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Biomedical subjects

R C Brasch

Publications and source records attributed to R C Brasch.

At least 109 records · Page 6Linked to original sources

Normal deposition of brain iron in childhood and adolescence: MR imaging at 1.5 T.

Magnetic resonance (MR) images of the brain in 285 patients between the ages of 2 and 25 years were retrospectively studied to determine the appearance of brain iron accumulation. The globus pallidus, red nucleus, substantia nigra, and dentate nucleus were evaluated with long TR/TE (repetition time/echo time) spin-echo sequences and staged. All four regions in most patients were initially hyperintense compared with white matter (stage I) before becoming isointense (stage II) and subsequently hypointense (stage III). The globus pallidus was the first to reach stage III, the red nucleus and substantia nigra were next, and the dentate nucleus was last. In general, decreased signal intensity (stage III) was not seen in these regions in patients less than 10 years old; in most patients it was seen by age 25 years. The dentate nucleus decreased in signal intensity more slowly and inconsistently; only one-third of patients had reached stage III by age 25 years. The temporal sequence of normal iron deposition as detected with MR imaging is helpful not only in the diagnosis of known iron-deposition diseases but also in the detection of iron-related pathologic changes.

Adolescent↗

Cerebral Erdheim-Chester disease: persistent enhancement with Gd-DTPA on MR images.

A case of Erdheim-Chester disease with intracerebral masses containing characteristic lipid-laden histiocytes is presented. These unusual lesions remained enhanced on magnetic resonance images obtained 8 days after injection of gadolinium diethylenetriaminepentaacetic acid (DTPA) dimeglumine. Chemical analysis of a biopsy specimen revealed a high concentration of gadolinium. Findings suggest that the Gd-DTPA complex or possibly a gadolinium-containing metabolite may be retained for extended periods in this unusual type of histiocytic lesion.

Brain↗

Assessment of myocardial salvage after ischemia and reperfusion using magnetic resonance imaging and spectroscopy.

To test the hypothesis that contrast-enhanced magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) can differentiate reversible from irreversible myocardial injury, these modalities were used to study ischemia and reperfusion in a rat model. The presence of ischemia and reperfusion were confirmed with radiolabeled microspheres (n = 6). Groups of animals were subjected to either 16 (n = 17), 30 (n = 14), 60 (n = 11), or 90 (n = 14) minutes of left coronary artery (LCA) occlusion and 60 minutes reperfusion. After albumin-gadolinium (Gd)-DTPA injection, contrast-enhanced, T1-weighted, spin-echo proton images were acquired at baseline and every 16 minutes during LCA occlusion and reperfusion. In separate experiments, 31phosphorus (31P) spectra were acquired at similar time points during ischemia and reperfusion. After 16 minutes occlusion, normally perfused myocardium enhanced significantly compared with ischemic myocardium on MRI (104 +/- 7.9% vs. 61 +/- 11.0%, p less than 0.05, n = 5, mean +/- SEM, % of baseline value). MRS showed reduced phosphocreatine (PCr) and adenosine triphosphate (ATP) (58.8 +/- 2.4%, p less than or equal to 0.01; 81.4 +/- 2.4, p less than or equal to 0.01, n = 12). After 16 or 30 minutes ischemia, reflow resulted in uniform MRI signal intensity of the ischemic zone compared with normal myocardium (93.5 +/- 11.3 vs. 80.9 +/- 7.0, p = NS, n = 11, % of baseline value at 30 minutes reperfusion) and PCr recovery on MRS (94.3 +/- 4.0%, p = NS, n = 20, % baseline value at 30 minutes reflow). After 60 and 90 minutes ischemia, reflow resulted in marked enhancement of reperfused compared with normal myocardium on MRI (254.0 +/- 30.0 vs. 78.3 +/- 9.2, p less than or equal to 0.01, n = 10) and no recovery of PCr on MRS (64.1 +/- 3.0, p = NS, n = 14). Triphenyltetrazolium chloride (TTC) staining revealed transmural myocardial infarction (MI) in all hearts subjected to 60 or 90 minutes ischemia and reflow, and small nontransmural MIs in only 2/11 hearts subjected to 16 or 30 minutes ischemia and reperfusion. Thus, 1) MRI with albumin-Gd-DTPA is useful for identifying myocardial ischemia by enhancing the contrast between normally perfused and ischemic myocardia; 2) MRI with albumin-Gd-DTPA is useful for identifying reperfusion after myocardial ischemia; and 3) after reperfusion, reversible can be distinguished from irreversible myocardial injury by characteristic findings on MRI and MRS.

