[Cortical spreading depolarization phenomena in patients with traumatic and ischemic brain injuries. Results of a pilot study]. / Fenómenos de despolarización cortical propagada en los pacientes con lesiones cerebrales traumáticas e isquémicas. Resultados de un estudio piloto.

OBJECTIVES: To determine the frequency and duration of cortical spreading depolarization (CSD) and CSD-like episodes in patients with traumatic brain injury (TBI) and malignant middle cerebral artery infarction (MMCAI) requiring craniotomy. DESIGN: A descriptive observational study was carried out during 19 months. SETTING: Neurocritical patients. PATIENTS: Sixteen patients were included: 9 with MMCAI and 7 with moderate or severe TBI, requiring surgical treatment. INTERVENTIONS: A 6-electrode subdural electrocorticographic (ECoG) strip was placed onto the perilesional cortex. MAIN VARIABLES OF INTEREST: An analysis was made of the time profile and the number and duration of CSD and CSD-like episodes recorded from the ECoGs. RESULTS: Of the 16 patients enrolled, 9 presented episodes of CSD or CSD-like phenomena, of highly variable frequency and duration. CONCLUSIONS: Episodes of CSD and CSD-like phenomena are frequently detected in the ischemic penumbra and/or traumatic cortical regions of patients with MMCAI who require decompressive craniectomy or of patients with contusional TBI.

The gamut of blood flow responses coupled to spreading depolarization in rat and human brain: from hyperemia to prolonged ischemia.

Cortical spreading depolarizations (SD) have been shown to occur frequently in patients with aneurysmal subarachnoid hemorrhage (SAH) and are associated with delayed ischemic brain damage. In animal models the link between SD and cell damage is the microvascular spasm coupled to the passage of SDs, resulting in spreading ischemia. Here we compared the hemodynamic changes induced by SD between human and rat cerebral cortex. Specifically, we addressed the question, whether the full spectrum of regional cerebral blood flow (rCBF) responses to SD is found in the human brain in a similar fashion to animal models. SDs were identified by slow potential changes in electrocorticographic recordings and the rCBF response profiles and magnitudes were analyzed. We found a large variability of rCBF changes concomitant to SDs in rat and in human recordings. The spectrum ranged from normal hyperemic responses to prolonged cortical spreading ischemia with intermediate forms characterized by biphasic (hypoemic-hyperemic) responses. The bandwidths of rCBF responses were comparable and the relative response magnitudes of hypo- and hyperperfusion phases did not differ significantly between rats and humans. The correspondence of the rCBF response spectrum to SD between human and animal brain underscores the importance of animal models to learn more about the mechanisms underlying the early and delayed pathological sequelae of SAH.

A fundamental role for the nitric oxide-G-kinase signaling pathway in mediating intercellular Ca(2+) waves in glia.

In this study, we highlight a role for the nitric oxide-cGMP-dependent protein kinase (NO-G-kinase) signaling pathway in glial intercellular Ca(2+) wave initiation and propagation. Addition of the NO donor molsidomine (100-500 microM) or puffing aqueous NO onto primary glial cell cultures evoked an increase in [Ca(2+)](i) in individual cells and also local intercellular Ca(2+) waves, which persisted after removal of extracellular Ca(2+). High concentrations of ryanodine (100-200 microM) and antagonists of the NO-G-kinase signaling pathway essentially abrogated the NO-induced increase in [Ca(2+)](i), indicating that NO mobilizes Ca(2+) from a ryanodine receptor-linked store, via the NO-G-kinase signaling pathway. Addition of 10 microM nicardipine to cells resulted in a slowing of the molsidomine-induced rise in [Ca(2+)](i), and inhibition of Mn(2+) quench of cytosolic fura-2 fluorescence mediated by a bolus application of 2 microM aqueous NO to cells, indicating that NO also induces Ca(2+) influx in glia. Mechanical stress of individual glial cells resulted in an increase in intracellular NO in target and neighboring cells and intercellular Ca(2+) waves, which were NO, cGMP, and G-kinase dependent, because incubating cells with nitric oxide synthase, guanylate cyclase, and G-kinase inhibitors, or NO scavengers, reduced Delta[Ca(2+)](i) and the rate of Ca(2+) wave propagation in these cultures. Results from this study suggest that NO-G-kinase signaling is coupled to Ca(2+) mobilization and influx in glial cells and that this pathway plays a fundamental role in the generation and propagation of intercellular Ca(2+) waves in glia.

