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Magnetic resonance imaging detects blood-brain barrier disruption after gadolinium-DTPA enhancement of central nervous system lesions of multiple sclerosis. Experimental allergic encephalomyelitis has many clinical and pathological features in common with multiple sclerosis including alterations in the integrity of the blood-brain barrier. We have compared T2-weighted cranial MR images with Gd-DTPA dimeglumine-enhanced T1-weighted images of myelin basic protein-induced acute (Days 8-42 postimmunization) and central nervous system-induced chronic-progressive (Days 70-95 postimmunization) forms of experimental allergic encephalomyelitis in the guinea pig. Although animals from both groups had abnormal T2-weighted images, only the myelin basic protein-acute-EAE animals (Days 14-24 postimmunization) showed enhancement on postcontrast MR studies. The different responses of the acute and chronic diseases may result from different immunogens, severity of disease, or different permeability of the blood-brain barrier. Therefore, gadolinium-DTPA-enhanced, T1-weighted MR images distinguish acutely active and chronic inflammatory lesions in experimental allergic encephalomyelitis.

Two phospholipids—one bearing a nitroxide free radical covalently attached to its polar headgroup, and the other bearing a similarly attached chelating agent with bound gadolinium—were compared in vivo as liposomal contrast agents for MR imaging. In each case the phospholipid contrast agent was incorporated into the membranes of sonicated unilamellar vesicles. The agent with bound gadolinium proved to be considerably more potent at highlighting regions of liposome biodistribution than did its spin-labelled analogue. Injected intramuscularly into rats, the spin-label liposomes produced local tissue contrast that persisted for 1 h; while under similar conditions, the liposomal gadolinium persisted for over 24 h. By comparison, water-soluble, nonliposomal DTPA-Gd3+ (dimeglumine), was rapidly cleared from the same intramuscular sites—appearing in kidney and bladder within 15 min of injection. When delivered intravenously, maximum effect from both liposomal agents was observed in liver and spleen within 1–2 h, although the spin-label agent produced only marginal contrast. The concomitant use of fat suppression proved a valuable adjunct to liposomal contrast for imaging organs of the reticuloendothelial system. © 1991 Academic Press, Inc.

To determine the factors which may alter NMR relaxation times in multiple sclerosis (MS) lesions we measured the proton T1 and T2, specific gravity (SG), and histology in the central nervous system (CNS; 13–19 levels per animal) in the myelin basic protein (MBP) and CNS-induced acute and relapsing EAE models in 44 juvenile Hartley guinea pigs. In the MBP model, T1 is unchanged but T2 is prolonged before symptoms and pathological changes occur. T2 remains prolonged during the acute phase of MBP-in-duced EAE. In the acute CNS model, T1 and T2 were not different from control despite advanced pathological changes of inflammation and demyelination and changes in specific gravity, indicating a marked change in tissue water content. No single variable, pathological or SG, could predict TI or T2 values in the CNS-induced model. In active disease in the MBP model, when edema occurs in the presence or absence of parenchymal infiltration, T2 values are increased. However, as the factors which influence tissue NMR characteristics are complex in these MS models, it is likely difficult to infer specific pathological events from MRI findings in patients with MS. © 1990 Academic Press, Inc.

Gadolinium-DTPA enhanced magnetic resonance (MR) imaging has been used to demonstrate uterine vascular changes during ovoimplantation and artificially induced decidualization in rats. Evans blue dye and Gd-DTPA were injected i.v. into rats 10 h after unilateral decidualization was induced by injection of sesame oil into the lumen of one uterine horn. Animals were killed various times later and uteri were removed, T1-weighted proton imaging was performed, and mean image intensities for stimulated and control uterine horns were calculated by computer-assisted image analysis. Macroscopic bluing confined to stimulated horns was apparent 5 min after tracer injection and increased in intensity until the experiment was terminated at 320 min. Analysis of MR images showed that mean image intensity of control horns did not change significantly at any time after injection of the Gd-DTPA and Evans blue whereas mean image intensity of stimulated horns increased significantly by 5 min after injection, peaked at 20 min, and returned to values not different from controls by 320 min. T1-weighted images of day 6 pregnant rats injected with Gd-DTPA and Evans blue revealed patterns of image enhancement that matched those of macroscopic bluing. Uterine concentrations of radioactivity after injection of 153Gd-DTPA indicated that increased extracellular fluid volume (ECFV) produces the image enhancement of stimulated horns since the tracer permeates the extracellular fluid of both horns. Gd-DTPA-enhanced MR imaging of uteri after deciduogenic stimulation revealed significant image enhancement for stimulated horns at both 9 and 27 h after stimulation. We conclude that Gd-DTPA enhanced MR imaging allows the identification of uterine vascular changes during ovoimplantation and decidualization and that this methodology may be useful in both experimental and clinical settings.

This paper describes the facilities successfully used to provide patient monitoring and anesthesia support in a 1.5-T imaging installation. The requirements for the MRI site for anesthetic gases, shielded power, and radiofrequency ports are outlined. Specific modifications in anesthesia machines, anesthesia cart, laryngoscope, mercury sphygmomanometer, oximeter, and remote blood pressure devices are described. Additional aspects of patient monitoring and support, e.g., electrocardiogram and pressure infusion, are also discussed.

