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Biomedical subjects

A Mühler

Publications and source records attributed to A Mühler.

At least 37 records · Page 2Linked to original sources

[MRT of experimental liver abscesses: a comparison of a new blood pool contrast medium with gadolinium-DTPA in animal experiments].

PURPOSE: In an experimental pyogenic liver abscess model, the signal intensities were compared intraindividually and interindividually after the application of a new blood pool contrast agent, 24-gadolinium-DTPA (diethylenetriamine-pentaacetic acid) cascade polymer, and after the application of gadopentetate dimeglumine. METHODS: In 20 rabbits with experimentally induced liver abscesses, the relative signal intensities of the liver, abscess centre, abscess wall and portal vein were assessed before and between 30 seconds and 60 minutes after injection of a 25 mumol/kg dose of gadolinium polymer and of 100 mumol/kg of gadolinium-DTPA, respectively. Measurements were performed at 1.5 Tesla, using a head coil and a Flash-2-D sequence. RESULTS: The interindividual comparison (unpaired T-test, p < 0.05) yielded significant differences of the relative signal intensities of the abscess centre (at any time point after contrast-media application), abscess wall (between 15 and 60 minutes after contrast media application), and portal vein (between 30 seconds and 7.5 minutes after contrast media application). The interindividual comparison showed a significantly higher abscess centre-liver contrast (between 30 seconds and 12.5 minutes after contrast media application) and a significantly higher abscess wall-centre contrast (between two and 7.5 minutes after contrast media application) after the application of gadolinium polymer compared with gadopentetate dimeglumine. CONCLUSION: In this animal model, the higher abscess centre-liver contrast after the application of gadolinium polymer was the basis for a better and prolonged visibility of the abscesses, as compared with images acquired after injection of gadopentetate dimeglumine.

Animals↗

Functional hepatobiliary imaging with gadolinium-EOB-DTPA. A comparison of magnetic resonance imaging and 153gadolinium-EOB-DTPA scintigraphy in rats.

RATIONALE AND OBJECTIVES: Gadolinium-EOB-DTPA (Gd-EOB-DTPA) is a hepatobiliary magnetic resonance (MR) imaging contrast medium designed to detect focal liver lesions. The objective of this study was to evaluate dynamic Gd-EOB-DTPA-enhanced MR imaging as a new method for assessing liver excretory function and to compare it with a scintigraphic method, the gold standard. METHODS: Changes in scintigraphic liver activity or MR liver signal intensity were intraindividually monitored over time after intravenous injection of 50 mumol Gd/kg of Gd-EOB-DTPA in controls and rats with common bile duct obstruction or L-ethionine-induced fatty liver (n = 6). RESULTS: A comparison of liver scintigraphy and MR imaging revealed that elimination half-lives of Gd-EOB-DTPA were significantly longer in rats with common bile duct obstruction (scintigraphy: 100 +/- 27 minutes; MR imaging: 59 +/- 18 minutes) or fatty liver (scintigraphy: 94 +/- 30 minutes; MR imaging: 72 +/- 32 minutes) than in controls (scintigraphy: 20 +/- 2 minutes; MR imaging: 18 +/- 3) (P < 0.05). CONCLUSIONS: Like liver scintigraphy, functional MR liver imaging using Gd-EOB-DTPA is feasible and can differentiate normal controls from models of biliary and hepatocyte disease.

Animals↗

Differentiation of spontaneous canine breast tumors using dynamic magnetic resonance imaging with 24-Gadolinium-DTPA-cascade-polymer, a new blood-pool agent. Preliminary experience.

RATIONALE AND OBJECTIVES: The author assess the enhancement characteristics over time of spontaneous breast tumors in dogs comparing gadopentetate dimeglumine with a new blood-pool agent (24-gadolinium [Gd]-DTPA-cascade polymer). METHODS: Eighteen dogs with spontaneous breast tumors (5 carcinomas, 4 adenomas, and 9 benign mixed-tissue tumors) underwent dynamic magnetic resonance imaging after intravenous injection of gadopentetate dimeglumine and the blood-pool agent. Signal intensity time curves were followed up to 30 minutes after injection of both agents in the same animal. A nonlinear fitting routine enabled calculation of the delivery and clearance half lives of the contrast agent kinetics in each tumor. RESULTS: For gadopentetate dimeglumine, a fast signal increase was found immediately after intravenous injection, with a subsequent signal decay in all tumors. No difference was observed between the enhancement kinetics of different tumor types after gadopentetate dimeglumine application. Similar kinetics were found in benign lesions after injection of the blood-pool agent. However, in carcinomas the blood-pool agent displayed a slower delivery, delayed peak enhancement, and slower tumor tissue clearance or even a signal plateau of more than 30 minutes. CONCLUSIONS: Dynamic magnetic resonance imaging of breast neoplasms using a blood-pool agent may help to better differentiate between benign and malignant lesions because it demonstrates the enlarged interstitial space and increased capillary permeability in carcinomas.

