PubMed Health⌕ Search

Biomedical subjects

A Mühler

Publications and source records attributed to A Mühler.

66 records · Page 4Linked to original sources

Detection of zonal renal ischemia with contrast-enhanced MR imaging with a macromolecular blood pool contrast agent.

The potential of magnetic resonance (MR) imaging enhanced with albumin-(gadolinium diethylenetriaminepentaacetic acid [DTPA])35, a macromolecular blood pool marker, for detection of focal changes in renal perfusion was studied in a myoglobinuric acute renal failure (ARF) model in the rat. T1-weighted spin-echo postcontrast images of injured kidneys at 3 hours after glycerol injection showed three distinct zones: a strongly enhanced outer cortex, a low-intensity inner cortex, and a strongly enhanced medulla. The distinct band of low intensity in the inner cortex indicated zonal decreased blood volume, corresponding to published microsphere data showing zonal low perfusion in the inner cortex. Contrast differences between parenchymal zones were significant for at least 30 minutes. No focal ischemic changes could be delineated on nonenhanced images. Enhanced and nonenhanced images of injured kidneys obtained at 24 hours after glycerol injection revealed no zonal differentiation. Contrast-enhanced MR imaging data in this ARF model correlated well with pathologic data and microsphere perfusion results. Contrast-enhanced characterization of the ischemic phase of renal injury with MR imaging may improve specificity for the diagnosis of ARF and may serve as a marker for therapeutic intervention.

Albumins↗

Comparison of Gd-EOB-DTPA and Gd-DTPA for contrast-enhanced MR imaging of liver tumors.

A new hepatobiliary contrast agent for magnetic resonance (MR) imaging, gadolinium-ethoxybenzyl (EOB)-diethylemetriaminepentaacetic acid (DTPA), was compared with Gd-DTPA to define the potential for improving tumor-liver contrast in a rodent liver adenocarcinoma model. With a T1-weighted spin-echo sequence, the contrast-to-noise ratio (C/N) for tumor before contrast agent administration was 5 (arbitrary units), the tumor appearing slightly hypo-intense with respect to liver parenchyma. After Gd-DTPA injection (0.1 mmol/kg), tumor enhanced more strongly than liver, resulting in an equalization of tumor and liver signal intensities and a decline in C/N to zero at 3 minutes after injection. After Gd-EOB-DTPA injection (0.1 mmol/kg), liver enhanced more strongly than tumor. Five minutes after injection, C/N increased from 5 to 25 and remained above 17 for 50 minutes. The data indicate that Gd-EOB-DTPA yields higher and more prolonged tumor-liver contrast than Gd-DTPA on T1-weighted spin-echo images. The high liver-tumor contrast after Gd-EOB-DTPA administration should prove clinically advantageous for MR imaging detection of focal hepatic masses.

Animals↗

Safety aspects and pharmacokinetics of inhaled aerosolized gadolinium.

This study evaluated the pharmacokinetics and potential toxicity of inhaled aerosolized gadopentetate dimeglumine. The pharmacokinetics were evaluated with in vitro relaxometry of the lungs, blood, urine, and liver before and for up to 36 hours after a 5-minute inhalation of aerosolized gadopentetate dimeglumine (0.25 mol/L). For assessment of potential toxicity, hemodynamic variables were monitored during and for 10 minutes after inhalation. Extravascular lung water was measured before and after exposure. Finally, the potential for tissue damage was evaluated histologically. Pulmonary clearance of aerosolized gadopentetate dimeglumine was monoexponential with a half-time of 2.16 hours. Aerosolized gadopentetate dimeglumine was excreted through the kidneys, as shown by the decrease in urinary T1. Renal elimination was completed by 30 hours. No acute hemodynamic effect, histologic change, or induction of edema was demonstrated. This study shows that inhalation of aerosolized gadopentetate dimeglumine is well tolerated in rats and favors the further evaluation of this administration route, including clinical trials.

Aerosols↗

MR imaging of blood oxygenation-dependent changes in focal renal ischemia and transplanted liver tumor in rat.

The potential of using fast magnetic resonance (MR) imaging in conjunction with apnea-induced blood deoxygenation for the noninvasive monitoring of relative perfusion in the rat abdomen has been studied with two experimental models: glycerol-induced focal renal ischemia and transplanted liver tumor. Gradient-echo echo-planar imaging (GRE-EPI) (TE of 20 msec at 2T) of liver and kidney was performed before, during, and after a 60-second apnea episode and then was followed in the same rat by contrast-enhanced (a) GRE-EPI and (b) T1-weighted spin-echo imaging (TR msec/TE msec = 200/6) with polylysine-(gadolinium-DTPA [diethylenetriaminepentaacetic acid]). The results indicate that a noninvasive vascular challenge due to apnea can be used for the detection of focal tissue perfusion abnormalities in rat kidney and liver tumor.

Animals↗

Prolonged positive contrast enhancement with Gd-EOB-DTPA in experimental liver tumors: potential value in tissue characterization.

