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R C Brasch

Publications and source records attributed to R C Brasch.

At least 19 recordsLinked to original sources
PubMed1992

Hypercarbia-induced changes in cerebral blood volume in the cat: a 1H MRI and intravascular contrast agent study.

Cerebral blood volume changes with arterial carbon dioxide were monitored by proton T1-weighted MR images following administration of the intravascular contrast agent Gd-DTPA labeled with human serum albumin. Without MR contrast, no significant image intensity changes were observed with PaCO2. Following contrast, regional brain image intensities increased significantly over control (0% inspired CO2) in cortical gray, white, and basal ganglia regions with increasing PaCO2 and returned to control intensities upon return to 0% inspired CO2. Imaging of through-plane and in-plane phantoms was performed to assess flow effects. Signal losses of 2 and 6% (relative to no flow) were observed for bulk velocities of 5 mm/s at TE values of 15 ms. An intravascular contrast agent may be useful for MRI monitoring of local cerebral blood volume changes during cerebral perturbations.

Adipose Tissue↗
PubMed1992

Magnetic resonance imaging detection of an experimental pulmonary perfusion deficit using a macromolecular contrast agent. Polylysine-gadolinium-DTPA40.

RATIONALE AND OBJECTIVES: This study was designed to evaluate the potential of a blood-pool magnetic resonance (MR) contrast agent, polylysine-gadolinium-DTPA40 (polylysine-Gd-DTPA40) for detecting pulmonary perfusion defects. MATERIALS AND METHODS: Pulmonary emboli were induced in 10 rats by venous injection of 0.2 mL of air. Axial spin-echo images were acquired (TR = 800 mseconds; TE = 6 mseconds) before and after air injection and serially after the administration of polylysine-Gd-DTPA40. The embolism model was confirmed by scintigraphy using 99mTc-macroaggregated albumin. RESULTS: Signal intensity differences between normal and embolized lungs before and after the air injection were less than 25%. After polylysine-Gd-DTPA40 administration, signal intensity of the perfused lung increased more than 200%, whereas the embolized lung increased by only 25%. Signal intensities of the perfused lung remained stable for 1 hour, whereas signal intensities of the embolized lung gradually increased for 20 minutes as the air embolus dissolved. CONCLUSION: Magnetic resonance imaging (MRI) enhanced with a macromolecular blood-pool contrast agent can be used to detect acute pulmonary embolism in a confirmed animal model.

Animals↗
PubMed1992

Magnetic resonance imaging demonstration of pharmacologic-induced myocardial vasodilatation using a macromolecular gadolinium contrast agent.

RATIONALE AND OBJECTIVES: Adenosine is a potent vasodilator used clinically in nuclear scintigraphy to assess coronary artery reserves. The potential to identify this vasodilating effect of adenosine using magnetic resonance imaging (MRI), which is superior in spatial resolution to nuclear scintigraphy, combined with a blood-pool MRI contrast agent, was investigated in normal rats. METHODS: Groups of Sprague-Dawley rats received successive infusions of either adenosine (3 mg/kg/minute; n = 7) or dipyridamole (negative control; up to 1.0 mg/kg/minute; n = 9), both before and after contrast enhancement, with a macromolecular blood-pool MRI contrast agent, albumin-gadolinium-DTPA35 (Gd-DTPA35) (4.0 mumol Gd per kilogram). Electrocardiographically (ECG) gated MRIs (2.0 Tesla), acquired serially before and after contrast enhancement, and with and without either adenosine or dipyridamole infusions, to monitor potential pharmacologic responses. RESULTS: During repeated infusions of adenosine, the postcontrast myocardial enhancement, reflecting blood volume, increased significantly (P < .05), up to 150%, compared with pre-adenosine enhancement. Infusions of dipyridamole, pharmacologically inactive in rats, produced no change in myocardial enhancement. CONCLUSIONS: The increased myocardial signal intensity observed during adenosine infusions after enhancement of the blood pool can be attributed to increased blood volume accompanying coronary vasodilatation. The method, which does not require a continuous infusion of contrast agent, has potential for the clinical evaluations of coronary artery reserves.

Adenosine↗
PubMed1992

Comparison of vascular opacification after bolus injection of iodixanol-320 iohexol-350.

RATIONALE AND OBJECTIVES: The vascular opacification characteristics of a new nonionic, dimeric contrast agent, iodixanol, have been compared with a nonionic, monomeric agent, iohexol, using ultrafast computed tomography (UFCT). METHODS: In 10 experiments with mongrel dogs, the contrast agents were alternately injected into the animal's left atrium, and UFCT images were obtained at four cross-sectional levels through the carotid arteries. Time-density curves were then obtained for each carotid artery and each agent. The peak height and area under the curves were compared for each agent. RESULTS: Iohexol provided significantly (P < or = .05) greater opacification, determined by paired Student's t tests. CONCLUSION: This result was predicted from the greater iodine concentration of iohexol (350 mg/mL) compared with iodixanol (320 mg/mL); the difference was greater than expected based on iodine content alone.