Albumins↗

[Specific and non-specific contrast media for MRI of tumors. Experimental study of human breast carcinoma].

MRI has been shown as an adapted non-invasive modality for the detection of tumours in humans. The development of paramagnetic contrast agents could add to the MRI diagnosis. With an experimental model of human breast (MX-1) carcinoma developed in nude mice, two different classes of contrast medium were tested. The first class includes the well-known Gd-DTPA and a new nitroxide compound on going development, representing non specific contrast agents. The specific contrast agents are represented by a metalloporphyrin Mn-TPPS4. Non specific contrast agents can add to the differentiation between well vascularized viable tissue and necrotic areas of tumors. While specific contrast agents may specifically target tumorous tissue.

Animals↗

Pharmacokinetics in the rat and the dog of a nonionic nitroxide contrast agent for magnetic resonance imaging.

Nitroxides are paramagnetic stable free radicals that have demonstrated effectiveness as contrast agents in proton magnetic resonance imaging (MRI). The pharmacokinetics and metabolic fate, determinants of the time course of MRI contrast enhancement, of a new nonionic pyrrolidine nitroxide derivative, TAP (2,2,5,5-tetramethylpyrrolidine-1-oxyl-3-carbonic acid-(2,3-dihydroxy-1-hydroxymethyl)-amide), were evaluated in the rat and the dog. A biexponential decline of the blood concentration of TAP was observed in both species after intravenous administration of 0.1- and 2.5-mmol/kg doses. The clearances in the rat, estimated after the low and high doses (15.4 +/- 2.0 and 15.3 +/- 1.4 mL/min.kg, respectively), were about twofold higher than those observed in two beagles (7.4 and 7.1 mL/min.kg for Dog #1 and 6.3 and 6.0 mL/min.kg for Dog #2). The hydroxylamine of TAP, formed by a one-electron reduction of the nitroxide moiety, was the only metabolite observed. This bioreduction of TAP has implications for its use as a MRI contrast agent because the diamagnetic hydroxylamine lacks contrast enhancing activity. In both animal species, the urinary recoveries of the dose as unchanged TAP and its hydroxylamine were essentially complete for the 24-h urine collections (92 to 98% and 83 to 95% for the rats and the dogs, respectively). Anticipated conjugative metabolism of the hydroxyl-containing side chain of TAP was not observed. Renal excretion of unchanged TAP was the predominant route of elimination, as renal clearance was estimated to be between 47 and 89% of total clearance in the dogs. Bioreduction in vivo was slower than that expected from the observed reduction of TAP in vitro in ascorbic acid solution and in rat liver and kidney homogenates.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Experimental acute pancreatitis: MR relaxation time studies using gadolinium-DTPA.

Spin-lattice (T1) and spin-spin (T2) relaxation times of normal and sodium taurocholate-induced pancreatitis (38 rats) were determined in vitro using a 10.7-MHz magnetic resonance (MR) spectrometer. The increase in pancreatic T1 time in acute hemorrhagic pancreatitis correlated well with the elevated water content of the organ. Gadolinium-DTPA did not affect significantly the relaxation times of normal pancreas in vitro during 1 t 20 min postinjection, but it decreased the elevated T1 times of inflamed pancreas almost to baseline values. MR imaging studies of rat pancreas in vivo (8 rats, 0.35-T resistive magnet) indicated that the swollen pancreas and associated edema were depicted using a T2-weighted SE sequence. Fifteen minutes postinjection of gadolinium-DTPA a homogeneous enhancement of inflamed pancreas was detected. The differentiation of pancreatic necrotic foci from surrounding viable tissue and edema could not be detected on Gd-DTPA-enhanced MR images after 15 min postinjection although microscopical workup indicated these different tissue constituents in the pancreas.

Acute Disease↗

MR imaging of liver abscesses; application of Gd-DTPA.

