Lysolecithin-induced demyelination in primates: preliminary in vivo study with MR and magnetization transfer.

PURPOSE: To study bystander demyelination in multiple sclerosis with an experimental in vivo model of toxic demyelination. METHODS: Toxic demyelinating lesions were created in two monkeys by injection of lysophosphatidylcholine in the centrum semiovale. Follow-up was done clinically and with serial MR studies, including T2-weighted and gadolinium-enhanced T1-weighted images and measurement of magnetization transfer ratio, until the animals were killed at days 14 and 34, respectively. Light and electron microscopy analysis was compared with MR data. RESULTS: Interval measurement of magnetization transfer ratio during the course of the experiment revealed a maximum decrease at day 7 to day 8, associated with the greatest clinical manifestations. The lowest values of magnetization transfer ratio correlated with histopathologic findings of myelin and axon destruction. Magnetization transfer ratio measurements appear to be sensitive to macromolecular destruction and specifically to membrane disorganization. At no time was gadolinium enhancement observed in this model of toxic demyelination. CONCLUSION: Preliminary results of this study indicated that magnetization transfer is a good technique to follow in vivo matrix destruction in brain parenchyma lesions. The results suggest also that phases of toxic demyelination in multiple sclerosis might not show gadolinium enhancement. Differentiation between demyelinating activity and associated inflammation in multiple sclerosis lesions should be considered in further in vivo work.

Effects of nimodipine on posttraumatic spinal cord ischemia in baboons.

Posttraumatic ischemia appears to be largely responsible for the extension of lesions in acute injury of the spinal cord. In the present study, we have evaluated the putative improvement of axonal function by the calcium channel blocker nimodipine after acute trauma of the spinal cord. Three techniques were used: (1) spinal cord blood flow (SCBF) using a scanographic technique with stable xenon, (2) somatosensory evoked potentials (SEPs), and (3) magnetic resonance imaging (MRI). Thirteen baboons were used in this study. Acute trauma was achieved by compression of the spinal cord at level L1 by applying pressure for 5 sec with an inflated balloon catheter injected with Ringer's solution. Following the injury, one group (n = 5) received a saline infusion (placebo) for seven days, and a second group (n = 8) received a nimodipine infusion (0.04 mg/kg/h) during the same period of time. SCBF and SEP were first recorded prior to trauma. SCBF, SEPs, and MRI were then recorded on the day of the injury and eight days prior to histologic examination of the spinal cord. In these studies nimodipine significantly improved SCBF. The decrease in SCBF observed at day one and day eight following trauma was significantly reduced in the treated group. Two baboons in the treated group also showed improvement of axonal function as assessed by SEP. No significant difference was observed with MRI, however, histologic study revealed that the lesions were significantly smaller in the treated group. Based on these observations we conclude that a week of nimodipine treatment following spinal cord injury enhances SCBF, limits the size of the spinal cord lesion, and perhaps improves functional recovery.

[Methods for measuring spinal cord blood flow]. / Méthodes de mesure du débit sanguin médullaire.

This study aimed to review the techniques used most currently for measuring spinal cord blood blow flow (SCBF) in animals, i.e. the hydrogen clearance, labelled microspheres, 133Xe clearance and 14C-antipyrine autoradiographic methods. All four techniques may only be used in animals, because of their invasiveness. Flow figures varied greatly with the method, the spinal level at which measurements were carried out, and the species of animal. However, results tend to suggest that SCBF is very similar to cerebral blood flow in that it is controlled by chemical, autoregulatory and metabolic factors. Approaches to measuring SCBF in man may be made using stable xenon-enhanced computed tomographic imaging (Xes-CT) in the same way as for measuring cerebral blood flow. The calculation of SCBF is based on Fick's principle transformed by Kety and Schmidt. After a reference CT section has been obtained, twelve 8 mm thick sections are carried out whilst the patient breathes a 30% xenon-70% air/oxygen mixture. This series of views enables the SCBF to be calculated in four steps. Quantitative analysis in eight human subjects gave a mean SCBF of 58.8 +/- 5.96 ml x 100 g-1 x min-1. However, this method has a low signal to noise ratio. Moreover, the qualitative analysis of the parametric views of flow demonstrate tissue heterogeneity, partly due to the patient's movements (breathing movements). However, the method is non invasive, safe, and reproducible. As it can measure very low values of blood flow, the study of ischaemic spinal lesions is made possible, although some technical and software improvements are still required.