Animals↗
PubMed1992

New directions in the development of MR imaging contrast media.

Ongoing developments in contrast media for magnetic resonance (MR) imaging should lead to an improvement in sensitivity for the detection of disease, better definition of normal and pathologic anatomy, added functional information, and an expansion of diagnostic MR imaging applications. Currently, only gadopentetate dimeglumine, a contrast enhancer of the extracellular fluid space that is able to show defects in the blood-brain barrier, is governmentally approved for routine clinical use in North America. An estimated 25%-35% of patients undergoing MR imaging receive this drug. Multiple, potentially competitive formulations have been tested and may soon be approved. In addition, contrast agents differing in purpose and primary magnetic effect, both paramagnetic proton relaxation and magnetic susceptibility agents, are being developed. These include agents for enhancing the blood pool, myocardium, liver, lymph nodes, tumors, and gastrointestinal lumen. Criteria for suitability of new contrast agents include diagnostic efficacy, safety, stability, pharmacology, and cost.

Blood Flow Velocity↗
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

AUR Memorial Award 1991. Immunogenicity of gadolinium-based contrast agents for magnetic resonance imaging. Induction and characterization of antibodies in animals.

To evaluate the immunogenic potential of gadolinium-based magnetic resonance imaging (MRI) contrast agents, Sprague-Dawley rats were sensitized with gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) dimeglumine and with Gd-DTPA covalently linked to either human serum albumin, dextran, or polylysine. IgG antibodies directed against Gd-DTPA were detected in immune sera by an enzyme-linked immunosorbent assay (ELISA), and were confirmed by competitive inhibition of antibody binding using free Gd-DTPA dimeglumine. Antiserum induced by immunization with human serum albumin-(Gd-DTPA) was characterized by a monophasic competition curve with 50% inhibition (IC50) = 5.5 x 10(-4) M when Gd-DTPA dimeglumine was used as both the well-coating and the displacing agent in a competition ELISA. Antiserum induced by Gd-DTPA dimeglumine alone was characterized by a biphasic competition curve with IC50 = 6.5 x 10(-7) M and 7.9 x 10(-4) M. Antisera obtained after exposure to either dextran-(Gd-DTPA) or polylysine-(Gd-DTPA) were of insufficient titer for characterization. The detection of antibodies specific for Gd-DTPA suggests in vivo protein binding with formation of hapten-carrier conjugates. This hypothesis is supported by increased relaxivity values observed when Gd-DTPA dimeglumine is incubated in serum rather than in water. Gd-DTPA dimeglumine and albumin-(Gd-DTPA) are immunogenic in rats under idealized experimental conditions. Additional studies will be necessary to determine the potential for immunologic response in humans to gadolinium chelates under conditions of exposure inherent in clinical use.

Animals↗
PubMed1991

Myocardial infarction: assessment with an intravascular MR contrast medium. Work in progress.

The effect of a new intravascular magnetic resonance (MR) contrast medium (gadolinium diethylenetriaminepentaacetic acid [DTPA] polylysine) was evaluated in acute, subacute, and chronic myocardial infarctions in rats. Signal intensity (SI) was measured before and after intravenous administration of Gd-DTPA polylysine. Before administration of contrast material, chronic infarctions had lower SI than normal myocardium. With Gd-DTPA polylysine, three zones were identified in acute and subacute stages of myocardial infarction, but in the chronic stage, images demonstrated two zones. In acute and subacute infarctions, Gd-DTPA polylysine produced greater enhancement (over 60 minutes) in the peri-infarction zone than in the normal or infarcted myocardium. In chronic infarctions, Gd-DTPA polylysine had no discernible effect on the SI of the central infarction zone. Overall, it caused no significant hemodynamic effects. MR imaging with Gd-DTPA polylysine produced differential tissue enhancement in myocardial infarctions, which varied according to the age of the infarction.

Animals↗
PubMed1991

Differentiation of capillary leak and hydrostatic pulmonary edema with a macromolecular MR imaging contrast agent.

The ability of a macromolecular contrast agent (polylysine-[gadopentetate dimeglumine]40) to allow distinction of pulmonary capillary leak from hydrostatic pulmonary edema was investigated. Capillary leak edema was induced in 12 rats by means of venous injection of oleic acid; hydrostatic pulmonary edema was induced in 10 rats by means of continuous infusion of 0.9% sodium chloride. In the oleic acid pulmonary edema model, the signal intensity continued to increase for 12 minutes after administration of contrast material, indicating a leak of paramagnetic molecules from the intravascular to the extravascular spaces. Conversely, lung enhancement remained virtually constant after injection of contrast material in the hydrostatic edema model, as would be expected in the absence of endothelial damage. Hydrostatic edema tended to be distributed homogeneously throughout the lung, while capillary leak edema tended to occur predominantly in the peripheral portions of the lung. These findings indicate that macromolecular contrast agents can facilitate differentiation between edema caused by elevated intravascular pressure and edema induced by abnormal capillary permeability.

Animals↗