To evaluate the potential of the hepatobiliary magnetic resonance (MR) imaging contrast agent gadolinium EOB-DTPA (ethoxybenzyl diethylenetriaminepentaacetic acid) for the characterization of hepatic tumors, 79 primary and six implanted hepatomas in 38 rats were studied. MR imaging findings after administration of Gd-DTPA (0.3 mmol/kg) and Gd-EOB-DTPA (30 mumol/kg) were correlated with microangiographic and histologic findings. Gd-EOB-DTPA produced a strong liver enhancement, which caused prompt negative contrast enhancement (CE) in all implanted hepatomas and in 77 of 79 primary hepatomas. A positive CE that lasted up to 2 hours was found in two of 79 primary hepatomas, both of which were highly differentiated (grade I) hepatocellular carcinomas (HCCs). The rest were moderately differentiated to undifferentiated HCCs (grades II-IV). Rim enhancement, which corresponded histologically to peritumoral malignant infiltration sequestering normal hepatocytes, was seen around all implanted and some primary hepatomas. Positive tumor CE after administration of Gd-EOB-DTPA in this study is much less frequent but much more specific in comparison with the results of previous studies with manganese-DPDP (N,N'-dipyridoxylethylenediamine-N,N'-diacetate 5,5'-bis[phosphate]). These findings may help further discriminate hepatic tumors.

Animals↗

Gd-DTPA-cascade-polymer: potential blood pool contrast agent for MR imaging.

Gadolinium-DTPA (diethylenetriaminepentaacetic acid)-cascade-polymer, a potential new blood pool contrast agent for magnetic resonance (MR) imaging, was compared with a known blood pool agent, Gd-DTPA-polylysine, in an animal model. The relative signal intensities of liver, renal cortex, pancreas, and trunk muscle were assessed in 12 pigs between 4 seconds and 120 minutes after injection of a 20 mumol/kg dose of each contrast agent, by using a FLASH (fast low-angle shot) sequence. Except for muscle, all tissues showed visible enhancement after injection of either contrast agent. After injection of Gd-DTPA-polymer, enhancement patterns in the liver, renal cortex, and pancreas were similar to those seen after injection of Gd-DTPA-polylysine. No statistically significant differences in enhancement between the two contrast agents were found at any time point. The authors conclude that the contrast kinetics of Gd-DTPA-cascade-polymer are similar to those of Gd-DTPA-polylysine and that this agent may also be used as a blood pool contrast agent for MR imaging.

Animals↗

Characterization of a gadolinium-labeled cholesterol derivative as an organ-specific contrast agent for adrenal MR imaging.

The purpose of the study was to determine if derivatization of cholesterol with a paramagnetic label could result in an organ-specific contrast agent for magnetic resonance imaging of the adrenal glands. Gadolinium-DO3A-labeled cholesterol was synthesized and the relaxivities in water and blood plasma determined at 0.47 T and 40 degrees C. Organ distribution was measured at 2 (n = 2) and 24 (n = 2) hours after intravenous injection of a 50 mumol/kg dose of Gd-DO3A-cholesterol in rats weighing 220-240 g. T1-weighted spin-echo images were acquired at 2 T before and after injection of 50 mumol/kg Gd-DO3A-cholesterol (n = 2) and Gd-DTPA (diethylenetriaminepentaacetic acid)-albumin (n = 2). More than 99% of the Gd-DO3A-cholesterol was found to be protein bound in bovine serum. High T1 and T2 relaxivities were found in water and plasma. High tissue concentrations of Gd-DO3A-cholesterol were found only in adrenal glands and liver. At 24 hours, adrenal gadolinium concentrations were about 10 times higher than in blood. At 2 hours after injection of Gd-DO3A-cholesterol, enhancement was 162% in adrenal glands and 146% in liver. With Gd-DTPA-albumin, enhancement values were 57% and 56%, respectively.

Adrenal Glands↗

Regional myocardial blood volume and flow: first-pass MR imaging with polylysine-Gd-DTPA.

The authors investigated the utility of an intravascular magnetic resonance (MR) contrast agent, poly-L-lysine-gadolinium diethylenetriaminepentaacetic acid (DTPA), for differentiating acutely ischemic from normally perfused myocardium with first-pass MR imaging. Hypoperfused regions, identified with microspheres, on the first-pass images displayed significantly decreased signal intensities compared with normally perfused myocardium (P < .0007). Estimates of regional myocardial blood content, obtained by measuring the ratio of areas under the signal intensity-versus-time curves in tissue regions and the left ventricular chamber, averaged 0.12 mL/g +/- 0.04 (n = 35), compared with a value of 0.11 mL/g +/- 0.05 measured with radiolabeled albumin in the same tissue regions. To obtain MR estimates of regional myocardial blood flow, in situ calibration curves were used to transform first-pass intensity-time curves into content-time curves for analysis with a multiple-pathway, axially distributed model. Flow estimates, obtained by automated parameter optimization, averaged 1.2 mL/min/g +/- 0.5 (n = 29), compared with 1.3 mL/min/g +/- 0.3 obtained with tracer microspheres in the same tissue specimens at the same time. The results represent a combination of T1-weighted first-pass imaging, intravascular relaxation agents, and a spatially distributed perfusion model to obtain absolute regional myocardial blood flow and volume.

