Magnetic resonance imaging for pediatric diagnosis.
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Biomedical subjects
Publications and source records attributed to R C Brasch.
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A paramagnetic-labeled macromolecule, albumin-(Gd-DTPA), was prepared for use as an intravascular contrast agent for magnetic resonance imaging. An average of 19 Gd-DTPA chelates were covalently conjugated to human serum albumin through the bifunctional anhydride of DTPA. The albumin-(Gd-DTPA) was characterized with use of high-performance liquid chromatography, sodium dodecyl sulfate gel electrophoresis, atomic absorption, biuret and Bradford protein tests, and by its effect on proton relaxation (relaxivity). The average molecular weight was 92,000 daltons, indicating the albumin conjugate was predominantly monomeric. The T1 relaxivity of albumin-(Gd-DTPA) was 273 mM-1 sec-1 relative to carrier concentration, which corresponds to a relaxivity of 14.9 mM-1 sec-1 relative to gadolinium concentration. The average conditional stability constant for albumin-bound Gd-DTPA chelate was log K = 20.0. Spin-echo images of rats demonstrated persistent enhancement of vascular tissues and slowly flowing blood. Application of albumin-(Gd-DTPA) may augment the MR assessments of blood volume, tissue perfusion, and flow characteristics.
Nitroxyl spin labels are paramagnetic compounds that have demonstrated utility as contrast enhancing agents in proton magnetic resonance imaging. The time-course of contrast enhancement depends on distribution and elimination of these agents. Reduction, resulting in formation of the diamagnetic hydroxylamine, is the major metabolic pathway observed in vivo. This bioreduction has implications for the design of contrast agents and for understanding their imaging behavior. Bioreduction has been shown to occur, at least in part, intracellularly. As such, cell membrane permeability to nitroxyl spin labels may influence their bioreduction. In this study, this influence was examined using eight nitroxyl derivatives and the human erythrocyte suspension as a model biomembrane system. Ionizable weak acids and bases were found to equilibrate rapidly across the erythrocyte membrane with half-times of equilibration ranging from less than 10 s to 1.6 min. These derivatives had low octanol:buffer distribution coefficients and were extensively ionized at the pH of the system (7.0). A strong acid, a phosphate ester, and a quaternary amine derivative were excluded by the cell membrane. Reduction of nitroxyl spin labels by the erythrocyte was shown to occur intracellularly. Except for the impermeable probes, the reduction rate was slow in comparison with the membrane penetration rate. The structural dependence of reduction rate was unrelated to penetration rate but correlated well with that observed in other reducing systems, namely, ascorbic acid solution and rat tissue homogenates.
This study was to determine if manipulation of magnetic resonance signal intensity by means of an intravenously injected paramagnetic contrast agent is useful for the detection and characterization of periarticular inflammation. Arthritis was induced in 20 rats by means of intradermal injection of Freund's complete adjuvant. MR imaging was performed with a resistive magnet operating at 0.35 T. A double spin-echo technique with TE's of 28 and 56 ms and TR's of 0.5 and 2.0 s was used. The hindpaws of the adjuvant-injected rats were imaged on Day 8, Day 11, or Day 15 following injection of the adjuvant. The images were obtained in the transverse plane before and after intravenous injection of gadolinium-DTPA (0.2 mmol/kg). Because of their long T2 relaxation time, inflammatory lesions were characterized by high MR signal intensity on precontrast images obtained with long TR and long TE (T2-weighted images). On the other hand, because of their long T1 relaxation time, the inflammatory lesions were of relatively low intensity and not easily recognized on precontrast images obtained with short TR and short TE (T1-weighted images). Postcontrast T1-weighted images were also sensitive in detecting periarticular inflammation as a result of T1 shortening by the gadolinium-DTPA. However, in our particular model, the data did not indicate any greater MR sensitivity for detecting arthritis by means of gadolinium-DTPA enhancement.
Magnetic resonance imaging (MRI) is a promising new diagnostic modality that is well suited for the evaluation of children with hematological or oncological diagnosis. The side effects of ionizing radiation are avoided, the tomographic pathological anatomy in three orthogonal planes can be obtained, and differences between normal and abnormal tissues are often present. In order to present our preliminary clinical experience with MRI in pediatric hematology and oncology, the historical background of MRI, the technique, and possibilities for tissue characterization are reviewed.
