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A Mühler

Publications and source records attributed to A Mühler.

At least 19 recordsLinked to original sources
PubMed2006

Evaluation of quantitative parametric analysis for characterization of breast lesions in contrast-enhanced MR mammography.

Our aim was to evaluate quantitative parametric analysis for characterization of breast lesions in contrast-enhanced magnetic resonance (MR) mammography. In 62 patients, contrast-enhanced MR mammography revealed 75 suspicious lesions, of which 18 were benign and 57 were malignant. The quantitative parametric analysis delineates signal intensity changes of contrast-enhanced lesions on a pixel-by-pixel basis. The initial rate of enhancement is coded by color intensity: a slow rate is coded to dark; a fast rate, bright. The postinitial enhancement change is coded by color hue: blue for increasing signal intensity, green for plateau, and red for decrease in signal intensity. Malignant lesions showed a significantly higher number of bright-red (P = 0.004) and medium-red (P < 0.001) pixels than benign lesions. Benign lesions showed significantly more blue pixels than did malignant lesions (P = 0.010). Of the 75 lesions, 72 (96%) showed heterogeneous distribution of pixel color hue. Quantitative parametric analysis of contrast kinetics in lesions can replace the subjective manual region of interest (ROI) method and makes a step toward standardization of MR mammography. It allows quantitative evaluation of different contrast kinetics parameters in contrast-enhanced breast lesions.

Adult↗
PubMed2000

Comparison of Gadomer-17 and gadopentetate dimeglumine for differentiation of benign from malignant breast tumors with MR imaging.

RATIONALE AND OBJECTIVES: This study compared gadopentetate dimeglumine (molecular weight, 0.5 kD), a standard contrast medium, and Gadomer-17 (apparent molecular weight, approximately 35 kD), a new, clinically applicable, large-molecular contrast medium, with respect to their microvascular characterizations of experimentally induced breast tumors at magnetic resonance (MR) imaging. MATERIALS AND METHODS: A spectrum of breast tumors, benign through highly malignant, was induced in Sprague-Dawley rats (n = 30) by intraperitoneal administration of N-ethyl-N-nitrosourea (ENU), a potent carcinogen. All animals underwent three-dimensional spoiled gradient-recalled MR imaging, with precontrast imaging and dynamic postcontrast imaging after injection of gadopentetate dimeglumine (0.1 mmol/kg) and Gadomer-17 (0.03 mmol/kg), administered in a random order at a 24-hour interval. Several microvascular parameters were compared: the endothelial transfer coefficient (K(PS)), a measure of microvascular permeability; the fractional plasma volume (fPV), and the plasma equivalent volume. Each MR imaging parameter was correlated with histopathologic findings. RESULTS: With Gadomer-17, the mean values for K(PS) and fPV were significantly greater in carcinomas than in fibroadenomas (P < .004 and .04, respectively). With gadopentetate dimeglumine, the mean values for fPV and PEV were significantly greater in carcinomas (P <. 004 and .02, respectively). Because of the high variability within both fibroadenoma and carcinoma groups, however, there were no significant correlations between K(PS), fPV, or PEV and histopathologic tumor grade as indicated by the Scarff-Bloom-Richardson score, for either agent. CONCLUSION: Although the K(PS) and fPV estimates obtained from dynamic MR imaging data with Gadomer-17 enhancement offer some potential for characterizing breast tumors, none of the quantitative microvascular parameters derived with either agent were significantly correlated with histopathologic tumor grade.

Animals↗
PubMed1999

Characterization of N-ethyl-N-nitrosourea-induced malignant and benign breast tumors in rats by using three MR contrast agents.

A carcinogen (N-ethyl-N-nitrosourea)-induced animal tumor model was established to grow malignant and benign breast tumors. In each tumor the pharmacokinetic characteristics were measured by using three contrast agents, gadolinium-diethylene-triamine-pentaacetic acid (Gd-DTPA; <1 kD), Gadomer-17 (35 kD), and albumin-Gd-DTPA (70-90 kD). Infiltrating ductal carcinomas (IDC) with low, medium, and high Scarf-Bloom-Richardson grades and fibroadenomas (FA) were analyzed. We found that Gd-DTPA could differentiate between FA and malignant tumors, but not between malignant tumors of low and high grades. In contrast, the intermediate size agent Gadomer-17 could differentiate between high-grade and low-grade IDC, but not between low-grade IDC and FA due to their similar enhancement patterns (despite their different origins). The largest agent, albumin-Gd-DTPA, was capable of differentiating both, but the low contrast-to-noise ratio was its major technical concern. The results in this breast tumor model suggest that macromolecular agents provide useful information for differential diagnosis among IDCs of various grades, but they do not provide superior information than Gd-DTPA for differential diagnosis between IDC and FA.

