Biomedical subjects

A Mühler

Publications and source records attributed to A Mühler.

At least 55 records · Page 3Linked to original sources

PubMed1993

Measurement of capillary permeability to macromolecules by dynamic magnetic resonance imaging: a quantitative noninvasive technique.

A simple, linear kinetic model has been developed for the noninvasive assessment of capillary permeability to macromolecules in the rat by dynamic magnetic resonance imaging using albumin-Gd-DTPA. Data required by the model are signal intensity responses from a target tissue and a venous structure such as inferior vena cava before and after bolus intravenous injection of albumin-Gd-DTPA. Additional requirements include an early temporal resolution of approximately one image/min and a blood sample for hematocrit. The model does not require measurement of albumin-Gd-DTPA concentration in either arterial or venous blood. Pilot experiments suggest that this technique is adequate for estimation of the fractional leak rate of macromolecules from plasma to interstitial water as well as tissue plasma volume, the product of which yields a measure of the permeability surface area product of the tissue if the extraction fraction is modest (< 0.2). The technique may be generally applicable to the study of abnormal capillary permeability in humans as well as animals.

Algorithms↗

PubMed1993

Quantification of tissue plasma volume in the rat by contrast-enhanced magnetic resonance imaging.

Magnetic resonance imaging enhanced with a macromolecular contrast medium (MMCM), albumin-Gd-DTPA, was used to estimate the plasma volume in vivo in the myocardium, lung, liver, and skeletal muscle of 10 normal rats. The plasma volumes of the same tissues in a parallel group of six rats were estimated in vitro by a conventional radioisotopic technique (111In-transferrin). Plasma volumes of myocardium, lung, liver, and skeletal muscle estimated by the MR technique (microliter plasma cc-1 of tissue) were 101, 109, 163, and 11.0, respectively, while plasma volumes measured by the 111In-transferrin radioisotope technique (mg plasma g-1 of tissue) were 78.6, 215, 143, and 11.2, respectively. Assuming a ratio of densities of aerated lung to blood of 0.45 and of other tissues to blood of 1.0, correlation between the methods was excellent (R2 = 0.99) indicating that MR imaging enhanced with MMCM permits reliable in vivo estimation of tissue plasma volume in the rat.

Albumins↗

PubMed1993

Pulmonary oxygen toxicity: demonstration of abnormal capillary permeability using contrast-enhanced MRI.

An animal model of oxygen-induced pulmonary injury was used to assess the potential of contrast-enhanced MRI to identify and quantify abnormal capillary permeability. Sprague-Dawley rats were exposed to 100% oxygen for 48 h (n = 5) or 60 h (n = 9). Axial spin-echo MR images were acquired in intubated, anesthetized rats with ECG-gating (TR 400; TE 6) immediately or 7 days after the cessation of oxygen exposure. Polylysine-Gd-DTPA, a macromolecular paramagnetic blood-pool marker, was then given intravenously and the lungs were serially imaged for 42 to 47 min to monitor changes in signal intensity. Pulmonary enhancement was stable in rats exposed to 48 h of oxygen, and in rats exposed to 60 h of oxygen and given 7 days to recover. However, animals exposed to 100% oxygen for 60 h without a period of recovery showed a progressive increase in lung signal intensity for 15 min after polylysine-Gd-DTPA. Pleural effusions also showed progressively increasing signal, reflecting a capillary endothelial leak. A two compartment model describing the kinetics of polylysine-Gd-DTPA in the plasma and interstitial water of the lung was consistent with the dynamic MRI data and allowed estimation of the fractional leak rate (0.235 min-1) of the contrast agent from plasma to interstitial water. Given the assumption of our kinetic model, MRI following intravenous administration of polylysine-Gd-DTPA can be used to quantitate changes in capillary integrity induced by hyperoxia, including acute capillary leakiness and return to normal endothelial integrity with recovery from hyperoxic injury.

Animals↗

PubMed1993

Gadolinium-ethoxybenzyl-DTPA, a new liver-directed magnetic resonance contrast agent. Absence of acute hepatotoxic, cardiovascular, or immunogenic effects.

