NMR investigation of experimental chemical induced brain tumors in rats, potential of a superparamagnetic contrast agent (MD3) to improve diagnosis

The different steps of development of chemically induced brain tumors were investigated in rats by MRI using a superparamagnetic contrast agent, magnetite-dextran nanoparticles (MD3). Sprague-Dawley strain pregnant female rats were injected intravenously with ethynitrosourea solution at the end of pregnancy. Offspring whelped by the inoculated mother were followed. MRI examinations were performed at 0.5 T. MD3 nanoparticles were injected intravenously at a dose of 5 mg Fe kg^-1 body weight 30 min before rat sacrifice. After sacrifice, histological slices were stained with hematoxylin-eosin. Relaxation times were measured at 40 MHz and 37°. MD3 nanoparticles act differently according to the step of the tumor development. Before tumor appearance, at a step characterized by the presence of abnormal cell clusters, relaxation time T2 increased significantly. The T2-weighted image showed a small increase in signal intensity in the lesion. Image contrast was improved by MD3 nanoparticles injection because of the decrease in healthy tissue signal intensity. The Tl-weighted image did not provide any additional information. In presence of a minute tumor, relaxation times decreased in tumor but increased in surrounding tissue. The Tl-weighted image showed a hypersignal on the border of an hyposignal. T2-weighted image showed a hypersignal in the same area. Signal intensity was not modified after MD3 nanoparticles injection. When new vascular capillaries developed in the tumor, MD3 nanoparticles cross into the cerebral parenchyma. Transmission electron microscopy showed magnetite crystals in this specific area on cytoplasm vesicles of glial cells and in tumor-specific membrane arrangements. On T2-weighted image, the hypersignal consisted of a well defined part and a second more fuzzy part, its signal being extinguished after MD3 nanoparticles injection. Necrotic areas and edema can be discriminated. The use of such a superparamagnetic contrast agent would be helpful in early detection of tumor development and in improving distinction of tumor mass from its vascular environment in patients. © 1998 Elsevier Science B.V. All rights reserved.     

Turbo spin-echo sequences in magnetic resonance imaging of the brain: Physics and applications

Fast SE imaging provides considerable measure time reduction, high signal-to-noise ratios as well as similar contrast behavior compared to conventional SE sequences. Besides TR and TE_eff, echo train length (ETL), interecho time , and-space trajectory determine image contrast and image quality in fast SE sequences. True proton density contrast (CSF hypointense) and not too strong T2 contrast are essential requirements in routine brain MRI. A Turbo SE sequence with very short echo train length (ETL=3), short TE_eff and short interecho time (17 ms), and TR=2000 ms was selected for proton density contrast; a Turbo SE sequence with ETL=7, TE_eff=90 ms, =22 ms, and TR=3250 ms was selected for T₂-weighted images. Using both single-echo Turbo SE sequences yielded 50% measure time reduction compared to the conventional SE technique. Conventional SE and optimized Turbo SE sequences were compared in 150 patients resulting in very similar signal and contrast behavior. Furthermore, reduced flow artifacts in proton density—and especially in T₂-weighted Turbo SE images—and better contrast of high-intensity lesions in proton density-weighted Turbo SE images were found. Slightly reduced edge sharpness—mainly in T₂-weighted Turbo SE images—did not reduce diagnostic reliability. Differences between conventional and Turbo SE images concerning image contrast and quality are explained regarding special features of fast SE technique.Address for correspondence: Institut für Röntgendiagnostik, Klinikum der Universität Regensburg, Franz-Josef-Strauß-Allee 11, 93042 Regensburg, Germany. Additional reprints of this chapter may be obtained from the Reprints Department, Chapman & Hall, One Venn Plaza, New York, NY 10119.     

Transient global brain ischemia in young and aged rats: differences in severity and progression, but not localisation, of lesions evaluated by magnetic resonance imaging

A model of transient global brain ischemia consisting of bilateral occlusion of common carotid arteries for 10 min and mild hypoxia (15% O₂−85% N₂) for 20 min was studied by means of MRI in young and aged Fischer 344 rats (3–4 and 24–26 months, respectively). Ischemia was assessed by full suppression of spontaneous EEG activity, which reappeared and normalized similarly in the two age-groups. The survival of young with respect to aged rats was considerably higher both at 24 h (20/20, i.e. 100% vs 12/16, i.e. 75%) and at 48 h (16/20, i.e. 80% vs 6/16, i.e. 38%). The localisation of brain lesions, their severity and progression were evaluated by a diffusion-weighted MRI (DWI) sequence at 24 and 48 h post-ischemia. There were no DWI-detectable lesions in eight out of 20 young and two out of 12 aged rats. The localisation of DWI-detected lesions was rather similar in rats of the two age-groups. In fact, the cerebral cortex, mainly parietal, occipital and temporal lobes were damaged in 83% of young and 90% of aged rats. The respective percentages for the thalamus were 83 and 60%, for the striatum 58 and 50%, and for the hippocampus 25 and 30%. The lesions present in the cerebral cortex and the thalamus were considerably more severe in aged than in young rats. In conclusion, in spite of similar localisation of ischemic lesions in the two age-groups, their incidence was higher, appearance more rapid and severity more pronounced in aged with respect to young rats. This resulted in a considerably higher mortality of the former. The overall data indicate that the age issue is very important in experimental ischemia research.     

Assignment of the 2.03 ppm resonance in in vivo <Superscript>1</Superscript>H MRS of human brain tumour cystic fluid: contribution of macromolecules

MRI and MRS are established techniques for the evaluation of intracranial mass lesions and cysts. The 2.03 ppm signal recorded in their ¹H-MRS spectra is often assigned to NAA from outer volume contamination, although it has also been detected in non-infiltrating tumours and large cysts. We have investigated the molecular origin of this resonance in ten samples of cystic fluids from human brain tumours. The NMR detected content of the 2.03 ppm resonance in 136 ms echo time spectra, assuming an N- CH₃ origin, was 3.19 ± 1.01 mM. Only one third (34 ± 12%) of the N-acetyl containing compound (NAC) signal could be extracted by perchloric acid (PCA) indicating that most of it originated in a macromolecular PCA-insoluble component. Chemical analysis of the cyst fluids showed that sialic acid bound to macromolecules would account for 64.3% and hexuronic containing compounds for 29.2% of the NMR-detectable ex vivo signal, 93.4% of the signal at TE 136 ms. Lactate content measured by NMR (6.4 ± 4.4 mM) and the predominance of NAC originating in sialic acid point to a major origin from tumour rather than from plasma for this 2.03 ppm resonance.