Albumins↗
PubMed1999

MRI of acute myocardial ischemia: comparing a new contrast agent, Gd-DTPA-24-cascade-polymer, with Gd-DTPA.

A new macromolecular contrast agent, gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA)-24-cascade-polymer, was compared with Gd-DTPA for time-dependent delineation of acute myocardial ischemia. Acute myocardial ischemia was produced in 12 rats by occluding the anterior branch of the left coronary artery for 20-40 minutes. Dynamic spin-echo magnetic resonance imaging (MRI) was performed for 30 minutes after injection of Gd-DTPA (n = 6) or the cascade polymer (n = 6) using equimolar doses (0.1 mmol of Gd/kg). The contrast agent-induced changes in signal intensity (deltaSI) in normal and ischemic myocardium were observed. In normal myocardium, both contrast agents caused a sharp increase in deltaSI, followed by a decline to baseline values over the 30-minute period. Enhancement in the ischemic myocardium was attenuated. Gd-DTPA showed greater deltaSI in ischemic myocardium than the cascade polymer, which gave rise to virtually no enhancement. Significant differences (P<0.05) in signal enhancement between normal and ischemic myocardium persisted for only 6 minutes using Gd-DTPA but for 18 minutes with the cascade polymer. Use of Gd-DTPA-24-cascade-polymer extends the temporal window of dynamic contrast-enhanced MRI for the differentiation of ischemic and normal myocardium. Identification of the ischemic zone is easier with the cascade polymer, which demonstrates virtually no signal enhancement in this territory.

Animals↗
PubMed1999

Contrast-enhanced MR imaging of two superparamagnetic RES-contrast agents: functional assessment of experimental radiation-induced liver injury.

The purpose of this study was to compare liver contrast-enhancing characteristics of two superparamagnetic reticuloendothelial system (RES)-directed agents with different particle sizes, polycrystalline iron oxide nanocompounds (PION) and carboxydextran-coated maghemite (DDM128N/389, later referred to as DDM128), in an experimental model of focal radiation-induced hepatitis. PION, for the small particle size (31 nm), and DDM128, for the large particle size (59 nm), RES-directed agents were compared for liver enhancement after radiation-induced liver injury. A single x-irradiation exposure varying from 10 to 60 Gy was delivered to one side of the liver. T2-weighted spinecho magnetic resonance imaging was performed 3 days after x-irradiation at 30 minutes post-contrast. Using the RES-directed PION, the normal, non-irradiated portion of the liver decreased in signal intensity with a maximum negative enhancement of -66%, while the irradiated portion of the liver decreased in signal intensity by -24% (60 Gy). The signal intensity decline of irradiated liver tissue using PION was dose dependent, but was found at all radiation dose levels (10-60 Gy). The difference in signal intensity between irradiated (-63%) and non-irradiated (-82%) portions was also statistically different using DDM128 at 60 Gy. However, lower irradiation doses (10 and 30 Gy) failed to produce a statistically significantly different enhancement in the irradiated and non-irradiated portion of the liver. Sensitivity of liver enhancement with RES-directed agents is size dependent. The smaller particle (PION) is more sensitive for detection of radiation-induced hepatitis than the larger particle (DDM128). The relative insensitivity of DDM128 enhancement for diffuse liver injury will be clinically advantageous for detecting focal lesions in the presence of diffuse hepatic injury.

Animals↗
PubMed1999

Does a higher concentration of gadolinium chelates improve first-pass cardiac signal changes?

The purpose of this study was to evaluate first-pass cardiac signal changes with a higher concentrated gadolinium-chelate (gadobutrol) and its influence on bolus geometry. Phantom studies and in vivo first-pass cardiac studies were performed in rabbits (n = 8 experiments) under general anesthesia at 1.0 T using an ultrafast T1-weighted Turbo-fast low-angle shot (FLASH) sequence (TR/TE 4.7/1. 6 msec, alpha = 90 degrees ) with a time resolution of 870 msec. Gadobutrol was injected as an intravenous bolus at two concentrations (0.5 and 1.0 mol Gd/L) and five doses (0.3, 0.15, 0.1, 0.055, and 0.03 mmol Gd/kg bw). The blood-pool gadolinium compound gadopentetate dimeglumine-polylysine (0.15, 0.075, 0.05, and 0.015 mmol Gd/kg bw, 0.5 mol Gd/L) and the standard extracellular gadopentetate dimeglumine (0.1 and 0.05 mmol Gd/kg bw, 0.5 mol Gd/L) served as reference agents. Cardiac signal changes were calculated from serial signal intensity measurements. Maximum signal intensity changes and best peak profiles during first pass of the right and left ventricle were observed with a dose of 0.03 mmol Gd/kg bw gadobutrol using T1-weighted Turbo-FLASH. At the low application volumes used, the higher concentration of 1.0 mol Gd/L gadobutrol did not increase the degree of signal intensity changes or sharpen the bolus profile. First-pass cardiac signal changes using T1-weighted Turbo-FLASH with the new extracellular contrast agent gadobutrol are best observed at a dose of 0.03 mmol Gd/kg bw. There is no advantage to the concentrated formulation (1 mol Gd/L gadobutrol) when using small injection volumes. J. Magn. Reson. Imaging 1999;10:806-812.

