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Biomedical subjects

R C Brasch

Publications and source records attributed to R C Brasch.

At least 91 records · Page 5Linked to original sources
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↗
PubMed1990

Contrast-enhanced magnetic resonance imaging of tumor-bearing mice treated with human recombinant tumor necrosis factor alpha.

Pharmacological effects of recombinant human tumor necrosis factor alpha (TNF) were studied in a mouse fibrosarcoma model using magnetic resonance imaging enhanced with a macromolecular contrast agent, albumin(gadolinium-diethylenetriamine pentaacetic acid)35. TNF was administered i.v. in a dose of 150 micrograms/kg, 60 to 80 min prior to imaging. Contrast-enhanced and nonenhanced magnetic resonance images of TNF-treated (n = 10) and untreated (n = 8) Meth A fibrosarcomas were obtained at 2.0 Tesla using T1-weighted spin-echo pulse sequences. Serial images spanning an interval of 60 to 120 min after TNF administration showed that the TNF-treated tumors enhanced significantly more overall than did untreated tumors (43% versus 31%). The most marked differential tumor enhancement was observed in the tumor rim (59% versus 40%). Nontumorous tissue, including muscle and brain, revealed no significant enhancement differences between TNF-treated animals and controls. The observed tumor enhancement corresponded strongly with Evans blue staining; the TNF-treated tumors stained deep blue, while untreated tumors and normal tissues observed did not stain. The different enhancement and Evans blue staining patterns between TNF-treated tumors and untreated tumors are attributed to TNF-induced changes in tumor capillary integrity. The data indicate that TNF effects on tumors include an increased capillary permeability for macromolecules at early times after administration. The ability to detect changes in capillary permeability in vivo using contrast-enhanced magnetic resonance imaging may prove to be clinically useful to monitor tumor response to TNF.

Animals↗
PubMed1990

Evaluation of Gd-DTPA-labeled dextran as an intravascular MR contrast agent: imaging characteristics in normal rat tissues.

Dextran covalently linked to moieties of gadolinium diethylenetriamine pentaacetic acid (DTPA), for use as a macromolecular, intravascular blood pool marker for contrast material-enhanced magnetic resonance (MR) imaging was characterized by means of physicochemical and relaxivity measurements and MR imaging in healthy rats. Dextran labeled with 15 Gd-DTPA moities (molecular weight of approximately 75,000 d) had a T1 relaxivity at 0.25 T and 37 degrees C of 157.1 mmol-1.sec-1 per molecule and 10.5 mmol-1.sec-1 per gadolinium atom, more than twice that of unbound Gd-DTPA. Osmolality was 300-350 mOsm/kg at a gadolinium concentration of 0.01 mmol/L. Tissue enhancement was essentially linearly related to injected dose in the gadolinium dose range of 0.01-0.05 mmol/kg of body weight. Approximate typical enhancement values over baseline for normal tissues at 10 minutes after a gadolinium dose of 0.05 mmol/kg were as follows: cardiac muscle, adrenal gland, and liver, 40%-50%; lungs, 160%-200%; renal cortex, 130%; renal medulla, 240%; spleen, 75%; muscle, 15%; and brain, 5%-10%. Projection-subtraction images showed that dextran-(Gd-DTPA)15 remained intravascular for at least 1 hour after injection. The prolonged and easily appreciated levels of tissue enhancement with dextran-(Gd-DTPA)15, at a gadolinium dose less than that routinely used in Gd-DTPA, indicate further evaluation of this macromolecular marker.

Animals↗
PubMed1990

Pediatric pulmonary disease: assessment with high-resolution ultrafast CT.

High-resolution computed tomography (HRCT) is widely used to assess pulmonary parenchymal disease in adults. The authors used ultrafast CT with 3-mm collimation and a 100-msec scan time to obtain HRCT scans in 36 children (mean age, 49.4 months). Clinical diagnoses included normal lungs (n = 6), cystic fibrosis (n = 12), obliterative bronchiolitis (n = 6), idiopathic pulmonary hemosiderosis (n = 2), and other lung diseases (n = 10). The HRCT scans and chest radiographs were reviewed separately in blinded fashion. Pulmonary parenchymal abnormalities were categorized into interstitial, airspace, and airway processes. Nine patients with normal chest radiographs had abnormal HRCT scans. In five other patients, the extent of abnormal lung parenchyma was considerably greater on HRCT scans than on chest radiographs. HRCT scans allowed accurate characterization of the type of lung process in 24 of 30 patients when compared with clinical or biopsy findings. Early HRCT findings in cystic fibrosis included lobular air trapping, bronchial wall thickening, and centrilobular nodules. The use of cine CT with high-resolution techniques is feasible in children too young or too sick to hold their breath. HRCT may enable early detection and characterization of pulmonary disease and depiction of the extent of lung abnormality.

