Magnetic microparticles for endovascular aneurysm treatment: in vitro and in vivo experimental results.

OBJECTIVE: Endovascular treatment of intracranial aneurysms employing endosaccular coiling can be associated with aneurysm perforation, coil herniation or incomplete obliteration fueling the interest to investigate novel endovascular techniques. We aimed to test a novel embolization material in experimental aneurysms in vitro and in vivo whereby intra-arterially administered magnetic microparticles (MMPs) are navigated into the lumen of vascular aneurysms with assistance from an external magnetic field. METHODS: MMPs are core-shell particles suspended in saline that have a shell made of a polymeric material and a core made of magnetite (Fe3O4). They have a diameter of 1.4 µm. During MMP administration via a microcatheter, a magnetic field was applied externally to direct the particles with the use of a solid-state neodymium magnet. Experiments were performed in a perfused silicone vessel and aneurysm model to evaluate application techniques and fluid dynamics and in the elastase aneurysm model in rabbits to evaluate in vivo compatibility, including multiorgan histological examinations and long-term stability of aneurysm embolization. RESULTS: It was possible to steer and hold the MMPs within the aneurismal cavity where they occluded the lumen progressively. After removal of the external magnetic field, the results remained stable in vivo for the remainder of the observational period (30 minutes); after a 12-week observational period, recanalization of the aneurysm occurred. CONCLUSION: MMPs can be magnetically directed into aneurysms, allowing short-term obliteration. Although the method has yet to show reliable long-term stability, these experiments provide proof of concept, encouraging further investigation of intravascular magnetic compounds.

Addition of intravenous N-methyl-D-aspartate receptor antagonists to local fibrinolytic therapy for the optimal treatment of experimental intracerebral hemorrhages.

OBJECT: Fibrinolytic therapy with recombinant tissue plasminogen activator (rtPA) is considered a treatment option in patients with deep-seated intracerebral hemorrhage (ICH). Nevertheless, the results of animal experiments have shown that tPA exerts pleiotropic actions in the brain, including regulation of vasoactivity, amplification of calcium conductance by cleavage of the N-methyl-D-aspartate (NMDA) receptor subunit, and activation of metalloproteinases, which increase excitotoxicity, damage the blood-brain barrier, and worsen edema. The authors investigated whether the noncompetitive NMDA receptor antagonist MK801 can be used as an adjuvant therapy in combination with rtPA to attenuate the unfavorable delayed edema formation and inflammation observed following rtPA therapy in an experimental porcine model of ICH. METHODS: Twenty pigs were used in this study; MK801 (0.3 mg/kg) was administered to each pig intravenously immediately after hematoma induction and on the 1st and 3rd day after hematoma induction. Ten of the 20 pigs were randomly assigned to fibrinolytic therapy with rtPA (MK801-tPA group), whereas in the remaining 10 control animals (MK801 group) the hematomas were allowed to follow their natural courses of resorption. The extent of edema formation was evaluated using magnetic resonance (MR) imaging volumetry on Days 0, 4, and 10 after hematoma induction and was compared with histopathological changes found at necropsy. The mean edema volumes in these two groups were also compared with that in the group of nine pigs examined in a preceding experimental series, in which the animals' hematomas were only treated with rtPA (tPA group). In the 10 animals in the MK801-tPA group, the mean perihematoma edema volume on MR images had not significantly increased by Day 4 (p < 0.08) or Day 10 (p < 0.35) after hematoma induction. In the 10 animals in the MK801 group, the increase in mean perifocal edema size was significant after 4 days (p < 0.001) and nonsignificant after 10 days (p < 0.09). In the nine animals in the tPA group, the mean edema volume significantly increased by Days 4 (p < 0.002) and 10 (p < 0.03). CONCLUSIONS: As suggested by the reduction in delayed edema volume and the inflammatory response, MK801 modifies the neurotoxic properties of rtPA but not those of blood degradation products. Possibly, fibrinolytic therapy of ICH is more beneficial if combined with agents such as MK801.

Clinical hypnosis modulates functional magnetic resonance imaging signal intensities and pain perception in a thermal stimulation paradigm.

OBJECTIVE: This study was designed to describe regional changes in blood oxygenation level dependent signals in functional magnetic resonance images (fMRI) elicited by thermal pain in hypnotized subjects. These signals approximately identify the neural correlates of the applied stimulation to identify neuroanatomic structures involved in the putative effects of clinical hypnosis on pain perception. METHODS: After determination of the heat pain threshold of 12 healthy volunteers, fMRI scans were performed at 1.5 Tesla by using echoplanar imaging technique during repeated painful heat stimuli. Activation of brain regions in response to thermal pain during hypnosis (using a fixation and command technique of hypnosis) was compared with responses without hypnosis. RESULTS: With hypnosis, less activation in the primary sensory cortex, the middle cingulate gyrus, precuneus, and the visual cortex was found. An increased activation was seen in the anterior basal ganglia and the left anterior cingulate cortex. There was no difference in activation within the right anterior cingulate gyrus in our fMRI studies. No activation was seen within the brainstem and thalamus under either condition. CONCLUSION: Our observations indicate that clinical hypnosis may prevent nociceptive inputs from reaching the higher cortical structures responsible for pain perception. Whether the effects of hypnosis can be explained by increased activation of the left anterior cingulate cortex and the basal ganglia as part of a possible inhibitory pathway on pain perception remains speculative given the limitations of our study design.