Depolarisation phenomena in traumatic and ischaemic brain injury.

1. Cortical spreading depression is a non-physiological global depolarisation of neurones and astrocytes that can be initiated with varying degrees of difficulty in the normally perfused cerebral cortex in the experimental laboratory. Induction is typically with electrical stimulation, needling of the cerebral cortex, or superfusion of isotonic or more concentrated potassium chloride solution. The phenomenon propagates across the cerebral cortex at a rate of 2-5 mm per minute, and is accompanied by marked but transient increases in cerebral blood flow, in local tissue oxygen tension, and most probably in metabolic rate. 2. Peri-infarct depolarisation is also a depolarisation event affecting neurones and glia, with an electrophysiological basis similar or identical to CSD, but occurring spontaneously in the ischaemic penumbra or boundary zone in focal cerebral cortical ischaemia. Most such events arise from the edge of the ischaemic core, and propagate throughout the penumbra, at a rate similar to that of cortical spreading depression. 3. Cortical spreading depression in the normally perfused cortex does not result in histological damage whereas peri-infarct depolarisations augment neuronal damage in the penumbra, and are believed by many authors to constitute an important, or the principal, mechanism by which electrophysiological penumbra progressively deteriorates, ultimately undergoing terminal depolarisation and thus recruitment into an expanded core lesion. 4. There is some experimental evidence to suggest that under some circumstances induction of episodes of cortical spreading depression can confer protection against subsequent ischaemic insults. 5. Although cortical spreading depression and peri-infarct depolarisations have been extensively studied in the experimental in vivo models, there is now clear evidence that depolarisations also occur and propagate in the human brain in areas surrounding a focus of traumatic contusion. 6. Whether such events in the injured human brain represent cortical spreading depression or peri-infarct depolarisation is unclear. However, invasive and probably non-invasive monitoring methods are available which may serve to distinguish which event has occurred. 7. Much further work will be needed to examine the relationship of depolarisation events in the injured brain with outcome from cerebral ischaemia or head injury, to examine the factors which influence the frequency of depolarisation events, and to determine which depolarisation events in the human brain augment the injury and should be prevented.

The cortical ischaemic penumbra associated with occlusion of the middle cerebral artery in the cat: 1. Topography of changes in blood flow, potassium ion activity, and EEG.

The gyral topography of the ischaemic penumbra associated with middle cerebral artery occlusion was studied in cats; local blood flow (hydrogen clearance, 2-min initial slope analysis), pial surface potassium activity (Kp), and electroencephalogram (EEG) amplitude were recorded on the ectosylvian, suprasylvian, and marginal gyri. Penumbral conditions were defined as a reduction of EEG amplitude in the absence of a major increase in Kp. Whole hemisphere cerebral blood flow prior to occlusion was 35.6 +/- 11.4 (SD) ml 100 g-1 min-1 (n = 25), and fell significantly (p less than 0.001) to 13.0 +/- 4.7 (SD), 14.1 +/- 6.6, and 23.8 +/- 9.3 on ectosylvian, suprasylvian, and marginal gyri, respectively. Pre-occlusion Kp was 3.0 +/- 0.9 mM (n = 53); sustained, steady-state increases in excess of 11.5 mM occurred in 5 of 7 (71%) experiments on ectosylvian gyrus, in 13 of 22 (59%) experiments on suprasylvian gyrus, and in 2 of 24 experiments on marginal gyrus. Transient increases in Kp occurred at occlusion and resolved to baselines significantly higher than control in 5 (23%) experiments in suprasylvian gyrus and in 15 (63%) on marginal gyrus. In 7 experiments on the marginal gyrus (29%), no increase in Kp greater than 1 mM occurred. In contrast, EEG amplitude on this gyrus was reduced by middle cerebral artery occlusion in 25 of 26 experiments, and it is concluded that this gyrus is the principal site of ischaemic penumbra in the model; in 41% of experiments similar conditions were also present on the suprasylvian gyrus.

