1991 in review. Research, leadership, AF relationship.
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Arthritis↗
Biomedical subjects
T J Brady
Publications and source records attributed to T J Brady.
Animal models for magnetic resonance imaging research of the liver.
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Animals↗
Shape of the myopic eye as seen with high-resolution magnetic resonance imaging.
We have obtained multislice magnetic resonance (MR) images of the eye and calculated ocular dimensions along the three cardinal axes: antero-posterior (A-P), equatorial, and vertical. We found no difference in the shape of hyperopic (average refractive error: +3.72 D) and emmetropic eyes, both of which had an equatorial diameter longer than the A-P and vertical diameters. Myopic eyes (average refractive error: -6.54 D) were larger than hyperopic eyes, and most had the same spheroelliptical shape as that of the emmetropic and hyperopic eyes. The results suggest that during myopic progression an overall enlargement or a radial volume expansion has occurred.
Adult↗
Techniques for high-resolution echo-planar MR imaging of the pancreas.
Recent technical advances in echo-planar magnetic resonance (MR) imaging prompted an investigation of these new techniques in pancreatic MR imaging and evaluation of bowel lumen enhancement with an aqueous bowel contrast agent. In 42 subjects (36 healthy, six with pancreatic disease), various T1-weighted inversion-recovery and T2-weighted spin-echo fat-suppressed pulse sequences were assessed with an echo-planar technique implemented with a modified clinical MR imager. Single-excitation imaging (echo time, 26 msec) provided a higher (P less than .05) signal-to-noise ratio than did conventional spin-echo and all other echo-planar techniques. In 13 (72%) of 18 healthy subjects who did not undergo administration of the contrast agent, the entire pancreas was distinguished from adjoining bowel. In all 18 subjects who underwent contrast-enhanced imaging, a significantly greater (P less than .05) intraluminal signal intensity was apparent with all echo-planar pulse sequences and the entire pancreas was identified. In six patients with pancreatic disease, lesions could be identified by their difference in signal intensity.
Barium Sulfate↗
Antimyosin-labeled monocrystalline iron oxide allows detection of myocardial infarct: MR antibody imaging.
The synthesis and in vivo antigen targeting of a novel iron oxide compound were studied. A monocrystalline iron oxide nanoparticle (MION) was synthesized that contains a small (mean diameter, 2.9 nm +/- 0.9) single crystal core, passes through capillary membranes, and exhibits superparamagnetism. The MION was attached to antimyosin Fab (R11D10) and used for immunospecific magnetic resonance (MR) imaging of cardiac infarcts One hour after intravenous administration of MION-R11D10 in rats (100 mumol/kg), a marked decrease in the signal intensity of infarcted myocardium was observed. Immunohistochemical correlation confirmed the specific binding of the immunoconjugate to infarcted, but not to normal, myocardium. No decrease in cardiac signal intensity was observed when unconjugated MION was administered intravenously. The results indicate the feasibility of immunospecific MR imaging in living organisms.
Animals↗
Receptor-directed contrast agents for MR imaging: preclinical evaluation with affinity assays.
In this study, the target-specific behavior of magnetic resonance (MR) imaging contrast agents directed at human hepatic asialoglycoprotein (ASG) receptors was evaluated in vitro with use of two novel assays: relaxation time measurements of incubated human cell membrane solutions and iron staining of biopsy samples. Specific uptake of ASG receptor-directed agents was demonstrated in human samples of normal liver tissue, areas of hepatitis, regenerating nodules, areas of focal nodular hyperplasia, and hepatic adenomas. A conventional iron oxide preparation not directed at ASG receptors failed to demonstrate specific uptake in these tissues. Attachment of the ASG receptor-directed agents was competitively blocked with a receptor agonist (D(+)-galactose) in these tissues. No attachment of conventional or receptor agents was seen in areas of hepatocellular carcinoma, cholangiocarcinoma, or liver metastases. The studies indicate that in vitro receptor assays are useful in predicting the affinity of new receptor-directed MR imaging contrast agents in human tissue prior to clinical trials.
Asialoglycoprotein Receptor↗
Functional mapping of the human visual cortex by magnetic resonance imaging.
