J. Chambron

Distinct patterns of active and non-active plaques using texture analysis on brain NMR images in multiple sclerosis patients: preliminary results

The benefits of texture analysis of magnetic resonance images have been assessed in multiple sclerosis (MS) patients. Out of thirty-two lesions identified in eight MS patients, nine were considered active, judging from their gadolinium uptake. Texture analysis allowed to obtain forty-two characterizing parameters for each lesion. Using discriminant analysis as a statistical method allowed to classify the lesions into two groups: active or non-active. An attempt to classify their level of activity by using only co-occurrence matrices was unsuccessful. Alternately, the same type of analysis performed on runlength analysis criteria allowed the accurate classification of 88% of active lesions and 96% of non-active lesions. Using incremental discriminate analysis can reduce the number of useful parameters. This method showed that among the 42 parameters, 8 only were highly significant and permitted an accurate classification. Five of these parameters are runlength parameters, and three others are more directly related to the global distribution. The main interest of runlength parameters is that they allowed to demonstrate that the lesion structure was different in active and non-active plaques. This preliminary work suggests that using texture analysis could be of interest in the follow-up of MS patients because it provides an opportunity to identify active lesions without frequent gadolinium injections.

Existence of contralateral abnormalities revealed by texture analysis in unilateral intractable hippocampal epilepsy

We selected 23 patients with unilateral temporal lobe epilepsy characterized by ipsilateral hippocampal sclerosis and an apparently normal contralateral hippocampus on MR imaging. Images were acquired on a 0.28 T MR scanner using a conventional Carr-Purcell Meiboom Gill sequence in all patients and in 9 healthy subjects. Texture analysis was applied to axial MR images of the first and tenth echoes. Texture analysis detects macroscopic lesions and microscopic abnormalities that can not be observed visually. The presence of texture differences in the between normal (controls) and sclerotic hippocampi was ascertained by statistical discriminant analysis. The apparently normal contralateral hippocampi can be classified into three categories in terms of texture: 4 apparently healthy, 8 similar to sclerosis, and 11 different from either healthy or sclerosis. These findings are related to a certain degree of hippocampal alteration, which further investigation might help better characterize.

Oxygen imaging in perfused hearts by dynamic nuclear polarization

The feasibility of localized oximetry by dynamic nuclear polarization (DNP) imaging is demonstrated on perfused sheep hearts. DNPI is a magnetic, double resonance technique, in which the electron paramagnetic resonance (EPR) of a free radical dissolved in a perfusion medium is saturated, while the nuclear magnetic resonance (NMR) of water protons is used to perform conventional NMR imaging. The presence of oxygen reduces the enhancement of the NMR signal induced by DNP. The oxygen content of sheep heart tissues was detected by the subtraction of the DNP image of the heart, perfused with a nitrogen-equilibrated solution, from an image obtained when the heart was perfused with an oxygen-equilibrated solution. This result was obtained with extreme oxygen partial pressure, and the discussion presents physical and chemical means for improving the DNP imaging method. Physical means include field cycling, electron paramagnetic rotary saturation, and the use of a 180 degrees NMR pulse before EPR irradiation. The chemical means discussed are deuterium substitution in nitroxides and the potential use of solid, free radical probes. It is suggested to use the perfused heart model for comparing the numerous methods available to measure the oxygen content of tissues.

Photoacoustic detection of triplet state and singlet oxygen in highly absorbing samples

Abstract— A photoacoustic (PA) effect theory taking into account two heat sources corresponding to the radiationless relaxation processes of two states of different lifetimes and to the heat diffusion across the sample is herewith presented. Results obtained demonstrate that the amplitude and the phase of the PA signal depend on the samples thermal properties, on its optical absorption coefficient, on the lifetime of the long‐lived excited state, and on the ratio of the two heat sources. This ratio can be expressed as a function of the product of the energy of the excited state times the quantum yield of its production. Simulations of PA amplitude and phase variations vs light modulation frequency exhibit new features of the PA signal: phase inversion and fast decrease of the amplitude. Experimental verifications were carried out on solutions and gels. Fitting of the amplitude and phase variations allow us to measure the lifetime and conversion yield of the intermediate state which can be a triplet state or singlet oxygen, O2(1Δg). The addition of an acceptor, specific to O2(1Δg), induces changes in the amplitude of the PA signal which can be used to study the production and deactivation of this excited form of oxygen. This work demonstrates the usefullness of PA in the detection of metastable excited states such as the triplet state and singlet oxygen and in their quantitative analysis.