[CT X-ray measurement of cerebral blood flow by stable xenon. Methodology and applications]. / Mesure tomodensitométrique du débit sanguin cérébral par xénon stable. Méthodologie et applications.

The measurement of cerebral blood flow by stable xenon computerized tomography is a tridimensional method that offers an excellent spatial resolution. The quantitative estimation of the cerebral blood flow is based on Fick's principle, transformed by Kety and Schmidt, using stable xenon as indicator, which is an inert and freely diffusible gas. The limitations of this method are related to the necessity for the patient to remain completely immobile during the examination, the low signal/noise ratio and the impossibility of measuring cerebral metabolism. By contrast, this method represents a real advantage in the diagnosis and prognosis of cerebral pathology: it allows the acquisition of a precise cartography of superficial and deep regional blood flows; it can reveal zones under the functional perfusion threshold thank to its capacity to measure very low blood flows; it allows the obtention of additional information in pathologies of tumoral, ischemic or degenerative origin by measuring the partition coefficient. Moreover, this technique is reliable, non invasive and reproducible. Advantages of such measurement are illustrated in revealing epileptic foci in partial seizures resistant to medical treatment, in the prognosis of cerebrovascular accidents and in the therapeutic evaluation of drugs used in animal experiments.

[Protocol for preparation, anesthesia and monitoring in therapeutic angiography]. / Protocole de préparation, d'anesthésie et de surveillance en angiographie thérapeutique.

The procedures involved in cerebral and medullary embolization produce special problems for the anesthesiologist. Some imperatives must be followed in order to minimize the high neuroradiological risks associated with these long and repetitive procedures. The first of these imperatives is sedation, which throughout the procedure should be sufficient, although not narcotic enough to prevent neurological evaluations. The use of a benzodiazepine (Midazolam) in conjunction with an analgesic (Alfentanil) that is rapidly eliminated answers this need. The prescription of vasodilatator agents depends on the location of the embolization. Calcium channel blockers should be used following embolism of the internal carotid while nitrate derivatives are recommended after embolism of the external carotid. Reduction of the risk of thrombosis is accomplished by perfusion with anti-sludge or, with exception to therapeutic procedures involving hemostasis, by perfusion with acetylsalicylic acid. Following evaluation of 105 procedures in 75 patients it is concluded that this sedation produces reliable results and allows the procedure to be performed with maximal security.

Measurement of cerebral blood flow by the stable xenon computerized tomography method.

Measurement of cerebral blood flow (CBF) by computerized tomography (CT) is a three-dimensional method with better spatial resolution than the two-dimensional methods. Its principle was first described by Drayer et al. in 1978, with stable xenon (Xes) as CBF indicator. CBF quantitation is based on Fick's principle transformed by Kety and Schmidt when the indicator is a diffusible inert gas. Xes concentrations in cerebral parenchyma and arterial blood are the initial parameters in Kety's equation; they are expressed as variations in attenuation coefficient. Examinations are performed with a Somatom DRH (Siemens) apparatus. Xes (35%) is inhaled from a closed circuit ventilation system which enables xenon to recirculate. From a console connected to the inhalator the operator can command gas preparation, start examination, acquire and transfer data. A reference ("native") section is cut at the site chosen on the topogram. Twelve sections, each 8 mm thick, are then performed while the patient inhales, during 6 minutes, the mixture: air-35% xenon + 65% oxygen. The series of images which enable the CBF parametric image to be calculated is treated in four stages: 1. Xenon concentrations in arterial blood are calculated from the Xes values measured in the air exhaled at the end of expiration. 2. All contrasted sections are visualized on the image monitor after subtraction of the background noise. 3. The CBF parametric image is calculated by Koeppe's optimization method (linear calculation of least squares), using a PDP 11/44 processor. 4. The CBF parametric image is treated to give the CBF value expressed as ml.100 g.min. The method has its limitations: it depends on the limited signal/noise ratio and on the patient's complete immobility; cerebral metabolic rates cannot be measured. But these limitations are largely outweighed by major advantages: the CT/Xes method is non-invasive, safe and reproducible. Owing to its excellent spatial resolution, it provides very accurate maps of superficial and deep regional blood flows. As it measures very low blood flows and can give partition coefficient values, it is of considerable help in the study of ischaemic and degenerative cerebral pathologies.