Adenoma↗

Contrast-enhanced MR imaging assessment of tumor capillary permeability: effect of irradiation on delivery of chemotherapy.

PURPOSE: To assess the effect of x rays on tumor capillary permeability with macromolecular contrast medium (MMCM)-enhanced magnetic resonance (MR) imaging. MATERIALS AND METHODS: One of paired R3230 mammary adenocarcinomas implanted in the flanks of 48 Fischer rats was treated with a single 5- or 15-Gy dose of x rays. After 1 or 3 days, MR imaging in 30 rats was performed unenhanced and enhanced with albumin-(gadolinium diethylenetriaminepentaacetic acid)30 (0.02 mmol gadolinium per kilogram body weight). Signal intensity enhancement was analyzed to estimate fractional blood volume and permeability-surface area product (PS). In 18 irradiated rats, 2.5 mg/kg cisplatin was injected intravenously, and fractional tumor platinum concentrations were measured spectrometrically. RESULTS: MR imaging showed highest capillary permeability 1 day after 15 Gy (PS 110% above control [P<.001]); PS was elevated 57% 1 day after 5 Gy and 63% 3 days after 15 Gy (P<.05). The largest mean tumor platinum fraction occurred 1 day after 15 Gy: 48% versus 20% (control)(P<.05). CONCLUSION: Transient irradiation-induced increase in tumor capillary permeability to cisplatin can be quantified with MMCM-enhanced MR imaging.

Albumins↗

Quantification of liver blood volume: comparison of ultra short TI inversion recovery echo planar imaging (ULSTIR-EPI), with dynamic 3D-gradient recalled echo imaging.

An ultra-short TI inversion recovery echo-planar imaging (ULSTIR-EPI) sequence was designed to reduce the influence of water exchange on fractional tissue blood volume (BV) estimation by measurement of T1-changes induced by a gadolinium-based macromolecular contrast medium (MMCM). Fractional liver BV in rats, estimated by ULSTIR-EPI was compared for accuracy to a fast T1-weighted three-dimensional gradient-echo (3D-SPGR, 3D-spoiled gradient recalled acquisition in a steady state) sequence using an in vitro inductively coupled plasma atomic emission spectroscopy (ICP-AES) assay for BV as a standard. Liver images for fractional BV estimation were acquired in eight rats using both ULSTIR-EPI and 3D-SPGR before and after (within 3 to 12 min) intravenous bolus administration of albumin-Gd-DTPA30 (0.05 mmol Gd/kg). Whereas both MR techniques may be useful for fractional tissue BV estimation, ULSTIR-EPI offers certain advantages including greater accuracy, direct T1 maps, and minimization of transendothelial proton exchange effects. 3D-SPGR imaging offers better spatial resolution, current availability on standard clinical MR systems, and acceptable accuracy.

Albumins↗

Assessment of myocardial perfusion using contrast-enhanced MR imaging: current status and future developments.

Excellent inherent tissue contrast is one of the great promises of clinical magnetic resonance (MR) imaging, but functional information is relatively limited. However, MR imaging complemented by the administration of contrast agents can provide such functional assessment. The perfusion status of the myocardium is one of the most important functional information in cardiovascular imaging. Because the clinical acceptance of a contrast agent is measured by its ability to improve patient outcome and to guide therapy, it is unlikely that detection of myocardial infarction, the final stage of ischemic heart disease, should be the target for contrast media development. It would obviously be better if occult regional myocardial perfusion deficits could be reliably detected. The current article was prepared to help the clinical radiologist to keep pace with new strategies for myocardial enhancement and their potential clinical applicability for detection of early perfusion deficits. Several techniques for noninvasive measurement of myocardial perfusion are currently evolving which have the potential to be introduced into routine MR imaging. Most investigators favor a first-pass analysis of the contrast agent bolus through the myocardium using ultrafast sequences. However, such a technique may require clinical introduction of a blood pool agent. There are good reasons to favor T1-weighted sequences over susceptibility imaging in such first-pass studies. In the future, assessment of myocardial perfusion status using contrast-enhanced MR imaging may be done producing perfusion maps with high spatial resolution (e.g., 256 x 128), with sequences available on most scanners without special hardware requirements (e.g., IR-Turboflash, keyhole imaging), and requiring only a short period of time for examination (approximately 3 min).

