A new gadolinium-based contrast agent for magnetic resonance imaging of brain tumors: kinetic study on a C6 rat glioma model.

T1-weighted magnetic resonance imaging (MRI) was used to evaluate the potential interest of a new Gd-based contrast agent, termed P760, to characterize brain tumor heterogeneity and vascularization and to delineate regions containing permeable vessels. The C6 rat glioma model was used as a model of high-grade glioblastoma. The signal enhancement was measured as a function of time in the vascular compartment and in different regions of interest (ROIs) within the tumor after the injection of 0.02 mmol x kg(-1) of P760. The results were compared to those obtained after the injection of 0.1 mmol x kg(-1) of Gd-DOTA. We showed that P760, in spite of a Gd concentration five times smaller, produces an enhancement in the blood pool similar to that produced by Gd-DOTA. It was shown that P760 makes possible an excellent delineation of regions containing vessels with a damaged blood-brain barrier (BBB). Images acquired 5-10 minutes after P760 injection showed the location of permeable vessels more accurately than Gd-DOTA-enhanced images. The enhancement produced in the tumor by P760 was, however, less than that produced by Gd-DOTA. The extravasation and/or diffusion rate of P760 in the interstitial medium were found to be strongly reduced, compared to those found with Gd-DOTA. This study suggests that the new contrast agent has promising capabilities in clinical imaging of brain tumors.

In vivo measurement of the size of lipid droplets in an intracerebral glioma in the rat.

Pulsed field gradient NMR was used to measure the root mean square displacement lambda of the NMR visible lipid molecules in C6 brain tumors in the rat at different diffusion times. For a distribution of spherical droplets of diameter with volume fraction xi(Phi(i)), the mean characteristic droplet diameter Phi(c) = square root of Sigma(i)xi(Phi(i)Phi(i)(2) was shown to be related to the root mean square displacement at long diffusion times by the simple relationship Phi(c)(2) = 10 lambda(2). In the range of diffusion times 100--530 msec, lambda was found to be independent of the diffusion time and equal to 1.35 +/- 0.22 microm and Phi(c) to 4.27 +/- 0.71 microm. The data reinforce the notion that the presence of lipid resonances in NMR spectra of tumors is due to lipid droplets. Light microscopy of histologic slices showed the presence of lipid droplets mainly in the necrotic region and in a layer of tumor cells surrounding the necrosis. Magn Reson Med 45:409-414, 2001.

Evidence that mobile lipids detected in rat brain glioma by 1H nuclear magnetic resonance correspond to lipid droplets.

Mobile lipids have been detected by proton nuclear magnetic resonance (NMR) in animal and human tumors (cultured cells, biopsies, and in vivo), but their origin and subcellular location are still unclear. They have been associated with malignancy, metastatic ability, drug resistance, and necrosis. We wanted to determine whether these lipids are located within plasma membrane microdomains or in lipid droplets for a C6 cell-induced rat glioma. NMR-visible mobile lipids were found in all subcellular fractions isolated from the rat tumor, except in the cytosolic supernatants. Transmission electron microscopy showed that lipid droplets were present in all subcellular fractions containing NMR-visible lipids and in the necrotic and perinecrotic areas of the tumor. The mean diameter of droplets isolated by flotation in the subcellular fractionation protocol was 0.97 microm (n = 682; droplet profile diameter range between 0.2 and 5.0 microm). The apparent diffusion coefficient for these lipids (46 +/- 17 microm2 s(-1) measured in vivo by proton spectroscopy was four orders of magnitude higher than would be expected if mobile lipids were inside plasma membrane microdomains. The combined results demonstrated that mobile lipids detected in vivo by proton NMR in the C6 rat glioma are located in large lipid droplets, associated with the necrotic process.

Proton spectral editing in the inhomogeneous radiofrequency field of a surface coil using modified stimulated echoes.

It is shown that the modified stimulated echo sequence, [theta](+/- x +/- y)-t1-[theta](+ x)-t2/2-[2 theta](+ x)-t2/2- [theta](+ x)-t1-Acq(+/- x +/- y), denoted as MSTE[2 theta]x according to the exciter phase of the 2 theta pulse, is able to perform proton spectral editing without difference spectra. On the other hand, this sequence appears to be suitable for spatial localization. Sensitivity and spatial selectivity of MSTE and conventional stimulated echo sequence (STE) are briefly compared. MSTE is applied to editing lactate in the rat brain using the locally restricted excitation of a surface coil.

Self-referencing subtractive angiography by modified stimulated echo in magnetic resonance imaging.

In magnetic resonance imaging, the modified stimulated echo sequence (MSTE) method significantly reduces the signal from stationary nuclei. This sequence was successfully applied to transverse imaging, improving the contrast of moving materials. With the results reported here, it will be shown that projective angiography using MSTE is also feasible without the usual subtraction of two separated images. Another advantage is selectivity with respect to velocity.

Modified stimulated echo sequence for elimination of signals from stationary spins in MRI.

Simple modification of the basic stimulated echo sequence (MSTE), including bipolar gradient modulation, permits one to generate relative motion phase modulations between the two STE magnetization components. It is shown how this self-referencing process can provide flow enhancement without combination of separated images.