalized Cho intensity in malignant lesions was quantified. Multivariate analysis was applied to identify independent influencing factors on Cho. Sixty-three lesions were investigated [A, n = 34; B, n = 29; 43 malignant (one bilaterally malignant), 20 benign]. Cho was identified visually in 14 of 20 malignant tumors in group A and 12 of 22 malignant tumors in group B (p = 0.477). Normalized Cho differed significantly (p = 0.001) between groups A (mean, 26.8 ± 6.0 AU) and B (mean, 18.2 ± 12.5 AU). No linewidth differences were identified (p > 0.05). Multivariate analysis revealed only group membership (A versus B) as an independent predictor of Cho (p = 0.017). The results suggest stronger negative effects of an ionic relative to a neutral gadolinium-based contrast agent on breast tumor MRS in vivo. These results should be considered when conducting and comparing quantitative Cho measurements in the breast.

Imaging apolipoprotein AI in vivo.

Coronary disease risk increases inversely with high-density lipoprotein (HDL) level. The measurement of the biodistribution and clearance of HDL in vivo, however, has posed a technical challenge. This study presents an approach to the development of a lipoprotein MRI agent by linking gadolinium methanethiosulfonate (Gd[MTS-ADO3A]) to a selective cysteine mutation in position 55 of apo AI, the major protein of HDL. The contrast agent targets both liver and kidney, the sites of HDL catabolism, whereas the standard MRI contrast agent, gadolinium-diethylenetriaminepentaacetic acid-bismethylamide (GdDTPA-BMA, gadodiamide), enhances only the kidney image. Using a modified apolipoprotein AI to create an HDL contrast agent provides a new approach to investigate HDL biodistribution, metabolism and regulation in vivo.

Relationship between the Degree of Endolymphatic Hydrops and Electrocochleography

The purpose of this study was to evaluate the relationship between the endolymphatic space image obtained using magnetic resonance imaging (MRI) and the results of electrocochleography. Electrocochleography recordings were obtained from 25 ears of 24 patients, who underwent MRI 1 day after the intratympanic injection of gadolinium diethylenetriamine pentaacetic acid bismethylamide. The average summating potential to action potential (SP/AP) ratio in patients with significant endolymphatic hydrops in the cochlea was 54 ± 17%. However, in some patients who had significant endolymphatic hydrops in the cochlea, the SP/AP ratio was not enlarged. This may imply that elevation of the SP/AP ratio is related to not only the degree of endolymphatic hydrops but also to the persistence of hydrops.

Induction of the expression of profibrotic cytokines and growth factors in normal human peripheral blood monocytes by gadolinium contrast agents

Nephrogenic systemic fibrosis (NSF) is a severe fibrosing disorder occurring in patients with renal insufficiency. The majority of patients with this disorder have documented exposure to magnetic resonance imaging contrast agents containing Gd. The purpose of this study was to examine the effects of gadolinium diethylenetriaminepentaacetic acid bismethylamide (Gd[DTPA-BMA]; Omniscan) as compared with Gd-DTPA and GdCl3 on the expression and production of cytokines and growth factors by normal human peripheral blood monocytes in vitro and to examine whether conditioned media from Gd-exposed peripheral blood monocytes could induce a profibrotic phenotype in dermal fibroblasts. Normal human peripheral blood monocytes isolated by Ficoll-Hypaque gradient centrifugation and plastic adherence were incubated with various concentrations of Gd[DTPA-BMA], Gd-DTPA, or GdCl3. Gene expression of interleukins 4, 6, and 13, interferon-gamma, tumor necrosis factor alpha, transforming growth factor beta, connective tissue growth factor, and vascular endothelial growth factor were assessed by real-time polymerase chain reaction (PCR) analysis. Production and secretion of cytokines and growth factors by Gd compound-exposed monocytes was quantified by enzyme-linked immunosorbent assay proteome multiplex arrays. The effects of conditioned media from the Gd compound-exposed monocytes on the phenotype of normal human dermal fibroblasts were examined by real-time PCR and Western blotting. The 3 Gd-containing compounds stimulated the expression and production of numerous cytokines and growth factors by normal human peripheral blood monocytes. Conditioned media from these cells induced a profibrotic phenotype in normal human dermal fibroblasts. The 3 Gd-containing compounds studied induce potent cellular responses in normal human peripheral blood monocytes, which may participate in the development of tissue fibrosis in NSF.