Preliminary clinical experience with magnetic resonance imaging (MRI) in 28 pediatric patients with 20 different hematological diseases, benign tumors, or malignant neoplasms is presented. The clinical results are presented in the form of case presentations that are discussed in the context of alternative diagnostic imaging modalities. Also discussed are the known biological effects, or lack thereof, the need for sedation, the effect of motion, the effect of MRI on foreign metallic objects, the financial considerations, and the trends for the future of MRI. This imaging modality has many unique merits. Present difficulties should be overcome by future innovations, making MRI even more efficacious for the diagnosis of blood diseases and cancer in children.
Changes in contrast due to paramagnetic substances depend on many factors, such as the properties and concentration of the substance, the external pulse and time parameters and the inherent relaxation time of the tissues. The physical background for contrast enhancement by paramagnetic substances is reviewed and the various groups of magneto-pharmaceuticals which have been used experimentally and clinically are described. The effect on signal intensity due to changes in dose, pulse sequence, repetition and echo times have been simulated and measured on phantoms and the effect of various tissue relaxation times on contrast has been investigated.
The proton relaxation enhancement characteristics of seven potential MRI contrast agents containing two nitroxyl spin labels per molecule (diradicals) were compared with eight similar agents with only one spin label per molecule (monoradicals). Diradical nitroxyls were evaluated to test the hypothesis that multiple paramagnetic centers in one molecule will result in stronger proton relaxation enhancement characteristics, allowing effective contrast enhancement at lower molar concentrations and thus a reduced osmotic load and greater safety. The acute toxicity of these agents is believed to be largely related to osmotic load. Five of seven diradical nitroxyls tested had spin-lattice relaxivities that were substantially greater than all eight of the monoradicals tested. The spin-spin relaxation properties of these agents and other pertinent characteristics are favorable for contrast enhancement. The results indicate that diradical nitroxyl spin labels may be used advantageously for the design of safer, more effective MRI contrast agents.
Gadolinium-DTPA (Gd-DTPA) enhancement of magnetic resonance (MR) imaging was tested for diagnostic utility in evaluating carcinoma. Human breast carcinoma implanted in ten nude mice was studied before and after injection of Gd-DTPA at two different doses (0.2 and 0.5 mmol/kg body weight). Before injection, all tumors appeared homogeneous in intensity on spin-echo images; after injection, it was possible to distinguish areas of strong enhancement from areas of weak enhancement. Histologic correlations showed that the strongly enhanced areas corresponded to richly vascularized connective tissue and apparently viable tumoral tissues, while the weakly enhanced areas corresponded to nonvascularized necrotic tissue. The results indicate that intravenously administered paramagnetic agents such as Gd-DTPA may improve the specificity and diagnostic accuracy of MR imaging by permitting better differentiation of tumor elements.
The effects of a paramagnetic contrast agent, gadolinium-DTPA (Gd-DTPA), on magnetic resonance (MR) imaging of acute cerebral ischemia was investigated in a feline model of middle cerebral artery occlusion. Imaging was performed both before and after administration of an intravenous dose of 0.2 mmol/kg of Gd-DTPA. The animals were then sacrificed for pathologic correlation. No changes in intensity or relaxation times were noted before or after Gd-DTPA administration in two animals with 2 hours of occlusion. Infarcts were noted before and after contrast enhancement in all six cats with ischemia of greater than 16-hours duration. Gd-DTPA caused significant increase in intensity of infarct but not in that of normal cerebral tissue. Rapid enhancement was visible in infarcts of 16-24 hours, but such enhancement was slower in infarcts of 72-168 hours, presumably owing to slowed inflow caused by increased vasogenic edema in the latter group. Contrast enhancement of acute cerebral ischemic lesions with Gd-DTPA offers no improvement in sensitivity of MR imaging, although the conspicuity of the lesion may be improved. Additionally, contrast media may provide potential temporal and pathophysiological data for better characterization of cerebral ischemia.