The potential utility of Gd-DTPA contrast enhancement of MR images in the evaluation of liver abscesses was assessed in rodents. Twelve rats with surgically implanted sterile liver abscesses were imaged at various stages of focal hepatic inflammation, 48 hours, 4 days, 7 days, 14 days and 21 days after lesion induction. Spin echo images, acquired before and repeatedly after intravenous injection of 0.2 mmol/kg Gd-DTPA, demonstrated improvement of the lesion-to-background contrast ranging from 2% to 40% depending on the stage of the disease. The enhancement pattern also varied with abscess evolution. Two, four and seven-day-old abscesses typically showed a ring enhancement, whereas two- and three-week-old abscesses presented largely homogeneously enhancing lesions. In the earlier lesions, contrast enhanced rim surrounding the low intensity center corresponded histologically to the formation of a capsule consisting of fibrous tissue and inflammatory cells. The center was necrotic. Data show that abscesses can be detected on images acquired with long repetition and echo times without injection of Gd-DTPA. The administration of Gd-DTPA, however, improved the lesion-to-background contrast and helped to define the abscess capsule evolution.

Animals↗

Pyrroxamide, a nonionic nitroxyl spin label contrast agent for magnetic resonance imaging. Mutagenesis and cell survival.

Pyrroxamide [N-(1-hydroxymethyl-2,3-dihydroxypropyl)-2,2,5,5-tetramethyl pyrrolidine-1-oxyl-3-carboxyamide] is a newly tested nonionic monomeric nitroxyl compound with demonstrated effectiveness for MRI contrast enhancement at doses as low as 10(-3) M. Pyrroxamide and its hydroxylamine metabolic derivative were tested in concentrations from 10(-9) to 10(-2) M with a battery of cytotoxic and mutagenic assays using mammalian Chinese hamster ovary cells. Loci-specific mutation induction was examined at the hypoxanthine-guanine phosphoribosyltransferase (HGPRT) and the Na+/K+ ATPase loci, both in the presence and absence of a liver microsomal metabolic activating mixture (S-9 mix). Cell survival and induction of sister chromatid exchanges also were studied. All tests yielded negative results indicating that pyrroxamide and and hydroxylamine derivative were both noncytotoxic and nonmutagenic at the doses tested.

Animals↗

Ultrafast computed tomography for infants and children.

Experience using ultrafast CT in the diagnostic evaluation of more than 50 infants and children indicates that this new technique is highly accurate and easily performed. Ultrafast CT offers several advantages compared to conventional CT. Scan times of either 0.05 or 0.1 seconds were sufficiently short to eliminate motion artifacts, even without patient sedation; sedation is a routine procedure for the conventional CT examination of most infants and small children and carries a finite risk. Procedure time appears to be shorter using ultrafast CT, 15 minutes or less, than with conventional CT. No control data using conventional CT are available for this patient population, but generally pediatric body CT studies are scheduled at hourly intervals at our medical center and are rarely completed in less than 30 minutes. Dynamic imaging alternatives for evaluation of the pediatric heart and airway include angiocardiography, digital subtraction studies, and fluoroscopy, which are limited by relatively high radiation exposure and by the inability to display all wall motions simultaneously due to their projectional rather than tomographic orientation. The potential for acquiring serial 0.05-second images of rapidly moving structures, including the heart, airway, and lungs, is unique to the ultrafast CT technique and facilitates the identification of functional abnormalities, including intracardiac shunts, valvular obstructions, tracheomalacia, and segmental bronchial obstruction. The relationships of mediastinal soft tissue structures and vessels are well defined by both ultrafast and conventional CT. In situations in which fine spatial resolution is pivotally important, the radiologist has the option with the C-100 scanner to select the 0.1-second scanning mode. This mode results in a higher radiation exposure per slice, approximately two-fold, and also uses an array of more closely spaced detectors, 864, to increase dose efficiency and spatial resolution. Although not generally required for our pediatric patients, one has the additional option of performing repeated 0.1-second images at any level, as many as ten exposures, totaling 1.0 seconds, to increase photon flux and increase resolution. Thus, the choice of scanning options can markedly influence both radiation dose, resolution, and contrast sensitivity characteristics.