Animals↗

Evaluation of portal MR angiography using superparamagnetic iron oxide.

The purpose of our research was to determine the effects of superparamagnetic iron oxide on MR imaging of the portal venous system. Eight piglets were examined in deep anaesthesia and respiratory arrest using a time-of-flight magnetic resonance fast low angle shot, two-dimensional angiography sequence at 1.5T, MR angiograms were acquired precontrast and after intravenous administration of a cumulative dose of 10, 20 and 40 mumol/kg SHU 555A, a superparamagnetic iron oxide contrast agent for MR imaging with a particle size of 60 nm. For each dose, two subsequent sets of scans were obtained and reconstructed by a maximum-intensity-projection algorithm. Hepatic parenchymal and portal venous signal intensities were measured, and portal vein contrast calculated for each set of scans. All examinations were visually rated as to portal vein contrast and homogeneity by two blinded observers. Receiver operating characteristics of both observers were analyzed. The contrast agent reduced hepatic parenchymal signal in a dose-dependent way. After a cumulative dose of 10 mumol iron oxide, hepatic parenchymal signal intensity decreased to 63 +/- 6% (average of measurements at 4 and 14 minutes, mean +/- standard error of the mean), after 20 mumol to 24 +/- 3%, and after 40 mumol to 12 +/- 1% of control. Intravascular signal in the left main portal vein branch increased to 117 +/- 6%, 127 +/- 10%, and 133 +/- 9% of control, respectively. The contrast-to-noise ratio of the portal vein improved (521 +/- 90%, 891 +/- 178%, and 995 +/- 201% of control in the left portal vein main branch). Intravascular signal intensities increased slightly. The combined effect improved contrast of the portal vein stem and its branches. Receiver operating characteristics analysis documented dose-dependency of contrast medium effects on portal venous contrast and intravascular homogeneity. Visual rating also indicated a positive effect on portal venous contrast. The superparamagnetic iron oxide agent improved portal venous contrast with surrounding hepatic parenchyma in this normal animal model, and could potentially result in more accurate diagnosis of portal venous pathology.

Animals↗

Comparison of albumin-(Gd-DTPA)30 and Gd-DTPA-24-cascade-polymer for measurements of normal and abnormal microvascular permeability.

The purpose of this study was to compare a new MR macromolecular contrast medium (MMCM), gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA)-24-cascade-polymer, to a well-studied prototype MMCM, for the potential of distinguishing tissues of varying endothelial permeability. Three tissue models of varying capillary permeability were studied in a total of 46 rats: normal myocardium (normal capillaries), subcutaneously implanted adenocarcinoma (mild capillary leak), and reperfused infarcted myocardium (high capillary leak). TI-weighted MRI was performed before and dynamically after injection of either albumin-(Gd-DTPA)30 or the cascade polymer (each .02 mmol gadolinium [Gd] per kg). Data analysis based on a two-compartment kinetic model yielded estimates of fractional blood volume (BV) (percentage) and fractional leak rate (FLR) (1 per hour). Permeability to the cascade polymer as reflected in FLR was considerable in normal myocardium (8.24 per hour), of similar value in tumors (8.55 per hour), but significantly greater in infarcted myocardium (39.17 per hour, P < .01) versus normal myocardium. The larger albumin-(Gd-DTPA)30 demonstrated minimal extravasation in normal myocardium (FLR .33 per hour); FLR in tumors was 100% higher (.66 per hour, P < .002) and FLR in reperfused capillaries was significantly greater (7.94 per hour, P < .001). Based on capillary permeability measurements, the cascade polymer may have limited utility for detection of mildly increased microvascular permeabilities. For severe tissue injury, the cascade polymer can resolve abnormal microvascular integrity.

Analysis of Variance↗

Dynamic MRI of a hypovascularized liver tumor model: comparison of a new blood pool contrast agent (24-gadolinium-DTPA-cascade-polymer) with gadopentetate dimeglumine.

We evaluated the enhancement properties of a new blood pool contrast agent (24-gadolinium-diethylenetriamine pentaacetic acid [Gd-DTPA]-cascade-polymer) in comparison with gadopentetate dimeglumine in 24 rabbits with an experimentally induced VX-2 liver tumor. Dynamic MRI of the liver was performed before, immediately after, and within 15 seconds to 30 minutes after contrast agent administration. Relative signal intensities and contrast-to-noise ratios (CNRs) of both agents were evaluated. After blood pool agent administration a significantly higher CNR between liver and tumor was observed within 2 to 30 minutes after injection as compared with the CNR after gadopentetate dimeglumine. Within 4 to 30 minutes after injection of gadopentetate dimeglumine, the relative signal intensities of tumor were significantly higher than after administration of the blood pool agent. In conclusion, the new blood pool contrast agent demonstrated a significantly better CNR of the experimental hypovascularized liver tumor than gadopentetate dimeglumine.

Animals↗