Studies were performed to determine the possible influence of physiologic motion on the parenchymal intensity of organs in magnetic resonance (MR) images. It is known that periodic motion associated with respiration and cardiac function causes characteristic artifacts in spin-warp images. The present study shows that bulk motion can also cause striking intensity changes at velocities equivalent to the craniocaudal respiratory excursion of organs in the upper abdomen. The magnitude of the effect depends on the velocity and direction of motion with respect to the three orthogonal axes of the imager and on the technical details of the imager and pulse sequence. Large systematic errors in calculated tissue relaxation times are possible due to this phenomenon. The findings have important implications for clinical imaging because motion can cause artifactual changes in the gray-scale relationships among tissues. Some pulse sequences are much less sensitive to these effects. These results provide guidance for selecting MR techniques that reduce the detrimental effect of respiratory and other physiologic motion on examinations of the upper abdomen and thorax.
Magnetic resonance imaging of the lumbar spine was performed in 17 children with acute lymphocytic leukemia (ALL): eight with newly diagnosed ALL, four with ALL in relapse, and five with ALL in remission. Eleven age-matched children were also imaged as controls. The T1 and T2 relaxation times of the bone marrow in the lumbar spine were calculated for all the children. The T1 relaxation times of the bone marrow were as follows (mean +/- standard deviation): newly diagnosed ALL, 968 msec +/- 68; ALL in relapse, 765 msec +/- 19; ALL in remission, 404 msec +/- 135; and age-matched controls, 441 msec +/- 82. T1 relaxation time was statistically significant in differentiating children with newly diagnosed ALL from normal children and from children with ALL in remission. In addition, T1 may be useful in differentiating children with ALL in relapse from children with ALL in remission and from healthy children. T2 was not significantly different among the four groups.
Albumin-(gadolinium-diethylenetriaminepentaacetic acid), albumin-(Gd-DTPA), a macromolecular MR contrast agent designed for intravascular distribution, was compared with gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA), an extracellular fluid agent, for imaging characteristics in normal rats at 2.0 T. Albumin-(Gd-DTPA) produced larger-intensity increases in myocardium (125%), liver (114%), and brain (21%), at a dose of 0.062 mmol Gd/kg than did Gd-DTPA at a dose of 0.2 mmol/kg. The duration and pattern of enhancement differed between the two compounds; the enhancement with albumin-(Gd-DTPA) persisted at relatively constant levels from 2 min to 1 hr. The Gd-DTPA tissue enhancement peaked at 2 min and had virtually disappeared at 60 min. Gd-DTPA better enhanced subcutaneous tissues, presumably because of capillary permeability and enhancement of the abundant extracellular fluid space. When albumin-(Gd-DTPA) is used, the strong persistent enhancement of the microvascular compartment is well demonstrated on subtracted images and supports potential application of albumin-(Gd-DTPA) for blood-volume and perfusion-dependent contrast enhancement of myocardium, liver, and brain.
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A child receiving unilateral pulmonary radiation therapy for metastatic Wilms' tumor in early childhood was noted to develop gradually an asymmetrical thorax. This was clinically diagnosed as scoliosis but radiographs indicated pulmonary hypoplasia as the true cause.
The experience from 123 pediatric MRI examinations disclosed several different types of artifacts and age-related variants that could have caused pitfalls in MRI interpretation. Artifacts were caused by metallic objects, patient touching the RF coil, and patient motion. The potential pitfalls are caused by the MRI variant appearances of anatomical structures specific to the growing body. Recommendations concerning preparation and immobilization of children prior to and during MRI examinations to minimize artifacts are given.
Delineation of the gastrointestinal tract in magnetic resonance imaging (MRI) remains a problem. Ferric ammonium citrate is paramagnetic, producing a high MRI signal intensity by virtue of its spin-lattice (T1) relaxation rate enhancement properties. Water is diamagnetic, producing a low MRI signal intensity, especially with short TR and TE times. To compare efficacy for gastrointestinal contrast alteration, ferric ammonium citrate was administered to 18 patients and water was given to 10 patients. Spin-echo imaging at 0.35T was performed after administration of these agents. Ferric ammonium citrate produced high signal intensity within the esophagus, stomach, duodenum, and small intestine that aided in the differentiation of the gastrointestinal tract from adjacent tumors, vessels, and viscera. Delineation of the gut wall was superior using ferric ammonium citrate compared to that produced by water. Delineation of the margins of the pancreas, liver, and kidney from adjacent gastrointestinal tract was also better with ferric ammonium citrate. Optimal distinction between bowel and fat was better with water. Longer TE times (75 to 200 ms) may allow improved contrast between gut and intrabdominal fat using ferric ammonium citrate.