Child↗

Metabolic fate in the dog of the nitroxide moiety in a compound with potential utility as a contrast agent in MRI.

Nitroxides, paramagnetic compounds with demonstrated effectiveness as contrast agents in proton magnetic resonance imaging, shorten the relaxation times of protons and therefore cause an increase in image intensity in tissues into which they distribute. In this study, the metabolic fate of the nitroxide moiety was examined in the dog using a pyrrolidine nitroxide derivative, 2,2,5,5-tetramethylpyrrolidine-1-oxyl-3-carboxylic acid, for which contrast-enhancing properties have been previously studied in animals. After radiolabeling by microwave discharge in the presence of tritium gas, the compound was administered intravenously to a dog. Ninety-four percent of the radioactivity injected was recovered in urine within 3 days; the majority (90%) was excreted during the first 6 h. The radioactivity in the urine was identified as either the unchanged nitroxide or its corresponding hydroxylamine. Neither complete reduction of the nitroxide moiety to the amine nor any other metabolic transformation was observed.

Animals↗

Gadolinium-DTPA enhanced MR imaging of intramuscular abscesses.

Sterile, chemical and bacterial abscesses were induced in the paraspinal muscles of 16 rats before obtaining magnetic resonance (MR) images using a 0.35-T resistive system. Abscess intensity, T1 and T2 values were recorded before and after the intravenous administration of Gd-DTPA (0.2 mmol/kg). The MR appearances of the abscesses were correlated with histologic sections. Both sterile and bacterial abscess were detected on MR images without the use of contrast medium, particularly on the T2-weighted spin echo sequence (TE/TR 56/2000 ms). However, the inflammatory zones of abscesses markedly enhanced in intensity with a corresponding decrease in T1 values after the administration of Gd-DTPA (TE/TR 28/500 ms). A clear distinction between the necrotic center and the cellular periphery of each abscesses was evident only after contrast enhancement (TE/TR 28/500 ms). Thus paramagnetic Gadolinium-DTPA was beneficial for defining the histologic components of abscesses on spin echo MR images.

Abscess↗

Aerosolized gadolinium-DTPA enhances the magnetic resonance signal of extravascular lung water.

Gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA), a contrast agent for magnetic resonance imaging, was administered by either aerosol or intravenous injection to rats. Proton relaxation times in excised lungs and kidneys were then measured. With increasing concentrations of aerosolized Gd-DTPA, the spin-lattice relaxation time (T1) of lungs decreased (enhanced) significantly (P less than .001), an effect that persisted for at least 80 minutes; there was no change in kidney T1. After intravenous injection of Gd-DTPA, lung T1 did not change, but kidney T1 decreased significantly (P less than .001), confirming previous observations of renal clearance. It is concluded that aerosolized Gd-DTPA is a more efficacious method of delivery of paramagnetic contrast agent to the lungs than intravenous injection, and that the lack of systemic effect after aerosolization indicates that enhancement was limited to the extravascular compartment.

Administration, Inhalation↗

Magnetic resonance imaging of myocardial infarction using albumin-(Gd-DTPA), a macromolecular blood-volume contrast agent in a rat model.

Magnetic resonance (MR) contrast enhancement of acute myocardial infarction was studied in rats using albumin-(Gd-DTPA), a paramagnetic macromolecule with prolonged intravascular retention after intravenous injection. Histologic examination and distribution measurements of radiolabeled microspheres confirmed induction of regional myocardial infarction after ligation of the left coronary artery. ECG-gated spin-echo images at 2.0 Tesla, employing short, T1-weighted pulse sequence settings, demonstrated time-persistent and significant (P less than .05) enhancement of normal myocardium (66%) and an even greater enhancement of the infarcted area (100%), for as long as 60 minutes after injection of 160 mg/kg albumin-(Gd-DTPA). The contrast difference between normal and infarcted myocardium was increased significantly (P less than .05) after administration of albumin-(Gd-DTPA). The prolonged enhancing effects of albumin-(Gd-DTPA) on MR images are useful for evaluating regional differences in blood volume and capillary integrity between normal and infarcted myocardium.

Animals↗

Magnetic resonance imaging of experimental renal hemorrhage.