Animals↗
PubMed1998

Tumor characterization with dynamic contrast-enhanced MRI using MR contrast agents of various molecular weights.

Dynamic contrast-enhanced MR imaging was used to measure the kinetics of enhancement in three different animal tumor models (Walker 256, R3230 AC, MCF7) using three different Gd complexes (Gd-DTPA, Gd-DTPA-24-cascade-polymer 30 kD, and polylysine-Gd-DTPA 50 kD). The three tumor models varied in growth rate, with the most rapid growth demonstrated by Walker 256 cells and the slowest growth occurring in the MCF7 cells. For each tumor, the kinetics of enhancement using polylysine-Gd-DTPA was analyzed using a pharmacokinetic model to estimate the vascular volume of the tumor. The rate of entry of the contrast agent into the interstitial space served as the measure of vascular permeability. The smallest molecular-weight agent, Gd-DTPA, could not provide information about vascular permeability. The intermediate and the largest agents both demonstrated that the faster-growing Walker 256 tumor had greater vascular permeability than did the slower-growing R3230 AC tumor. The degree of vascular permeability in the MCF7 tumor could not be assessed fairly due to insufficient statistics. The current study provides evidence supporting the hypothesis that more rapidly growing tumors have higher vascular permeability than do tumors that grow more slowly.

Animals↗
PubMed1997

[Macromolecular contrast media for MR mammography. A new approach to characterizing breast tumors].

The value of macromolecular contrast agents (MMCM) for the characterization of benign and malignant breast tumors will be demonstrated in this review. Animal studies suggest a high potential of MMCM to increase the specificity of MR-mammography. The concept of tumor differentiation is based on the pathological hyperpermeability of microvessels in malignant tumors. MMCM show a leak into the interstitium of carcinomas, whereas they are confined to the intravascular space in benign tumors. Capabilities and limitations of the MMCM-prototype. Albumin-Gd-DTPA, for breast tumor characterization will be summarized and compared to the standard low molecular weight contrast agent Gd-DTPA. Initial experience with new MMCM, such as Dendrimers, Gd-DTPA-Polylysine and MS-325 will be outlined. The potential of "blood-pool"-iron oxides, such as AMI-227 for the evaluation of tumor microvascular permeabilities will be discussed.

Breast↗
PubMed1997

[Iron oxide contrast media improve the magnetic resonance imaging of the portal vein system--an animal experimental study].

PURPOSE: The aim was to demonstrate that intravenous superparamagnetic iron oxide contrast agents improve the delineation of the portal venous system. MATERIAL AND METHODS: The portal venous system of 8 minipigs was demonstrated by a FLASH 2-D MRA-sequence. Scans were acquired before and after intravenous administration of 10 and 20 mumol/kg of a superparamagnetic iron oxide contrast agent (SHU 555 A). Signal intensities were measured in the portal vein and hepatic parenchyma and contrast-to-noise ratios were calculated. RESULTS: Following a cumulative dose of 10 mumol iron oxide, hepatic parenchymal signal intensity decreased to 67 +/- 6%, following 20 mumol to 29 +/- 4%, and following 40 mumol to 13 +/- 2% of control (p < 0.0001). These effects improved the contrast-to-noise ratio of the portal vein (469 +/- 114%, 858 +/- 243%, and 957 +/- 272% of control in the left portal vein main branch, p = 0.02). CONCLUSION: A decrease in hepatic parenchymal signal due to a magnetic susceptibility effect accounts for an improvement of portal venous conspicuity following intravenous administration of iron oxide contrast medium.

Animals↗
PubMed1997

Hemodynamic tolerance of intravascular contrast agents for magnetic resonance imaging.