Magnetic resonance imaging of antibody-mediated demyelinating experimental allergic encephalomyelitis.

Two models of demyelinating experimental allergic encephalomyelitis (EAE) were studied on Lewis rats in whom the disease was induced by injections of either (i) lentil-lectin binding myelin glycoproteins plus myelin basic protein (MBP)-specific T cells (36 rats), or (ii) myelin/oligodendrocyte glycoprotein-specific monoclonal antibody plus MBP-specific T cells (16 rats). In our 24 control rats, 20 received MBP-specific T cells only, and four received myelin glycoproteins plus purified protein derivative-specific T cells. The extent of the resulting blood-brain barrier (BBB) permeability, vasogenic oedema and/or demyelination was assessed in vivo using magnetic resonance imaging (MRI) techniques. The results show that in both demyelinating EAE models the disease appeared more quickly, progressed very rapidly and was more severe than when induced with a similar number of MBP-specific T cells alone. Almost all animals developed hyperacute EAE, with a very high mortality rate. MRI showed a very intense BBB breakdown and vasogenic oedema in all the normally leaky areas of the central nervous system, and focal lesions corresponding to plaque formation in the brain stem or spinal cord near the leaky areas. During the 40-day observation period, the rare survivors of this hyperacute form of EAE presented a chronic form of EAE with serious sequelae. Our results demonstrate that the synergistic effect observed between MBP-specific T cells and antibodies to myelin glycoproteins, especially to myelin/oligodendrocyte glycoprotein, does not only induce demyelinating lesions and chronic clinical signs, but is further responsible, via the normally leaky areas, for the fatal increase of the BBB breakdown and vasogenic oedema of which there are ample acute clinical signs.

Detection of late epilepsy by the texture analysis of MR brain images in the lithium-pilocarpine rat model

The aim of the study was to detect by texture analysis non easily visible anomalies of magnetic resonance (MR) images of piriform and entorhinal cortices relevant to the lithium-pilocarpine (Li-Pilo) model of temporal lobe epilepsy in rats. Status epilepticus was induced by Li-Pilo in twenty male rats 21 day-old. T(2)-weighted MR images of their brain, were obtained before injection of Li-Pilo and one day after status epilepticus. An hyperintense signal was found in the piriform and entorhinal cortices of six rats, which developed chronic epilepsy after a latent period of one to three months. Among the 14 other rats which displayed images similar to those obtained before injection, four remained healthy but 10 rats developed late epileptic symptoms, raising the problem of hidden cortical damage which may be too subtle to be detected by classic MRI examination. A numeric treatment of digital images was then undertaken by texture analysis, to derive image information from a purely computational point of view. The combined texture and discriminant analyses based on pixels pattern anomalies, selected 3 texture parameters derived from co-occurrence matrix which characterized structural abnormalities relevant to the hyperintense signal, not only in the modified images of 6 rats but also in images of 10 rats with apparently non modified images. These three textures parameters allowed to classify the twenty rats of our experiment as follows: sixteen epileptic rats were effectively classified with cortical lesions, two non epileptic were correctly classified with healthy cortex, but two healthy rats were not correctly classified. This misclassification is discussed on the basis of the time dependence of the onset of seizure in the Li-Pilo model. These promising results suggest to apply this method to MRI examinations for an improvement of the early diagnostic of human epilepsy.