A double-radionuclide autoradiographic method using N-isopropyl-iodoamphetamine for sequential measurements of local cerebral blood flow.

A double-radionuclide autoradiographic method has been assessed for sequential determinations of local CBF (LCBF). It is based on two successive intravascular injections of N-isopropyl-p-iodoamphetamine (IMP) labelled with different radionuclides, whose concentrations can later be differentiated in the same tissue section using double-radionuclide autoradiography. Previous studies suggested that the distribution of IMP, up to 30 min after its administration, still represents LCBFs. Our data indicate that, provided the tracer is injected directly into the left ventricle, there is little back diffusion from normal brain to blood under physiological conditions for at least 35 min following the tracer injection and an injection of unlabelled IMP, in a dose larger than that used for blood flow determination, does not displace any labelled IMP previously taken up by the brain, nor does it displace any labelled IMP previously accumulated in the lung that would lead to secondary brain uptake. On the basis of these results, we conclude that sequential autoradiographic determinations of LCBF using IMP labelled with different radionuclides is possible. This is a promising experimental method for the simultaneous investigation of changes in LCBF in several CNS structures.

Changes in vascular and metabolic reactivity as indices of ischaemia in the penumbra.

The reactivities of cerebral cortical blood flow (hydrogen clearance) and of compensated NADH fluorescence to local cortical electrical stimulation were examined on the marginal gyrus before and after transorbital occlusion of the middle cerebral artery in cats. Prestimulus cerebral blood flow (CBF) was 38.2 +/- 12.9 (SD) ml 100 g-1 min-1 and fell to 19.8 +/- 11.1 following occlusion (p less than 0.02). Peak hydrogen clearance rate (percent increase above prestimulus clearance) was 81.6 +/- 53.6 and fell to 19.9 +/- 29.8 after middle cerebral artery occlusion (p less than 0.01). Steady-state NADH fluorescence rose from 33.5 +/- 10.7 to 40.5 +/- 17.6% full-scale deflection following MCAO (p less than 0.01). Latency from stimulus to maximal fluorescence depression in response to cortical stimulation increased from 12.2 +/- 8.2 to 22.1 +/- 11.9 s (p less than 0.01). Hyperaemic responses at anteromedial sites on the marginal gyrus significantly exceeded those at posterolateral sites. The results are interpreted as indicating early ischaemic metabolic change; however, the presence of residual vasodilator responses to stimulation suggests that flow reduction and early ischaemic change in the territory studied are not simply due to inadequate collateral input, but may also reflect deafferentation or functional suppression. The possible significance of diminished vascular reactivity in the penumbra as a cause of increased vulnerability to extracellular release of excitatory amino acids is discussed.

Digital imaging of umbelliferone clearance: a method for repeated measurements of cerebral cortical blood flow with high temporal and spatial resolution.

We have developed a procedure for digital imaging of the exposed cerebral cortex during elution of a fluorescent dye. This avoids disturbing the cortex and has provided a method for the repeated estimation of regional CBF (rCBF) with a high topographical resolution. Under varying conditions of MABP and arterial blood gases, grey-level images of the exposed cortex irradiated with ultraviolet light (340 or 370 nm) were digitised (8 bits) at 15-s intervals after the injection of 1-2 ml of saturated umbelliferone solution into the lingual or external carotid artery of anaesthetised cats and rabbits. Specifically designed software allowed (a) regions of interest (ROIs) in the exposed cortex to be defined that were automatically applied to the sequence of images in a selected clearance and (b) solution of the initial slope equation for rCBF from the decay in grey-level fluorescence by exponential regression. Separate software that solved the equation at the level of a single pixel allowed a pseudocolour map of cortical rCBF to be generated. The factors affecting the resolution of this technique have been identified and quantified. Thus consistent and reproducible results were obtained provided that the fluorescence enhancement exceeded 20 grey levels and the r2 coefficient for regression was 90% or above. Mean rCBF values of 99.5 [95% confidence interval (CI), 89.4-110] ml 100 g-1 min-1 were obtained for rabbits (N = 12; mean MABP = 75.2; mean PaCO2 = 32.9; PaO2 = 111.8; pH 7.38) and 65.1 (95% CI, 55.1-75.1) ml 100 g-1 min-1 for cats (N = 8; mean MABP = 92.8; PaCO2 = 31.5; PaO2 = 114.6, pH 7.40).(ABSTRACT TRUNCATED AT 250 WORDS)