Bronchiolitis Obliterans↗
PubMed1990

Albumin labeled with Gd-DTPA. An intravascular contrast-enhancing agent for magnetic resonance blood pool and perfusion imaging.

Paramagnetic macromolecules like Gd-DTPA labeled albumin offer certain beneficial features that distinguish them from smaller molecular paramagnetic contrast media, such as Gd-DTPA dimeglumine, which generally distribute in the extracellular fluid space. By joining multiple paramagnets to one large carrier molecule, the molar dose of the agent necessary for image enhancement is reduced, the proton relaxation effectiveness of such macromolecular agents is increased and they may even serve as markers of perfusion and abnormal vascular permeability. The accumulated experimental results with albumin labeled with Gd-DTPA are described.

Albumins↗
PubMed1989

A model of acute regional myocardial ischemia and reperfusion in the rat.

Studies were conducted in 76 rats to describe and validate a new closed-chest in vivo model for acute ischemia and reperfusion of the left coronary artery. Radiolabeled microsphere distribution in six rat hearts confirmed a significant reduction in arteriolar flow at the center of the ischemic zone (93% reduction of total myocardial counts compared to nonischemic region, P less than 0.01) after 7 min of occlusion. Arteriolar flow returned to control values upon reperfusion. While hemodynamic parameters in 10 rats during 7 min of occlusion and 7 min of reperfusion were monitored, end diastolic pressures increased significantly (P less than 0.01) during occlusion. Finally, the utility of this rat model was demonstrated in a study of contrast enhanced magnetic resonance imaging (N = 4). Normal myocardium could not be differentiated from acutely ischemic myocardium on noncontrast-enhanced MR images. After 5 min of myocardial ischemia and following contrast administration (albumin-Gd-DTPA), the ischemic zone appeared less enhanced than normal myocardium. Upon release of the occluder the left ventricular free wall once again yielded a homogeneous signal similar to that of the normal myocardium.

Animals↗
PubMed1989

Quantitative density-time measurements in the lungs of children with suspected airway obstruction using ultrafast CT.

Fourteen children under 3 years of age with possible airway obstruction were evaluated with an ultrafast CT scanner, Imatron C-100. Serial 0.05-second multilevel scans were obtained through the chest at rates of 17 images per second. No patient sedation or contrast medium was used. Time-density curves generated over each lung and specific pulmonary zones were compared to characterize the normal variation of density during inspiration and expiration and to determine abnormal patterns associated with airway obstruction. There was a high, positive correlation value (r greater than 0.79) between time/density curves over those pulmonary regions in which there was no focal bronchial obstruction and a low, negative correlation value (r = less than -0.58) with bronchial obstruction. Three studies with reconstruction artifacts were excluded. Furthermore, the results indicate that young children generally have denser lungs, particularly in expiration, than older children or adults. This preliminary study suggests that ultrafast CT offers a promising, unique, rapid and noninvasive approach for diagnosing airway obstruction in childhood.

Airway Obstruction↗
PubMed1989

Contrast-enhanced MRI of tumors. Comparison of Gd-DTPA and a macromolecular agent.