Knowledge of regional cerebral hemodynamics has widespread application for both physiological research and clinical assessment because of the well-established interrelation between physiological function, energy metabolism, and localized blood supply. A magnetic resonance technique was developed for quantitative imaging of cerebral hemodynamics, allowing for measurement of regional cerebral blood volume during resting and activated cognitive states. This technique was used to generate the first functional magnetic resonance maps of human task activation, by using a visual stimulus paradigm. During photic stimulation, localized increases in blood volume (32 +/- 10 percent, n = 7 subjects) were detected in the primary visual cortex. Center-of-mass coordinates and linear extents of brain activation within the plane of the calcarine fissure are reported.
Blood Volume↗
MR contrast due to microscopically heterogeneous magnetic susceptibility: numerical simulations and applications to cerebral physiology.
We calculate the effects of subvoxel variations in magnetic susceptibility on MR image intensity for spin-echo (SE) and gradient-echo (GE) experiments for a range of microscopic physical parameters. The model used neglects the overlap of gradients from one magnetic inclusion to the next, and so is valid for low volume fractions and weak perturbations of the magnetic field. Transverse relaxation is predicted to deviate significantly from linear exponential decay in both SE and GE at a particle radius of 2.5 microns. Calculated changes in transverse relaxation rates for SE and GE increase linearly with volume fraction of high-susceptibility regions of 5 microns diameter, but increase with about the 3/2 power of volume fraction of regions with 15 micron spacing between centers. This sensitivity to the actual size and spacing of magnetized regions may allow them to be measured on the basis of contrast. without being resolved in images. GE and SE decay rates are approximately twice as sensitive to long cylinders of 5 microns diameter than to spheres of the same size, for diffusion constants of 2.5 micron 2/ms. Calculated changes in transverse decay rates increase with approximately the square of field and susceptibility variation for 5-microns spheres and a diffusion constant of 2.5 microns 2/ms. This exponent is smaller for cylindrical magnetized regions of the same size, and also depends on the diffusion constant. We discuss possible applications of our theoretical results to the analysis of the effects of high-susceptibility contrast agents in brain. Experimental data from the literature are compared with calculated signal changes according to the model. The monotonic dependence of decay rates on the volume of distribution of the contrast agent suggests that cerebral blood volume and flow could be measured using MR contrast.
Brain↗
Equipment requirements to facilitate contrast-enhanced MR imaging.
During the past decade, MR equipment and imaging techniques have experienced unprecedented development. Significant improvements have been made in image quality, enhancing conventional contrast agent studies. In addition, the development of new applications, such as MR angiography, has expanded the role of existing agents. A major benefit for contrast agent research has been the development of ultrafast MR imaging. This ability to provide information on contrast agent dynamics will aid in the detection and characterization of neoplastic and other disease states. While the gradient-echo techniques may provide adequate temporal resolution for many applications, echo planar imaging will enable the assessment of perfusion for an entire organ, which is critical in the heart or when the location of the pathology is unknown a priori. It is also likely that continued development in MR contrast agents will have a synergistic impact on pulse sequences, e.g., MR diffusion imaging. The growth in functional MR imaging will be based in large measure on the continued interactive development of imaging strategies and magnetopharmaceutials.
Animals↗
Serial magnetic resonance imaging in patients following acute myocardial infarction.
The detection of serial changes in magnetic resonance (MR) signal intensity of the heart following acute myocardial infarction may provide a useful method of characterizing tissue healing. Fourteen patients with acute Q-wave infarction underwent T2-weighted, spin-echo cardiac imaging during hospitalization, followed by one or more additional MR studies (total 31) over a 6- to 27-wk period (mean: 3 mo). Visual assessment of the images demonstrated a gradual reduction in signal intensity and localization of the bright signal to the subendocardium of the infarction region over the three-mo study period. A quantitative measurement of signal intensity (infarction/normal myocardium) fell from 1.81 +/- 0.42 on the initial study to 1.34 +/- 0.37 (p less than 0.05) at a mean of 14 wk. Two patients had an increase in signal intensity on the follow-up study and both patients had been readmitted with acute coronary syndromes. In summary, characterization of changes in signal intensity may provide a useful method of assessing myocardial healing following acute myocardial infarction. Further studies are indicated to determine the prognostic significance of these parameters.
Female↗
Differentiation of bronchogenic carcinoma from postobstructive pneumonitis by magnetic resonance imaging: histopathologic correlation.