Detection of apoptotic cell death in vitro in the presence of Gd‐DTPA‐BMA

Due to variability in patient response to cancer therapy, there is a growing interest in monitoring patient progress during treatment. Apoptotic cell death is one early marker of tumor response to treatment. Using known extracellular concentrations of gadolinium diethylenetriamine pentaacetic acid bismethylamide (Gd-DTPA-BMA) to vary the exchange regime, T(1) and T(2) relaxation data for acute myeloid leukemia (AML) cell samples were obtained and then analyzed using a two-pool model of relaxation with exchange. Leukemia cells treated with cisplatin to induce apoptosis exhibited a statistically significant (P < 0.05) decrease in intracellular longitudinal relaxation time, T(1I), from 1030 ms to 940 ms, a decrease (P < 0.001) in the intracellular water fraction, M(0I), from 0.86 to 0.68 and a statistically significant increase (P < 0.01) in transmembrane water exchange rate, k(IE), from 1.4 s(-1) to 6.8 s(-1). The changes in MR parameters correlated with quantitative histology, such as cellular cross-sectional area and average nuclear area measurements. The results of this study emphasize the importance of accounting for water exchange in dynamic contrast-enhanced MRI (DCE-MRI) studies, particularly those that examine tumor response to therapies in which apoptotic changes occur.

In vivoMRI visualization of endolymphatic hydrops induced by keyhole limpet hemocyanin round window immunization

Endolymphatic hydrops is considered one of the principal pathological manifestations of Meniere's disease and abnormal immunoreaction may be one of the aetiologies of the disease. To investigate the effect of keyhole limpet hemocyanin (KLH) immunization on cochlear morphology and function in vivo, guinea pigs were inoculated with KLH systemically and received round window membrane delivery (group I). In the control group (group II), KLH was replaced with phosphate buffered saline. In vivo gadolinium diethylenetriaminepentaacetic acidbismethylamide MRI was obtained and compound action potentials were measured. In MRI, evident endolymphatic hydrops was detected in 2 of the 4 animals in group I and blood-endolymph barrier permeability increased in 3 of the 4 animals. The membranous lateral wall and the spiral lamina, in continuation with the organ of Corti, were also demonstrated in the MRI. More than 10 dB hearing loss was found in 2 out of the 4 animals in group I. Neither endolymphatic hydrops nor blood-e...

Shoulder MR arthrography: In vitro determination of optimal gadolinium dilution as a function of field strength

To find the optimal contrast agent dilution to maximize signal intensity (SI), signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) in shoulder MR arthrography using MR systems operating at different magnetic field strengths. Autoptic human glenohumeral ligaments were inserted in eight egg-shaped 20-mL phantoms filled with saline and gadolinium diethylenetriaminepentaacetic acid bismethylamide (Gd-DTPA-BMA) in different dilutions of 0.5, 1, 2, 2.5, 5, 12.5, 50 mmol/liter, to simulate the shoulder articular capsule. These phantoms were inserted inside two plastic 240-mL phantoms filled with water. MRI was performed on 0.2-, 0.5-, 1.0-, 1.5-, and 3.0-T MR systems using a three-dimensional gradient echo (GRE)-T1-weighted pulse sequence. SI, SNR, and CNR were determined. Peak SI and SNR were found at 5 mmol/liter, with the exception of the 0.2-T scanner, where the maximum was at 2 mmol/liter. Peak CNR was observed at 1 mmol/liter for the 3-T scanner, at 2 mmol/liter for the 0.2- and 0.5-T scanners, and at 5 mmol/liter for the remaining scanners. The optimal SI and SNR are provided by 5 mmol/liter contrast agent dilution. Peak CNR was found in a range between 1 and 5 mmol/liter dilutions, depending on the strength of the magnetic field.