Animals↗

Angiographic properties of Gd-DTPA-24-cascade-polymer--a new macromolecular MR contrast agent.

PURPOSE: A new macromolecular MR contrast agent, Gd-DTPA-24-cascade-polymer, was assessed for MR angiography of peritumoral vessels in rats. MATERIAL AND METHODS: High resolution 3D-SPGR (TR/TE 100/5ms, alpha = 90 degrees) angiograms were acquired in 10 Fischer rats bearing subcutaneous R3230 mammary adenocarcinomas. MRI was performed before, immediately and 40 min after administration of Gd-DTPA (0.1 mmol Gd/kg), and after either Gd-DTPA-cascade-polymer or albumin-(Gd-DTPA)30 (each 0.05 mmol Gd/kg). A semi-quantitative analysis of small peritumoral vessels and tumor rim enhancement was performed on maximum intensity projection (MIP) angiograms using a 4-point scoring system. A quantitative analysis compared vascular signal-to-background-(S/B), signal-to-noise-, and contrast-to-noise-ratio. RESULTS: Gd-DTPA produced a transient and low-scoring vessel definition (0.2 +/- 0.1), but strong rim enhancement (score 1.7 +/- 0.1). The cascade polymer resulted in better but submaximal vessel delineation (score 1.6 +/- 0.3, S/B 5.0 +/- 0.2) and strong rim enhancement (score 1.8 +/- 0.1). Albumin-(Gd-DTPA)30 produced the best and most time-persistent angiograms (score 2.6 +/- 0.2, S/B 7.4 +/- 0.2), but minimal rim enhancement (score 0.3 +/- 0.2). CONCLUSIONS: The Gd-DTPA-24-cascade-polymer demonstrated the useful combination of strong tumor rim enhancement and detailed angiographic definition of peritumoral vessels. These are advantages associated with extracellular and blood pool contrast media, respectively.

Adenocarcinoma↗

Biodistribution and excretion of 153Gd-labeled gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid following repeated intravenous administration to rats.

RATIONALE AND OBJECTIVES: We investigated the distribution of radioactivity in tissues and organs and its disappearance following repeated intravenous (i.v.) administration of 153Gd-labeled gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) to rats. METHODS: A high total dose of 250 mumol/kg of 153Gd-labeled Gd-EOB-DTPA (a daily injection of 50 mumol/kg is equivalent to 92.5 kBq per animal on 5 consecutive days) was given to conscious rats by fast i.v. injection via a tail vein. The organ distribution and the body elimination into urine and feces were investigated at time points 3, 7, 14, and 21 days following the last injection; five animals were used at each time point. All samples were measured by gamma counting of 153Gd over a 10-min period. RESULTS: The radioactivity quickly disappeared from the body, mostly through feces. In the liver, no radioactivity could be detected at 3 days postinjection. At 21 days postinjection, only 0.002% of the gadolinium injected was detected, the vast majority (approximately 95%) of which was found in the kidneys. CONCLUSION: After repeated i.v. administration of a total dose of 250 mumol/kg of 153Gd-labeled Gd-EOB-DTPA, the elimination from the body was found to be 99.998% complete. Only negligible long-term retention of radioactive gadolinium was observed despite the relatively high dose injected. No perceptible evidence for decomplexation of Gd-EOB-DTPA could be found.

Animals↗

Investigation of mechanisms influencing the accumulation of ultrasmall superparamagnetic iron oxide particles in lymph nodes.

RATIONALE AND OBJECTIVES: The current study was designed to investigate the lymph node accumulation mechanisms of dextran-coated ultrasmall superparamagnetic iron oxide particles (USPIO) in rats. METHODS: The iron deposition in the lymph nodes after intravenous administration of USPIO at a dose of 200 mumol Fe/kg was measured in vitro by inductively coupled plasma atomic emission spectrometer in control rats, in rats after depletion of complement C3, after induction of antidextran antibodies, and with prior ligation of afferent lymphatic vessels. The results were correlated with baseline iron concentration and histology. RESULTS: A significant increase in iron concentration but unequal distribution between central and peripheral nodes occurred after administration of USPIO in rats. Much less accumulation was observed in guinea pigs. In rats, the nodal uptake of USPIO was not impaired by depletion of complement C3 using cobra venom factor. The central lymph nodes (mesenteric nodes) showed significantly more accumulation of iron particles in the presence of antidextran antibodies induced by dextran preimmunization. Afferent lymphatic vessel ligation did not effect iron particle accumulation. CONCLUSIONS: Accumulation of USPIO in lymph nodes is largely species-dependent but is independent of afferent lymphatic flow and of C3 complement opsonization in plasma. However, regional distribution of particles can be influenced by preimmunization using dextran.