RATIONALE AND OBJECTIVES: Gadolinium-ethoxybenzyl-DTPA (Gd-EOB-DTPA) is a recently introduced experimental magnetic resonance (MR) contrast agent for hepatic imaging. Although liver enhancement has been investigated in a number of animal models, tolerance evaluations of Gd-EOB-DTPA injection have been limited. METHODS: The authors investigated acute hepatotoxicity in an isolated perfused rat liver model, cardiovascular effects in the anesthetized rat, and potential immunogenicity of Gd-EOB-DTPA using detection of specific antibodies. RESULTS: Using perfused rat liver model, no significant deviation could be observed for functional parameters, liver enzymes, or potassium release, comparing Gd-EOB-DTPA to a control, but there was a significant choleresis (+250% bile flow). Hemodynamic effects of Gd-EOB-DTPA were observed after femoral bolus injection, but only with relatively high dosages (0.3-0.5 mmol/kg, 10-fold the likely clinical dose in humans). Experimental conditions, idealized for antibody induction, failed to cause an IgG immune response to Gd-EOB-DTPA in the intact rat. CONCLUSIONS: The results further support preliminary conclusions that Gd-EOB-DTPA is a well-tolerated MR contrast agent.

Animals↗

PubMed1993

Acute liver rejection: evaluation with cell-directed MR contrast agents in a rat transplantation model.

Enhancement patterns with gadolinium (4s)-4-(4-ethoxybenzyl)-3,6,9-tris (carboxylatomethyl)-3,6,9-triazaundecandioic acid (EOB) diethylenetriaminepentaacetic acid (DTPA), a hepatocyte-directed magnetic resonance (MR) contrast agent, and superparamagnetic iron oxide particles (SPIO), a Kupffer cell-directed contrast agent, were compared at MR imaging in rat models of allogeneic and syngeneic liver transplantation. Light and electron microscopy were performed to monitor the morphologic changes in these livers and revealed typical findings in acute rejecting liver (allogeneic transplants) and normal architecture in syngeneic transplants. Liver enhancement with Gd-EOB-DTPA at MR imaging was delayed and prolonged with transplantation, and even more with rejection, but the level of enhancement when compared with that of control rats remained unaffected. Uptake of SPIO was decreased in the acutely rejecting livers but was normal in the syngeneic transplantation model. Enhanced MR imaging with cell-directed contrast agents depicted decreased phagocytotic activity in acute transplant rejection and enabled the excretory function of hepatocytes to be monitored. Additionally, Gd-EOB-DTPA may be applied advantageously for detection of focal lesions in transplanted livers.

Acute Disease↗

PubMed1993

Acute fracture of the femoral neck: assessment of femoral head perfusion with gadopentetate dimeglumine-enhanced MR imaging.

OBJECTIVE: Evaluation of the perfusion and viability of the femoral head after fracture of the femoral neck is important because the outcome of conservative treatment or joint-preserving surgery is adversely affected by the development of capital osteonecrosis. We evaluated the use of MR imaging, before and after IV administration of gadopentetate dimeglumine, for assessing perfusion of the femoral head in 13 patients with acute fracture of the femoral neck. SUBJECTS AND METHODS: Multiecho (1600/30-240 [TR/TE]) MR images were obtained before contrast administration and gradient-echo (315/14, 90 degrees flip angle) MR images were obtained both before and after contrast administration. MR findings were correlated with findings on superselective digital subtraction angiograms of the vessels supplying the femoral head and with clinical-radiographic follow-up for at least 12 months. RESULTS: Digital subtraction angiography showed impaired blood supply to the femoral head in five patients. On contrast-enhanced MR images of these patients, the femoral head did not enhance and was lower in signal intensity than were the enhancing femoral shaft and neck distal to the fracture and the enhancing femoral head on the unaffected side. In the patients with persistent perfusion, contrast-enhanced MR images showed a uniform increase in signal intensity in the femoral shaft and neck as well as the femoral head; the femoral head on the fractured side showed contrast enhancement similar to that on the healthy side. CONCLUSION: These preliminary results indicate that contrast-enhanced MR imaging may be useful for noninvasive evaluation of femoral head perfusion after fracture of the femoral neck. MR findings also may aid the clinician in deciding between joint-preserving therapy and hip arthroplasty.

Acute Disease↗

PubMed1992

Hemodynamic effects of bolus injection of gadodiamide injection and gadopentetate dimeglumine as contrast media at MR imaging in rats.