Given current clinical use of phospholipid bilayer structures (liposomes/vesicles) as non-toxic drug delivery vehicles, we have addressed the possibility of employing the phospholipids themselves as MRI contrast agents. To this end we have synthesized phosphatidylcholine with a nitroxide spin label replacing one methyl residue of the choline headgroup. This material was mixed with natural phosphatidylcholine in mole ratios from 150 to 1:1 and used to prepare sonicated unilamellar vesicles in saline. Expected structural features of these vesicles were verified by freeze-fracture electron microscopy. Proton T1 values of saline were readily decreased to less than 0.3 s by such preparations, yielding a net relaxivity of 0.6 M−1 s−1. The approach seems to be a realistic way of firmly associating a contrast agent of minimal toxicity with ordinary liposomes/vesicles in a manner that is not subject to leakage. © 1987 Academic Press, Inc.

Differences in the tissue properties of water are the basis for the detailed anatomic visualization of internal body structures produced by NMR imaging. Physiological and pathological events have the potential to alter proton nuclear magnetic resonance relaxation properties through changes in water environment. In this study, the parenteral injection of pharmaceuticals produced significant changes (12-21%) in proton NMR relaxation times in tissues of treated rats. The extent of relaxation time change was both tissue specific and drug specific. Therefore, the effects of common pharmaceuticals should be considered in the interpretation of T1- and T2-weighted NMR images.

The age of sensitization determines the clinical course of experimental allergic encephalomyelitis (EAE) in the guinea pig. Adult animals immunized with central nervous system (CNS) tissue develop acute, fulminant EAE, whereas a relapsing-remitting illness resembling multiple sclerosis occurs if sensitization occurs in the first 2 weeks of life. This study characterized the changes in the proton nuclear magnetic resonance (NMR) relaxometry and imaging of the CNS during the immediate postnatal period. T1 and T2 relaxation times in cerebral hemispheres and spinal cords of strain 13 guinea pigs were consistently prolonged at birth, progressively shortened in the first few weeks of life, and achieved adult levels by age 6 to 11 weeks. There were no age-dependent differences in T1 and T2 relaxation times and tissue specific gravity in either strain 13 or Hartley guinea pigs following immunization with complete Freund's adjuvant, an agent previously reported to disrupt the blood-brain barrier to IgG and albumin in strain 13 guinea pigs. The CNS of neonatal guinea pigs appeared well myelinated by light microscopy and there was no apparent difference in the extent of myelination between newborn and adult animals. Although it was possible to distinguish gray from white matter in the cervical spinal cord of newborn guinea pigs by magnetic resonance imaging (MRI) techniques, gray/white contrast was less satisfactory in the cerebral hemispheres until approximately 6 weeks of life when it was possible to differentiate gray matter, white matter, and cerebrospinal fluid. This study indicates that NMR relaxation times change during early postnatal life, at a time corresponding to the unexplained differences in susceptibility to an immune challenge. These developmental changes appear to be independent of the degree of CNS myelination.

In guinea pigs immunized with myelin basic protein (MBP) in complete Freund's adjuvant, experimental allergic encephalomyelitis (EAE) shows a characteristic clinical and pathological course. This study characterized the proton nuclear magnetic resonance (NMR) properties of the central nervous system prior to the onset of clinical signs of EAE. At this time (Days 7–9), the blood brain barrier is disrupted. The effects of the injection of paramagnetic contrast agents gadolinium-DTPA and gadolinium-deferoxamine on the tissue NMR relaxation times were examined. Both proton T1 and T2 relaxation times were prolonged in the spinal cord and the brain prior to the onset of clinical and pathological changes. The largest change was in the thoracolumbar spinal cord where T2 prolongation was 22.9%. Gadolinium-DTPA produced a moderate (5-11%) or marked (9-19%) decrease in control and MBP-treated animals, respectively. Gadolinium-deferoxamine also decreased proton relaxation times but was toxic to all animals, producing respiratory arrest. Changes in proton T2 relaxation times in cord and cerebellum were sufficiently large (> 10%) to suggest that they might be visualized by magnetic resonance imaging techniques. We have previously described the changes in proton relaxation times during the acute phase of EAE (S. J. Karlik, G. Strejan, J. J. Gilbert, and J. H. Noseworthy, Neurology36, 1112 (1986)). This study indicates that proton relaxation times are significantly altered at a time when blood brain barrier disruption occurs prior to the onset of clinical or pathological signs. © 1987 Academic Press, Inc.

We investigated in vitro NMR properties of bleomycin-induced alveolitis and pulmonary fibrosis in 18 Lewis rats (6 controls). When alveolitis or fibrosis had developed, animal lungs were excised and examined histologically and gravimetrically and their T1 and T2 were determined by a NMR spectrometer at 10.7 MHz and 37 degrees C. Clinical diagnosis was confirmed histologically in each case. The NMR signal intensities were significantly elevated in both disease states (P less than 0.001). Both T1 and T2 values of alveolitic lungs were about the same as in controls, but were significantly decreased in fibrotic lungs (P less than 0.01). Changes in T1 and T2 correlated well (P less than 0.001) with changes in water content of diseased lungs.