Obstructive pneumonitis frequently occurs distal to hilar bronchogenic carcinomas or in lung adjacent to peripheral tumors. The article evaluates the role of MRI in the differentiation of tumor from pneumonitis. Twelve patients underwent MRI of the thorax before surgery. T1-weighted (SE 310/20) and T2-weighted (SE 2000/60-120) images were obtained through the tumor and presumed areas of pneumonitis. Five histologic types of pneumonitis were identified on pathologic examination of the 12 specimens. Cholesterol pneumonitis, found in 7 patients, was the most common type. Organizing pneumonitis, bronchiectasis with mucus plugs, atelectasis, and abscess were found in 3, 4, 2, and 1 patients, respectively. MRI was able to differentiate tumor from pneumonitis in 5 of 6 patients with a hilar mass and in 5 of 6 patients with a peripheral tumor. This was achieved by a visual difference in signal intensity on heavily T2-weighted (SE 2000/120) images. Cholesterol pneumonitis and bronchiectasis with mucus plugs were always hyperintense relative to tumor, and organizing pneumonitis and atelectasis were isointense and indistinguishable from tumor. MRI can differentiate tumor from pneumonitis provided that pneumonitis is of the cholesterol type or if there are mucus plugs in the collapsed lung.
Aged↗
MR imaging of blood-borne liver metastases in mice: contrast enhancement with Fe-EHPG.
To determine whether iron(III)ethylenebis-(2-hydrophenylglycine) (Fe-EHPG), a prototype hepatobiliary magnetic resonance imaging agent, can enhance the liver-to-tumor contrast-to-noise ratio (C/N) in models of liver tumors in mice, two types of cell inoculation were used: intrahepatic implantation of M5076 sarcoma and intrasplenic injection of colon tumor (C-26) or M5076 sarcoma. Significant enhancement of the liver-to-tumor C/N and/or improved visualization of small lesions was consistently observed on T1-weighted images obtained after injection of the contrast material. For intrahepatic implants, the C/N on postinjection T1-weighted images was superior to that on T1- and T2-weighted preinjection images. For the C-26 metastatic liver lesions of larger diameter (greater than 5 mm), the C/N on postinjection T1-weighted studies was superior to that on preinjection T1-weighted images but was comparable to that on preinjection T2-weighted images. However, higher C/N after administration of Fe-EHPG improved visualization of medium-sized (3-5 mm) and small (1-3-mm) metastatic lesions in both M5076 and C-26 models. These results demonstrate that MR imaging with appropriate hepatobiliary agents appears promising for early detection of liver metastases.
Animals↗
Lymph nodes: microstructural anatomy at MR imaging.
High-resolution microscopic magnetic resonance (MR) images of rodent lymph nodes were directly correlated with sections obtained for histologic study to determine the microstructural anatomy of lymph nodes seen at MR imaging and to evaluate signal intensity changes induced by a novel intravenous lymphotropic MR contrast agent (ultrasmall superparamagnetic iron oxide [USPIO]). High-resolution T2-weighted images of unenhanced lymph nodes demonstrated medullary sinus as regions of low signal intensity and follicles as high-intensity structures. After a single intravenous administration of USPIO (160 mumol/kg), both T1-weighted and T2-weighted images showed areas of focal signal intensity loss in medullary sinuses corresponding to the distribution of uptake by macrophages. Lymph follicles appeared unchanged in signal intensity, as they are largely devoid of macrophages. This model of microscopic MR imaging should provide the basis for (a) understanding differences between patterns of contrast-enhanced normal lymph nodes and those of diseased ones and (b) guiding the development of targeting strategies for novel pharmaceuticals at the cellular level.
Animals↗
Asialoglycoprotein receptor function in benign liver disease: evaluation with MR imaging.
An arabinogalactan-coated ultrasmall superparamagnetic iron oxide (AG-USPIO) preparation specific for asialoglycoprotein (ASG) receptors on hepatocytes was used as a magnetic resonance (MR) imaging contrast agent in the evaluation of a spectrum of benign liver diseases in animal models. The activity of hepatocyte ASG receptors, which directly reflects liver function, was directly assessed by measuring liver relaxation times in vitro and MR signal intensity in vivo. The following measurements allowed three-dimensional assessment of liver function: (a) liver relaxation time, (b) native MR signal intensities of liver, (c) response of liver to the AG-USPIO probe (percentage decrease of liver signal intensity after intravenous administration of 10 mumol/kg of AG-USPIO: normal liver 55%, fatty liver 57%, acute hepatitis 36%, chronic hepatitis 29%, and cirrhosis 46%), and (d) redistribution of hepatocyte-specific AG-USPIO to the spleen (present in hepatitis and cirrhosis but not in normal liver and fatty liver). The results of this study indicate that cellular hepatic abnormalities can be detected and quantitated with MR receptor imaging.