The trend to administer contrast agents for magnetic resonance (MR) imaging by rapid injection and to use higher doses necessitates additional safety assessments with regard to potential hemodynamic effects. The current study was designed to evaluate the hemodynamic effects or rapid injection of increasing doses of gadodiamide injection (gadolinium diethylenetriaminepentaacetic acid bismethylamide) and gadopentetate dimeglumine. Each animal received incremental doses (0.1, 0.3, and 0.5 mmol/kg) of either contrast agent via the left jugular vein as a rapid bolus (1-2 seconds). Gadodiamide injection caused no hemodynamic alterations; however, gadopentetate dimeglumine caused dose-dependent cardiodepressive effects. At a dose of 0.5 mmol/kg, gadopentetate dimeglumine transiently decreased left ventricular end-systolic pressure by 25%, systolic arterial pressure by 34%, and positive peak differential quotient of pressure change against time by 43% of preinjection values. All hemodynamic parameters returned to baseline in the first 3-5 minutes.

Animals↗

PubMed1992

Contrast-enhanced MR imaging of the lung: assessments of ventilation and perfusion.

The use of aerosolized gadopentetate dimeglumine to define regional lung ventilation and of intravenously administered polylysine-(gadopentetate dimeglumine)40 to assess regional lung perfusion was investigated. In 10 healthy rats who breathed aerosolized gadopentetate dimeglumine (0.25 mol/L) for 5 minutes, pulmonary signal intensity increased diffusely in both lungs by more than 70%. When the same animals received intravenously administered polylysine-(gadopentetate dimeglumine)40 (0.1 mmol of gadolinium per kilogram), there was an additional 300% enhancement of the pulmonary parenchyma. In a rat model of acute unilateral pulmonary embolism (n = 5), perfusion defects were identified after administration of polylysine-(gadopentetate dimeglumine)40, but no ventilation abnormality was seen after inhalation of gadopentetate dimeglumine. In a rat model of acute unilateral airway obstruction (n = 5), only the ventilated right lung enhanced after inhalation of gadopentetate dimeglumine. In four of these animals, the focal ventilation defect was accompanied by a matched decrease in perfusion, seen after enhancement of the blood pool with polylysine-(gadopentetate dimeglumine)40.

Aerosols↗

PubMed1992

Amelioration of cardiodepressive effects of gadopentetate dimeglumine with addition of ionic calcium.

Doses of gadopentetate dimeglumine of 0.1-0.5 mmol/kg cause cardiodepressive effects when injected as a rapid central bolus into the left jugular vein. This study evaluated the hemodynamic effects of this magnetic resonance imaging contrast medium with and without calcium supplementation in a rat model. Also, the potential of gadopentetate dimeglumine to bind ionized serum calcium was investigated in vitro. Addition of calcium ions resulted in dose-dependent attenuation of the hemodynamic depression induced by gadopentetate dimeglumine alone. The cardiodepressive response was negated for a 0.1-mmol/kg dose of the contrast agent by addition of 6 mumol/kg of calcium, for a 0.3-mmol/kg dose by addition of 12 mumol/kg of calcium, and for a 0.5-mmol/kg dose by addition of 18 mumol/kg of calcium. Concentrations of 2 and 4 mmol/L of gadopentetate dimeglumine were found to bind 5.1% and 10.1% of the ionized calcium in rat serum under in vitro conditions, respectively.

Animals↗

PubMed1992

Hepatobiliary enhancement with Gd-EOB-DTPA: comparison of spin-echo and STIR imaging for detection of experimental liver metastases.

Gadolinium (4S)-4-(4-ethoxybenzyl)-3,6,9-tris(carboxylatomethyl)-3,6,9- triazaundecandioic acid-disodium salt (EOB-DTPA) ethoxybenzyl is a new hepatobiliary magnetic resonance (MR) contrast agent with dual elimination: 75% through the liver and bile and 25% through the kidneys in normal rats. In this study, Gd-EOB-DTPA was evaluated in a rodent model of metastatic liver disease to measure both relative enhancement and lesion-to-liver contrast. A secondary goal was to compare the relative performance of spin-echo (SE) and short inversion time inversion-recovery (STIR) imaging to demonstrate enhancement with Gd-EOB-DTPA. After administration of 0.1 mmol of Gd-EOB-DTPA per kilogram, liver signal increased (positive enhancement) more than 200% with the use of the SE technique and declined (negative enhancement) by more than 80% with use of the STIR technique. Only minimal enhancement of implanted liver tumor was observed. Unlike the tumor, the gall-bladder and lumen of the duodenum were progressively enhanced over time. The lesion-to-liver contrast increased by approximately 500% with both the SE and STIR techniques after administration of Gd-EOB-DTPA.