An evaluation of the significance of areas of intense signal in the MR brain images of patients with multiple sclerosis

This study evaluates the distribution of areas of intense signal (AIS) in 189 patients with multiple sclerosis (MS) and 83 patients presenting high-risk factors of cerebrovascular injuries. Two multivariate statistical analyses (multifactorial discriminant analysis and logistic regression analysis) with two AIS scores and several subpopulations of patients (according to age and/or the number of AIS) were tested. The results of these analyses were expressed with the usual screening test. The results obtained in this study even without the help of any clinical information are very promising, since they established that the specificity of MRI could be improved by using the distribution of the AIS in the various anatomical areas as a criterion. Five regions of the brain display were particularly significant in the discrimination between MS and non-MS patients: In decreasing order we found that the temporal, occipital, brain stem, and parietal regions were more specific with respect to the diagnosis of MS, while only the basal ganglia could account for non-MS patients. With multifactorial discriminant analysis and logistic regression analysis respectively, 78.9 (+/- 2.8)% and 85.1 (+/- 2.8)% of the patients were correctly classified by MRI. The results obtained on the main group were confirmed by a predictive test carried out on an other population of 40 patients, which produced similar results. The comparison between our method and Fazekass imaging criteria showed a 20% improvement in favour of our approach and it is hoped that it will contribute to make the most of MRI as a tool for the diagnosis of MS.

Proton nuclear magnetic resonance relaxation rates in aqueous solutions of amino acids

Variations of water-proton NMR relaxation rates induced by amino acids are very different for longitudinal and transverse relaxations. The presence of amino acids increases the longitudinal relaxation rate only slightly, when compared with the increase induced by the oxygen content of the solution. The measured transverse relaxation rate is dependent on the pulse delay of a Carr-Purcell-Meiboom-Gill sequence. Transverse proton relaxation dispersions are shown to be consistent with rapid proton exchange between water and the NH+ 3 groups of the amino acids. The mean exchange time is about 1 ms. The variation of the exchange time with temperature yields the enthalpy and the entropy of the apparent first-order reaction of this exchange. Changes of pH, temperature and oxygen content give rise to opposite effects on relaxation rates of amino acid solutions. The discussion here underlines the fact that, even in such a simple system, relaxation-rate measurements give valuable information only if the physico-chem...

Susceptibility-based MRI contrast of the CSF by intravascular superparamagnetic nanoparticles

Endorem®, a suspension of superparamagnetic iron oxide dextran nanoparticles (NP), have been injected intravenously to healthy anesthetized rats for the purpose of contrast enhancement of brain in gradient-echo imaging at 200 MHz. Not only gray and white matter but also particular regions of the cerebrospinal fluid (CSF) were contrasted in sagittal and transverse images, although samples of this fluid did not contain NP. The selected contrast in the CSF would result from the ability of dense vascular beds containing highly magnetized particles to induce a remote susceptibility effect far beyond the vascular walls into a large fraction of extravascular water.

Viscosity of water in hibernating and nonhibernating mammals estimated by proton NMR relaxation times

Longitudinal (T1) and transverse (T2) nuclear magnetic resonance relaxation times were measured in vitro at 37, 30, 25, 15, and 5 degrees C on serum, brain, liver, kidney, and heart samples from a hibernator, the European hamster, active in summer (SA), active in winter, or in the hibernating state in winter; from a less efficient hibernator, the golden hamster; and from a homeotherm, the rat. T1 and T2 relaxation times varied between species and in the European hamster between the active and hibernating subjects. Despite the major relaxation time differences between the organs, NMR relaxation time measurements showed a general trend to an increase in the viscosity of water for the European hamster in the active state. Although these modifications were not directly related to the process of hibernation itself, the relaxation times observed in the hibernating animals were closer to those seen in the rat. This evidenced that changes of physical properties of water reflect a better adaptation to low temperatures of the hamster, as compared to the nonhibernator, given that the low water viscosity of SA hamster allows the decrease of the viscosity with temperature during the hibernating state. These in vitro studies permit the study the viscosity which is an important physicochemical parameter involved in NMR longitudinal relaxation time of water proton. More detailed studies of other physiological parameters must be undertaken by further in vivo measurements.