Animals↗

A toxicologic risk for using manganese complexes? A literature survey of existing data through several medical specialties.

This article summarizes data from the literature about biologic functions, toxicity, and biokinetics of manganese to help the reader assess the importance of complex stability of manganese-based contrast agents. Free manganese may present a greater risk than free gadolinium, especially because it has a physiologic role and can therefore trigger multiple functions. Of particular interest are the deleterious effects of manganese on the central nervous system (it can cross the intact blood-brain barrier) and on developing life (it penetrates the placental barrier as well and is teratogenic). After intravenous contrast injection, normal (enteral) regulation mechanisms for manganese homeostasis are bypassed, and there is a danger of individual overdosing. Excess manganese, for example in patients with chronic liver disease or with chronic parenteral nutrition, has already been detected by magnetic resonance imaging in the basal ganglia and was found to coincide with neurologic symptoms. Decomplexation with release of free manganese substantially prolongs the elimination of the metal because manganese can be excreted only slowly via the biliary system. This may be of particular importance in patients with impaired hepatic function. Although minimal amounts of free manganese ions are not considered harmful to the human body, significant decomplexation of manganese complexes will require careful analysis of the diagnostic benefit versus the potential risk posed by the free metal ions.

Basal Ganglia↗

Phase I clinical evaluation of Gd-EOB-DTPA as a hepatobiliary MR contrast agent: safety, pharmacokinetics, and MR imaging.

PURPOSE: To determine the safety, pharmacokinetics, and magnetic resonance (MR) imaging results of gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) as a contrast agent for use in hepatobiliary MR imaging. MATERIALS AND METHODS: Gd-EOB-DTPA was tested at doses of 10, 25, 50, and 100 mumol per kilogram of body weight. Results of laboratory tests, clinical measurements, and pharmacokinetic data were obtained in 44 healthy volunteers in a double-blind, randomized, placebo-controlled design. MR images were obtained in another 16 healthy volunteers before and up to 6 hours after fast intravenous administration of Gd-EOB-DTPA. RESULTS: Gd-EOB-DTPA was well tolerated, with no important side effects or changes in laboratory parameters. Homogeneous enhancement of liver parenchyma was observed immediately after injection of the contrast agent. Peak liver signal intensity was noted 20 minutes after injection, followed by plateaulike enhancement over about 2 hours. The common bile duct was hyperintense within 10 minutes after injection in all volunteers. CONCLUSION: Gd-EOB-DTPA is safe and efficient for MR imaging of the liver.

Adult↗

Dynamic contrast-enhanced MR imaging of the upper abdomen: enhancement properties of gadobutrol, gadolinium-DTPA-polylysine, and gadolinium-DTPA-cascade-polymer.

The enhancement properties of gadobutrol (40 and 80 mumol/kg body weight, 550 daltons), gadolinium-DTPA-polylysine (20 mumol/kg body weight, 53,000 daltons) and gadolinium-DTPA-cascade-polymer (20 mumol/kg body weight, < 30,000 Daltons) were investigated in abdominal MR imaging using a pig model (n = 24). Signal intensities before and after contrast media application were assessed using a fast single slice FLASH sequence. Measurements were made every 4 s within the first 116 s, every minute between 4 and 10 min and after 15, 20, 30, 40, 50, 60, 90, and 120 min after contrast media injection. Injection of gadobutrol resulted in typical signal intensity curves characterizing it as an extracellular agent similar to gadopentetate dimeglumine. Significant enhancement was found in all tissues except the trunk muscles when the lower dose was administered. Gadolinium-DTPA-polylysine injection resulted also in significant enhancement of the liver, the pancreas, and the renal cortex, but not of the trunk muscle, reflecting its blood pool properties known also from other macromolecular contrast agents. The signal intensity curves obtained after gadolinium-DTPA-cascade-polymer injection were similar to those obtained after polylysine injection, stressing the blood pool character of this new type of blood pool agent.