Acetates↗

PubMed1992

Evaluation of radiation-induced liver injury with MR imaging: comparison of hepatocellular and reticuloendothelial contrast agents.

Gadolinium (4s)-4-(4-ethoxybenzyl-3,6,9-tris(carboxylato-methyl)-3,6,9- triazaudecandioic acid (EOB) diethylenetriaminepentaacetic acid (DTPA), a hepatocellular-directed magnetic resonance (MR) contrast agent, and coated superparamagnetic iron oxide particles (SPIO), a Kupffer cell-directed contrast agent, were compared for uptake and enhancement in a rodent model of radiation-induced liver injury. A single x-irradiation exposure (50-70 Gy) was delivered to one side of the liver in 18 rats. MR imaging was performed 3 days after x irradiation with sequential injections of the two contrast agents in the same rats. Additionally, biliary excretion of Gd-EOB-DTPA was quantified after whole-liver irradiation in five rats. Electron microscopy of the irradiated liver demonstrated mitochondrial injury in both hepatocyte and Kupffer cell populations. With Gd-EOB-DTPA, however, liver enhancement and biliary excretion were not affected by irradiation. Uptake of SPIO was decreased in the irradiated portion of the liver, with a precise demarcation between irradiated and nonirradiated zones at MR imaging.

Animals↗

PubMed1992

Differentiation of alveolitis and pulmonary fibrosis with a macromolecular MR imaging contrast agent.

The ability of macromolecular contrast agent (polylysine-[gadopentetate dimeglumine]) to allow differentiation of pulmonary fibrosis and alveolitis at magnetic resonance imaging was investigated. Lung damage was induced by means of left bronchial instillation of 200 micrograms of cadmium chloride. Rats were imaged 3 hours (early alveolitic stage, n = 5), 24 hours (late alveolitic stage, n = 5), and 8 days (fibrotic stage, n = 5) later. Rats imaged 3 hours after cadmium chloride instillation demonstrated a gradually increasing contrast enhancement over 45 minutes (from 314% +/- 110 to 476% +/- 69 over baseline [P less than .01]), indicating a leak of paramagnetic macromolecules from the intravascular into the extravascular spaces. Conversely, lung enhancement remained virtually constant after injection of contrast material in contralateral control lungs and in damaged lungs imaged 24 hours and 8 days after cadmium chloride instillation. Furthermore, the enhancement in the fibrotic lung was lower (170% +/- 50) than that in the alveolitic and control lungs (320% +/- 65 and 298% +/- 61, respectively), indicating a decrease in plasma volume in the fibrotic lung. A macromolecular contrast agent can facilitate the differentiation between the exudative and fibrotic phases of interstitial lung disease.

Animals↗

PubMed1992

Gadolinium-ethoxybenzyl-DTPA, a new liver-specific magnetic resonance contrast agent. Kinetic and enhancement patterns in normal and cholestatic rats.

OBJECTIVES: Gadolinium-ethoxybenzyl-DTPA (Gd-EOB-DTPA) is a new hepatobiliary magnetic resonance imaging (MRI) contrast agent with a dual elimination: 70% via the liver and bile and 30% via the kidney in normal rats. The abdominal enhancement patterns of this new compound and the uptake mechanism by the liver were studied in rats using tissue relaxometry and MRI. METHODS: Twelve normal rats, 33 rats treated with agents designed to inhibit biliary excretion of the agent, and 6 rats with surgically ligated common bile ducts received Gd-EOB-DTPA intravenously. Distribution and excretion were measured by MR relaxometry. MR signal intensity was measured over time for liver, kidney, and bowel. RESULTS: In normal animals, 0.1 mmol/kg Gd-EOB-DTPA induced a significantly greater (200%) and more prolonged liver signal enhancement (100% at 30 minutes) than Gd-DTPA at the same dose. Either hyperbilirubinemia, induced by common bile duct ligation, or bromosulfophtalein (BSP) infusion inhibited liver uptake of Gd-EOB-DTPA, resulting in a preferential elimination via the kidney. Taurocholate (TC), an inhibitor of the bile acid transporter, was unable to block the liver uptake of Gd-EOB-DTPA. Blood half-lives of Gd-EOB-DTPA in rats were 2.4 minutes for the first component and 8.2 minutes for the second. CONCLUSIONS: Data indicate that transport of Gd-EOB-DTPA through the liver into bile is driven by the organic anion transporter. The relation between enhancement of liver and kidney may be diagnostically useful to indirectly evaluate liver excretory function. Yet, persistent enhancement of liver, even in the presence of severe hyperbilirubinemia, should be sufficient to identify focal mass lesions.