Animals↗
Bone marrow: ultrasmall superparamagnetic iron oxide for MR imaging.
An ultrasmall superparamagnetic iron oxide (USPIO) preparation was evaluated as a potential intravenous contrast agent for magnetic resonance (MR) imaging of bone marrow. One hour after administration of USPIO (40, 80, and 160 mumols of iron per kilogram body weight) in rats and rabbits, T1 and T2 relaxation times were, respectively, approximately 30%, 50%, and 65% lower than precontrast relaxation times. Maximum decrease in relaxation times of marrow occurred within 1-24 hours after intravenous administration; thereafter, relaxation times slowly returned to normal within 7 days. In vivo MR imaging of rabbits and rats confirmed that USPIO decreases signal intensity of red and yellow marrow. The decrease was most marked with gradient echo pulse sequences. An animal model of intramedullary tumor demonstrated the potential of USPIO to enable differentiation between tumor and normal red marrow. USPIO-enhanced MR imaging improves detection of smaller tumors and allows differentiation of tumor deposits from islands of hyperplastic or normal red marrow.
Animals↗
Experimental hepatocellular carcinoma: MR receptor imaging.
Relaxation time measurements and magnetic resonance (MR) imaging were performed in three different animal models of hepatocellular carcinoma (HCC). After intravenous administration of asialoglycoprotein-directed arabinogalactan-stabilized ultrasmall superparamagnetic iron oxide (10 mumol Fe/kg receptor agent), T2 of normal liver decreased from 41.6 msec +/- 1.0 to 19.4 msec +/- 1.7 (P less than .05) in rats. T2 of HCC implanted in normal liver or liver with chronic hepatitis was essentially unchanged. These results were similar to those obtained by administration of a reticuloendothelial cell-directed conventional iron oxide; however, the required dose of receptor agent was lower. MR imaging in a woodchuck model of virally induced HCC confirmed the distribution of the hepatocyte-directed agent to regions of functioning and differentiated hepatocytes but not to malignant tumor tissue. The results suggest that MR receptor imaging may play a role in the differentiation between primary liver tumor and functional liver tissue such as that in normal liver hepatitis or regenerating nodules.
Animals↗
Polyclonal human immunoglobulin G labeled with polymeric iron oxide: antibody MR imaging.
Human polyclonal immunoglobulin (Ig) G was attached to a monocrystalline iron oxide nanocompound (MION), a small superparamagnetic probe developed for receptor and antibody magnetic resonance (MR) imaging. The resulting complex, MION-IgG, had a slightly negative surface charge, a molecular weight of 150-180 kDa, and 0.36 microgram of IgG attached per milligram of iron. After intravenous administration of MION-IgG to normal rats, most of the compound localized in liver, spleen, and bone marrow. In an animal model of myositis, MION-IgG caused reduced signal intensity (most apparent on T2-weighted spin-echo and gradient-echo images) at the site of inflammation. No change in signal intensity existed after an injection of unlabeled MION. Site-specific localization of MION-IgG was corroborated with scintigraphic imaging with indium-111 IgG and MION-In-111-IgG and was confirmed histologically with iron staining. These results indicate that antibody MR imaging is feasible in vivo. Target-specific and antibody MR imaging could be easily extended to other applications, including detection of cancer, infarction, and degenerative diseases.
Animals↗
Perfusion imaging with NMR contrast agents.
Knowledge of regional hemodynamics has widespread application for both physiological research and clinical assessment. Here we review the use of MR contrast agents to measure tissue perfusion. Two primary mechanisms of image contrast are discussed: relaxivity and susceptibility effects. Relaxivity effects result from dipolar enhancement of T1 and T2 rates. Because tissue T1 rates are intrinsically smaller, the dominant effect is shortening of T1 relaxation times. The second mechanism of image contrast is the variation in tissue magnetic field produced by heterogeneous distribution of high magnetic susceptibility agents. Quantitation of tissue perfusion requires a detailed understanding of the relation between contrast agent concentration and associated MR signal changes. Studies to date show a linear relationship between contrast agent concentration and rate change in most organs. The exact nature of this relationship in the dynamic setting of rapid contrast agent passage through the microcirculatory bed is less well established. If this relationship is known, tracer kinetic modeling can be used to calculate regional blood flow and blood volume. Data are presented which indicate that this approach is feasible, and suggest the potential of contrast-enhanced NMR for high resolution in vivo mapping of both physiology and anatomy.
Blood Flow Velocity↗