RATIONALE AND OBJECTIVES: Intravascular contrast agents for magnetic resonance imaging (MRI) facilitate the quantification of tissue perfusion. The authors determined the hemodynamic tolerance of these agents. METHODS: Doses of 0.05, 0.15, and 0.45 mmol/kg of the polymeric intravascular contrast agent gadolinium-DTPA-polylysine, and di-nitrobenzyl-gadolinium-DTPA, a non-polymeric intravascular contrast agent with high protein binding, and gadolinium-DTPA dimeglumine, a paramagnetic contrast agent with extracellular distribution, were injected into 18 normal male rats as a peripheral intravenous bolus. Systolic, diastolic, and mean blood pressure, left ventricular end-diastolic and developed pressure, positive rate of pressure change (+dP/dt), dP/dt, the rate-pressure product, and heart rate were recorded during a period of 20 minutes. Hemodynamic effects were established by analysis of variance for repeated measurements. RESULTS: There was a transient increase of all blood pressure parameters and contractility for Gd-DTPA-polylysine at the dose of 0.45 mmol/kg only. Di-nitrobenzyl-Gd-DTPA increased blood pressure parameters at 0.45 mmol/kg only. At doses of 0.05 and 0.15 mmol/kg, no significant hemodynamic effects were observed. CONCLUSIONS: The authors conclude that Gd-DTPA-polylysine is hemodynamically safe at doses to 0.15 mmol/kg and acts like a plasma expander at higher doses after peripheral bolus injection in normal rats. Additional investigations are indicated to elucidate the mechanism of a nonsignificant and satiable transient hemodynamic depression after injection of 0.05 mmol/kg DNB-Gd-DTPA.

Animals↗
PubMed1997

Magnetic resonance imaging of pulmonary ventilation. Initial experiences with a gadolinium-DTPA-based aerosol.

RATIONALE AND OBJECTIVES: The authors investigate whether a modified gadolinium (Gd)-DTPA formulation can be aerosolized and used as a contrast agent for magnetic resonance (MR) ventilation imaging of the lungs. METHODS: Gadolinium-DTPA (gadopentetate dimeglumine, Schering AG, Berlin, Germany, 100 mmol Gd/L) was modified by addition of mannitol (Sigma, Deisenhofen, Germany, 10 mg/mL) and the surface active detergent Lutrol F68 (BASF, Mannheim, Germany, 2 mg/mL). The imaging was performed in an anesthetized rat model after inhalation of the contrast agent aerosol (PulmoSonic, De Vilbiss, Germany, 10-minute nebulization). T1-weighted spin echo images (repetitive time [TR]/echo time [TE] = 40/3 mseconds) were acquired at 2 T (SIS 85; Sisco, Fremont, CA) before and as long as 120 minutes after administration of the contrast agent. RESULTS: The modified Gd-DTPA aerosol elicited high and relatively homogeneous enhancement of the lung directly after nebulization. The enhancement was more pronounced than that obtained with a Gd-DTPA formulation without additives. CONCLUSIONS: Gadolinium-DTPA-based aerosol appears to be a suitable contrast agent for MR ventilation imaging in an experimental animal model. Modification by mannitol (to increase proton density through a slight additional osmotic effect) and a detergent (to reduce droplet size by decreasing surface tension) is suitable and effective in increasing signal intensity compared with Gd-DTPA without modification.

Administration, Inhalation↗
PubMed1997

Definition of liver tumors in the presence of diffuse liver disease: comparison of findings at MR imaging with positive and negative contrast agents.

PURPOSE: The potential to define liver tumors at magnetic resonance (MR) imaging was compared with a positive and a negative contrast agent (gadoxetic acid disodium, or gadolinium EOB-DTPA [a hepatocyte-directed agent], and ferumoxides, or superpara-magnetic iron oxide particles [a Kupffer cell-directed agent], respectively) in normal rats and in rats with induced acute hepatitis, fatty liver, or cirrhosis. MATERIALS AND METHODS: Rats with implanted liver adenocarcinomas were divided into four groups: no diffuse liver disease ("normal" [n = 6]) and diffuse liver diseases (induced acute hepatitis [n = 6], fatty liver [n = 6], or cirrhosis [n = 6]). Rats first received gadoxetic acid disodium (50 mumol/kg) and then, 45 minutes later, ferumoxides (10 mumol/kg). Liver signal intensity enhancement and tumor-to-liver contrast-to-noise ratio (C/N) were measured in each group. RESULTS: Mean liver signal intensity enhancement values with gadoxetic acid disodium and ferumoxides were excellent in the normal liver model (176% and -62%, respectively; P < .01) but were significantly reduced in the acute hepatitis model (82% and -36%, respectively). In the fatty livers compared with the normal livers, enhancement with gadoxetic acid disodium was reduced (57%) but with ferumoxides was excellent (-55%). In the cirrhotic livers compared with the normal livers, enhancement with gadoxetic acid disodium (174%) was virtually the same but was impaired with ferumoxides (-43%). CONCLUSION: Hepatic enhancement and tumor-to-liver C/N with either positive or negative liver-enhancing agents can be impaired by the presence of underlying liver disease. Prior knowledge of the type of diffuse liver disease may influence the choice of contrast agent for tumor detection.