The study aim was to define potential differences and advantages in magnetic resonance (MR) patterns of tumoral contrast enhancement using either a small molecular, extracellular fluid contrast enhancer [Gd-DTPA] or a macromolecular agent [albumin-(Gd-DTPA)20], designed for primary intravascular biodistribution. MR images of 25 mice with implanted fibrosarcomas were obtained before and repeatedly for up to 120 minutes after injection of either Gd-DTPA [0.2 mmol/kg, n = 11] or albumin-(Gd-DTPA) [0.0029 mmol/kg, n = 14]. Histologically, this hypovascular tumor contained zones of viable tissue and non-viable, necrotic tissue. Using either type of contrast media, the viable portions enhanced strongly, up to 152% and the necrotic portions enhanced poorly, less than 31%. However, the time-course of enhancement differed between contrast agents. Gd-DTPA tended to provide maximal enhancement soon after administration with no significant changes over two hours. Enhancement from albumin-(Gd-DTPA) was weak initially, corresponding to tumor hypovascularity, but over two hours the signal of the viable tumor zones progressively increased in intensity. This gradual tumoral accumulation of the macromolecular agent within the tumor was considered to reflect abnormal capillary permeability, associated with neovascularity. Thus, the increasing intensity within the neoplastic tissues over time, reflecting abnormal capillary permeability for macromolecules, may serve as a useful, albeit indirect, marker of neoplasia.

Albumins↗
PubMed1989

Ascorbate-induced cancellation of nitroxide contrast media enhancement of MR images.

Ascorbate (Vitamin C), a naturally occurring reducing substance, was tested as an in vivo chemical agent to cancel magnetic resonance imaging (MRI) tissue contrast enhancement induced by a nitroxide spin label contrast agent. Paramagnetic nitroxide compounds can be reduced in vitro by ascorbate to nonparamagnetic hydroxylamine derivatives. A nitroxide agent, TES, was injected intravenously, 2 mmol/kg, in 11 anesthetized rats. Renal cortical and hepatic intensities were monitored by serial T1-weighted images (TR/TE 310/15) acquired precontrast and postcontrast. Fourteen minutes after TES administration, ascorbate (1 mmol/kg) was injected in 6 rats, and saline in 5 control rats. At twenty-nine minutes postcontrast, a second TES-injection was given to all rats. The initial TES-injection resulted in a marked enhancement of kidney cortex and liver. Ascorbate administration immediately cancelled this enhancement. Contrast enhancement could be successfully reinduced by a repeat administration of TES. Results indicate that in vivo administration of reducing agents can be used to immediately cancel enhancement induced by nitroxide contrast media, thus nonenhanced images could be obtained after enhanced images without lengthy delays for contrast media elimination.

Animals↗
PubMed1989

Acute myocardial ischemia and reperfusion: MR imaging with albumin-Gd-DTPA.

The utility of a macromolecular, intravascular contrast agent, albumin-gadolinium diethylenetriaminepentaacetic acid (DTPA), for the differentiation of acutely ischemic and reperfused myocardium on magnetic resonance (MR) images was investigated. Regional, reversible myocardial ischemia was produced in rats and confirmed. After reperfusion, flow to the compromised myocardial segment returned to baseline. Normal myocardium could not be differentiated from ischemic myocardium on nonenhanced MR images (n = 12). After 5 minutes of myocardial ischemia and after administration of albumin-Gd-DTPA, the ischemic zone involving the free wall of the left ventricle was characterized by the absence of significant enhancement. Normal myocardium appeared homogeneously enhanced (by 145%). This pattern persisted for up to 1 hour of myocardial ischemia. In six rats that underwent myocardial reperfusion after 5 minutes of ischemia, the normal and reperfused myocardium became isointense. Radiotracer studies with albumin-Gd-153-DTPA confirmed the decreased distribution of contrast agent to the ischemic myocardium, possibly due to decreased blood pool or a blocked primary delivery system in the ischemic myocardium.

Animals↗
PubMed1989

Cranial bone marrow in children: assessment of normal development with MR imaging.

Magnetic resonance images of cranial bone marrow in 238 patients (246 examinations) less than 25 years old were reviewed to establish normal age-related standards. Bone marrow in the clivus and calvaria had uniformly low signal intensity (grade 1) on T1-weighted images in most infants less than 1 year old. The number of patients with grade 1 marrow decreased rapidly in early childhood, while the number of patients with marrow of low and high signal intensity (grade 2) and uniformly high signal intensity (grade 3) gradually increased with age. A grade 1 marrow was no longer observed in either the clivus or calvaria after age 7. Most patients had a grade 3 marrow by age 15. Because bone marrow in certain pathologic conditions has decreased signal on T1-weighted images and therefore resembles grade 1 or 2 appearances of normal marrow in children, these results may be useful for differentiating normal and abnormal bone marrow signal intensities in infants and children.

Adult↗