Influence of Severity of Myocardial Injury on Distribution of Macromolecules: Extravascular Versus Intravascular Gadolinium-Based Magnetic Resonance Contrast Agents

Objectives. This study sought to 1) compare the distribution of extravascular (573 Da) and intravascular (92 kDa) magnetic resonance (MR) contrast agents in reperfused infarcted myocardium, and 2) investigate the effect of injury severity on these distribution patterns.Background. Myocardial distribution of low and high molecular weight contrast agents depends on vascular permeability, diffusive/convective transport within the interstitium and accessibility of the intracellular compartment (cellular integrity).Methods. To vary the severity of myocardial injury, 72 rats were subjected to 20, 30, 45 or 75 min (n = 18, respectively) of coronary artery occlusion. After 2 h of reflow, the animals received either 0.05 mmol/kg of gadolinium-diethylenetriaminepentaacetic acid-bismethylamide (Gd-DTPA-BMA) (n = 24), (Gd-DTPA)30-albumin (n = 24) or saline (control group, n = 24). Three minutes after injection, the hearts were excised and imaged (spin-echo imaging parameters: repetition time 300 ms, echo time 8 ms, 2-tesla system), followed by triphenyltetrazolium chloride staining for infarct detection and sizing.Results. Histomorphometric and MR infarct size (expressed as percent of slice surface) correlated well: r = 0.96 for Gd-DTPA-BMA; r = 0.95 for (Gd-DTPA)30-albumin. On Gd-DTPA-BMA–enhanced images, reperfused myocardial infarctions were homogeneously enhanced. The ratio of signal intensity of infarcted/normal myocardium increased with increasing duration of ischemia (overall p < 0.0001, analysis of variance [ANOVA]), indicating an increase in the distribution volume of Gd-DTPA-BMA in postischemic myocardium. On (Gd-DTPA)30-albumin–enhanced images, reperfused infarctions consisted of a bright border zone and a less enhanced central core. The extent of the core increased with increasing duration of ischemia (overall p value < 0.0001, ANOVA).Conclusions. At 2 h of reperfusion, the distribution of MR contrast agents in postischemic myocardium is 1) specific for extravascular and intravascular agents, and 2) modulated by the duration of ischemia.

Occlusive and reperfused myocardial infarcts: MR imaging differentiation with nonionic Gd-DTPA-BMA.

To increase the time during which effective contrast exists between normal and infarcted myocardium, a high dose (0.6 mmol/kg) of the nonionic contrast medium gadolinium diethylenetriaminepentaacetic acid bismethylamide (Gd-DTPA-BMA) was used to distinguish between occlusive and reperfused myocardial infarctions in rats. After administration of Gd-DTPA-BMA, there was clear and persistent demarcation of both occlusive and reperfused infarcts on T1-weighted MR images. In occlusive infarcts, normal, infarcted, and periinfarcted myocardium could be identified. High signal intensity was evident for 60 minutes in a band straddling the border between infarcted and normal myocardium, namely, the periinfarction zone. In the reperfused infarct, normal and infarcted myocardium could be identified. The reperfused zone was immediately enhanced after injection of Gd-DTPA-BMA. A differential pattern of enhancement between occlusive and reperfused myocardial infarcts was evident for 1 hour. Thus, Gd-DTPA-BMA has the potential to allow (a) depiction of occlusive and reperfused acute myocardial infarcts, (b) documentation of reperfusion of myocardial infarction, and (c) distinction between occlusive and reperfused infarction.