Experimental renal hemorrhage was induced by injecting autologous blood into the left kidney of 13 rats. To investigate the magnetic resonance (MR) characteristics of acute renal hemorrhage and subsequent stages of resolution, repetitive MR images were obtained using a 0.35 Tesla imager during a period of 21 days postinduction. A dual spin-echo imaging (TR 500 and 2,000 msec, TE 28 and 56 msec) was used to calculate the relaxation times and record the intensities in the renal medulla and cortex. Histologic examination (n = 9) indicated that blood was dispersed intrarenally, and no encapsulated hematoma developed. The signal intensity on the T1- and T2-weighted images, as well as the relaxation times in the hemorrhagic renal parenchyma were unchanged during 21 days when compared with intact kidney values. Subcapsular fresh blood had a high signal intensity on T2-weighted images. A marked overlap of the relaxation parameters between intact kidney parenchyma and diffuse intrarenal hemorrhage was observed. Detection of dispersed intrarenal blood using spin echo MR imaging may be difficult.

Animals↗

Metalloporphyrin contrast enhancement of tumors in magnetic resonance imaging. A study of human carcinoma, lymphoma, and fibrosarcoma in mice.

The diagnostic use of Mn(III)TPPS4, a paramagnetic metalloporphyrin, for MR contrast enhancement was examined in human--mouse xenograph models of carcinoma, lymphoma, and sarcoma. Spin-echo images of 15 mice, five mice for each implanted tumor type, were obtained before and at 20 minutes, and 2, 4, and 24 hours following administration of 0.09 mmol/kg of Mn(III)TPPS4. All tumors had a uniform moderate signal intensity on precontrast images. After administration of Mn(III)TPPS4, all tumors demonstrated significant enhancement of signal intensity that persisted to 24 hours. T1 relaxation times were maximally depressed at 2-4 hours and remained low to 24 hours for all three tumors. Kidney signal intensity reached a maximum at 20 minutes and remained significantly above background for 24 hours. The high relaxivity and apparent avidity of Mn(III)TPPS4 for divergent tumor histologies support the potential use of this agent for improved diagnostic specificity of MR imaging for neoplastic masses.

Animals↗

Albumin labeled with Gd-DTPA as an intravascular, blood pool-enhancing agent for MR imaging: biodistribution and imaging studies.

Albumin is a macromolecule that remains largely confined to the vascular space after intravenous administration. Human serum albumin was paramagnetically labeled by covalently binding from nine to 18 gadolinium-DTPA (diethylenetriaminepentaacetic acid) chelates per protein molecule. This conjugate was tested in varying doses for in vivo biodistribution and effectiveness in tissue relaxation. After intravenous injection of the agent in rats, T1 relaxation times were significantly reduced in samples of the blood and in lung, heart, spleen, kidney, and brain tissue. These effects persisted at a relatively constant level for the next 30 minutes. In vivo magnetic resonance imaging of the heart and lungs of rats and rabbits confirmed the prolonged contrast-enhancing effect of the labeled albumin. These preliminary studies indicate that paramagnetically labeled macromolecules that distribute in the intravascular space may be effective for MR imaging evaluation of tissue blood volume.

Animals↗

Upper airway obstruction in infants and children: evaluation with ultrafast CT.

The diagnostic accuracy of ultrafast computed tomography (CT) was evaluated prospectively in 25 infants and children with suspected airway obstruction. All examinations were conducted in spontaneously breathing, nonsedated children. Scan acquisition times were 0.05 or 0.1 second. CT examinations, completed in an average of 10 minutes, routinely included localizing, contiguous sections through the trachea followed by serial images obtained at a rate of 17 per second through regions of interest. Imaging results were correct in 24 of 25 examinations as judged from clinical and surgical data. Ultrafast CT data permitted diagnosis of dynamic changes in airway caliber, small intraluminal polyps, focal tracheal atresia, compressive mediastinal masses, and foreign body obstructions of the major bronchi. Dose measurements showed a maximum skin exposure of 245 mR (0.06 mC/kg) per 0.05-second image. Ultrafast CT provides an accurate, minimally invasive method for dynamic imaging of the airway in nonsedated children.

Adolescent↗