Acute Disease↗
PubMed1996

[Experimental evaluation of contrast medium enhanced high resolution MR angiography in the animal model. Gd-DTPA compared with Gd-DTPA-polylysine].

PURPOSE: To evaluate the qualitative and quantitative efficacy of Gd-DTPA and Gd-DTPA polylysine for contrast-enhanced high resolution MRA (CMRA) of the abdominal vessels. MATERIALS AND METHODS: In ten anesthesized rabbits (average weight 4.3 kg) MR angiography was performed using a 1.5 T MR unit (Magnetom SP 63; Siemens Erlangen) and a CP head coil. Arterial MRA (FISP 3D TONE, TR/TE = 33/8, Flip 20 degrees) and venous MRA (FLASH 2D, TR/TE = 37/10, Flip 60 degrees) was performed before and after administration of the paramagnetic contrast agents Gd-DTPA (n = 5) or Gd-DTPA polylysine (n = 5) at a dosage of 0.1 mmol/kg. In all studies the single sections and the MIP reconstructions were evaluated quantitatively by measuring and calculating signal intensity, percentage enhancement, signal-to-noise and contrast-to-noise ratios. All studies were assessed qualitatively for visualization and distinction of the arterial and venous vessel system by three independent observers before and after the administration of contrast agent. RESULTS: Gd-DTPA-enhanced arterial FISP 3D tone led to a percentage enhancement of 30% for the kidneys, 12% for the superior mesenteric artery, 18% for the deep circumfluent iliac artery, and 7% for the internal iliac artery. In FLASH 2D sequences Gd-DTPA led to a good C/N only for venous abdominal vessels like the left renal vein (2.59) and internal iliac vein (1.66); the percentage enhancement of these structures was between 16 and 21%. Qualitative comparison also showed no significant improvement after injection of Gd-DTPA. In FISP 3D TONE sequences Gd-DTPA polylysine led to a strong percentage enhancement of right and left kidney (21 and 40%) and deep circumfluent iliac artery (17%). Qualitative evaluation showed improved delineation and contrast of low-diameter vessels, while the soft tissue was only slightly enhanced and did not impair vessel visualization. CONCLUSION: CMRA using Gd-DTPA and Gd-DTPA polylysine significantly improved the delineation of abdominal vessels, with Gd-DTPA polylysine being superior.

Abdomen↗
PubMed1996

Approximation of arterial input curve data in MRI estimation of cerebral blood-tumor-barrier leakage: comparison between Gd-DTPA and 99mTc-DTPA input curves.

Accurate and reproducible MRI measurements of the blood-brain-barrier transport rate constant Ki require measurements of the arterial Gd-DTPA concentration to characterise the arterial input function to the brain. Methods of measuring [Gd] in human plasma are not common practice in clinical departments. In this study we present a fast and easy method of substituting Gd-DTPA with 99mTc-DTPA as the 'tracer' to be measured for the characterisation of the arterial input curve in MRI blood-brain-barrier (BBB) measurements. Gd-DTPA and 99mTc-DTPA was injected intravenously as a bolus into six brain tumor patients during dynamic, fast gradient-echo MRI. Arterial blood samples were collected with an interval of 10(5) during imaging. 99mTc-DTPA and Gd-DTPA were measured in the same blood samples by scintillation counting and Inductively Coupled Plasma Atomic Emission Spectroscopy respectively. The two methods yield the concentrations of both the tracers in mmol/l Gd-DTPA and hence the results are directly comparable. The data results showed no statistically significant difference between the two methods. However, the 99mTc-DTPA method had fewer 'bad points' than the direct Gd-DTPA measurement method. The input curves were in agreement. Conclusively, we found that Gd-DTPA and 99mTc-DTPA were equivalent with regard to distribution and elimination-kinetics during the first 10 min after administration and, therefore, characterisation of arterial input curves may be done using simultaneous injection of 99mTc-DTPA and Gd-DTPA in facilities where means of measuring Gd-DTPA is not available.

Adenocarcinoma↗