Abdomen↗

Elimination of gadolinium-ethoxybenzyl-DTPA in a rat model of severely impaired liver and kidney excretory function. An experimental study in rats.

RATIONALE AND OBJECTIVES: The authors investigated whether gadolinium-ethoxybenzyl-DTPA (Gd-EOB-DTPA) can be eliminated in the absence of the two usual excretory pathways (urinary or biliary) and whether a remaining excretory pathway is able to compensate for impaired liver or kidney function. METHODS: The study was performed using two groups of animals: group A animals underwent ligation of the common bile duct, and group B animals underwent ligation of the renal blood vessels. A dose of 0.1 mmol/kg Gd-EOB-DTPA or Gd-DTPA (control) was injected via a tail vein. Bile or urine were collected in fractions of 0 to 1, 1 to 2, 2 to 4, and 4 to 8 hours after administration of either contrast agent. At the end of the experiments, detainment of the contrast agents was determined by measurement of Gd concentrations. RESULTS: Most of the Gd-EOB-DTPA was rapidly cleared from the body: 89.4% +/- 7.5% of the injected dose within 4 hours after bile duct ligation (group A) and 87.0% +/- 6.0% within 1 hour after ligation of renal vessels (group B). Eight hours after injection of Gd-EOB-DTPA, 3.0% +/- 2.4% of the administered dose of this contrast agent was found in the carcasses of group A animals, and 1.3% +/- 0.6% in carcasses of group B animals. By comparison, at 8 hours after injection, 1.9% +/- 3.2% of the injected Gd-DTPA was found in the carcasses of group A animals (no statistical significant difference as compared with Gd-EOB-DTPA), and 96.3% +/- 3.3% in carcasses of group B animals. CONCLUSIONS: In the rat model, the magnetic resonance imaging contrast agent Gd-EOB-DPTA is rapidly and effectively eliminated by virtue of its dual-elimination pathway. The dysfunction of liver or kidney may be fully compensated by the remaining elimination pathway.

Animals↗

MR imaging evaluation of liver enhancement by Gd-EOB-DTPA in selective and total bile duct obstruction in rats: correlation with serologic, microcholangiographic, and histologic findings.

PURPOSE: To investigate the behavior and potential application of the hepatobiliary magnetic resonance (MR) imaging contrast agent gadolinium-ethoxybenzyl (EOB)-diethylene-triamine-pentaacetic acid (DTPA) in cholestasis. MATERIALS AND METHODS: Rat models of selective biliary obstruction (SBO) (n = 20) and total biliary obstruction (TBO) (n = 14) were used. Serial Gd-EOB-DTPA-enhanced MR images were obtained, and the findings were correlated with serologic, microcholangiographic, and histologic findings. RESULTS: In SBO rats, statistically significantly prolonged enhancement of ligated lobes occurred during the acute phase (P < .01) but was absent during the chronic phase owing to bile collateral vessels. In TBO rats, statistically significantly lower liver enhancement (P < .01) was observed as long as the obstruction persisted, until collateral bile ducts developed. CONCLUSION: The distinction between obstructed and unobstructed liver on Gd-EOB-DTPA-enhanced MR images suggests a novel application for visualizing cholestasis.

Animals↗

[Contrast medium enhanced MR angiography].

Magnetic resonance angiography (MRA) protocols are based on standard sequence protocols like time of flight MRA, which evaluates inflowing spins. This technique is limited by a variety of artifacts like the saturation artifact via turbulent blood flow. Contrast media diminish these artifacts like extracellular agents and blood-pool contrast media. The clinical value of the contrast-enhanced MRA for cerebral pathologies is based on the use of the paramagnetic contrast agent Gd-DTPA. For extracerebral diseases this technique is restricted because of the simultaneous visualization of both arterial and venous vascular territories. Occult venous sinus thrombosis or AV malformations are clinical essential indications for the use of C-MRA. Experimental data prove the excellent contrast abilities of blood-pool agents like Gd-DTPA-polylysin or Gd-DTPA-albumin, which demonstrate long intravascular persistence and retarded excretion.

Algorithms↗

[Progress in magnetic resonance tomography of the liver: value of ultra-rapid imaging and liver-specific contrast media].

Ongoing technical improvements in magnetic resonance imaging (MRI) and the development of liver-specific contrast agents are likely to have an impact on the clinical assessment of liver disease. Technical progress towards methods of motion-free MRI and concepts of liver-specific contrast agents are presented. The potential impact of these developments on clinical medicine is discussed.

Animals↗