Animals↗

PubMed1991

[The accuracy of the imaging procedures (sonography, MRT, CT, angio-CT,nuclear medicine) in characterizing liver tumors].

In a prospective study, an attempt was made to determine the specificity of various imaging methods for defining tumours of the liver rather than their ability to demonstrate them. It was based on 130 patients with histologically confirmed lesions (33 haemangiomas, 17 FNH, 4 hepatocellular adenomas, 28 HCC, 36 adenocarcinoma metastases). The methods were MRT (130 cases), sonography (119), CT (122), dynamic arterial angio-CT (15), 99TC-EHIDA or blood pool scintigraphy (4 FNH, haemangiomas, HCC, 44 cases). MRT showed somewhat better results (accuracy 80%) than CT (73%) and angio-CT (73%) in demonstrating the type of lesion. The results of scintigraphy (53%) and sonography (69%) were rather worse. The range of accuracy for MRT, CT and sonography varied from 94% (haemangiomas with MRT) to 47% (FNH with sonography).

Biopsy↗

PubMed1990

[A frequency analysis and evaluation of the criteria for dynamic CT and a test of the CT diagnosis of space-occupying lesions of the liver].

In a retrospective study the findings of dynamic CT investigations in 185 patients with histologically confirmed hepatic masses were analysed and related to 47 criteria which have been described in the literature. The criteria with the highest value for making a specific diagnosis have been defined for seven different lesions (abscess, adenoma, FNH, haemangioma, adenocarcinoma metastases, metastases from other tumours, HCC). We found agreement with the literature in the following: the target phenomenon for abscesses, central scarring for FNH, spreading enhancement for haemangiomas and irregularity of the liver contour in the absence of subcapsular tumours for HCC. By combining a number of criteria it was possible to suggest the type of lesion retrospectively. The predictive value was found to range from 73% to 100%, a definite diagnosis was possible in only 64%.

Diagnosis, Differential↗

PubMed1990

[Differential diagnosis by MRT of cavernous hemangiomas and malignant tumors of the liver--advantages of the multi-echo technic].

With a retrospective analysis of images from 39 patients with histologically proven liver tumours we tried to determine the best MRT-parameter for detection of cavernous hemangioma (n = 19) and its differentiation from malignoma (metastases n = 17, HCC n = 5). The best differentiation was achieved with the contrast-to-noise ratio between lesion and liver in multi-echo-images with TR/TE = 2,000/210 ms and a definite limit with an accuracy of 84% for hemangioma and 91% for malignoma. The respective intensity ratios (lesion/liver) were 95% and 77%. T2-relation times and the T1- and T2-ratios were also calculated. In contrary to the literature we think that these parameters are not sufficiently discriminating.

Adult↗

PubMed1989

[An intra- and interobserver study of the accuracy of dynamic CT of hepatic space-occupying lesions].

An intra- and interobserver study with 10 physicians was undertaken in order to determine the accuracy of differentiation regarding the type and benign/malignant of hepatic space-occupying processes. By "conditioning" of the observers a significant reduction of doubtful cases with a slight increase in diagnostic accuracy (10% in differentiating of benign/malignant and 5% of the type) relative to our first study was achieved. Marked increases were found for 3 little experienced observers. By informing the observers on the diagnostic criteria for hepatocellular carcinoma the percentage of correct decisions was significantly increased.

Humans↗

PubMed1988

CT diagnosis of pedunculated liver tumours.

Liver tumours with extrahepatic location are uncommon. They show specific CT criteria with respect to blood supply. Various CT criteria have been analysed in 10 tumours, including three hepatocellular adenomas, two focal nodular hyperplasias, four cavernous haemangiomas and one hepatocellular carcinoma. Correct diagnosis was obtained only in haemangiomas with their characteristic hyperdense blood pools, and in one hepatocellular carcinoma. CT criteria of the ten pedunculated tumours are discussed, to with the aim of adding to our knowledge of the diagnostic relevance of CT.

Adenoma↗