The use of in vivo fluorescence image sequences to indicate the occurrence and propagation of transient focal depolarizations in cerebral ischemia.

A method for the detection and tracking of propagated fluorescence transients as indicators of depolarizations in focal cerebral ischemia is described, together with initial results indicating the potential of the method. The cortex of the right cerebral hemisphere was exposed for nonrecovery experiments in five cats anesthetized with chloralose and subjected to permanent middle cerebral artery (MCA) occlusion. Fluorescence with 370-nm excitation (attributed to the degree of reduction of the NAD/H couple) was imaged with an intensified charge-coupled device camera and digitized. Sequences of images representing changes in gray level from a baseline image were examined, together with the time courses of mean gray levels in specified regions of interest. Spontaneous increases in fluorescence occurred, starting most commonly at the edge of areas of core ischemia; they propagated usually throughout the periinfarct zone and resolved to varying degrees and at varying rates, depending on proximity of the locus to the MCA input. When a fluorescence transient reached the anterior cerebral artery territory, its initial polarity reversed from an increase to a decrease in fluorescence. An initial increase in fluorescence in response to the arrival of a transient may characterize cortex that will become infarcted, if pathophysiological changes in the periinfarct zone are allowed to evolve naturally.

The cortical ischaemic penumbra associated with occlusion of the middle cerebral artery in the cat: 2. Studies of histopathology, water content, and in vitro neurotransmitter uptake.

The nature of the ischaemic penumbra, as defined by suppression of electroencephalogram amplitude in the absence of increase in steady state pial surface potassium activity in excess of 13 mM, was examined in the marginal gyrus of cats subjected to middle cerebral artery occlusion. In vitro synaptosomal neurotransmitter uptake, water content (specific gravity), and histopathology at the light and electron microscopic level were studied and the results compared with those obtained at deeper, critical levels of ischaemia (less than 15 ml 100 g-1 min-1). [3H]4-Aminobutyric acid uptake was 104% of control in the marginal gyrus (NS), and 61 and 48% (p less than 0.05) in critical ischaemia. It is concluded that impairment of in vivo synaptosomal uptake is a marker of simultaneous widespread damage to neurones, rather than of a change restricted to the synaptic compartment, although the present findings cannot exclude reversible, substrate-limited impairment of uptake in vivo. Reductions in specific gravity were seen only with critical ischaemia. In 5 of 6 experiments, early or classical ischaemic neuronal cell changes and reactive glia were seen on light microscopy in restricted areas in the marginal gyrus, either in microfoci or scattered more diffusely. Ultrastructural changes were more frequent but were considered to affect only a minority of neurones. Hypotheses for selective electrophysiological suppression in penumbra are discussed.

Intercellular Ca(2+) waves in rat hippocampal slice and dissociated glial-neuron cultures mediated by nitric oxide.

Nitric oxide (NO) may participate in cell-cell communication in the brain by generating intercellular Ca(2+) waves. In hippocampal organotypic and dissociated glial-neuron (>80% glia) cultures local applications of aqueous NO induced slowly propagating intercellular Ca(2+) waves. In glial cultures, Ca(2+) waves and Mn(2+) quench of cytosolic fura-2 fluorescence mediated by NO were inhibited by nicardipine, indicating that NO induces Ca(2+) influx in glia which is dihydropyridine-sensitive. As NO treatments also depolarised the plasma membrane potential of glia, the nicardipine-sensitive Ca(2+) influx might be due to the activation of dihydropyridine-sensitive L-type Ca(2+) channels. Both nicardipine-sensitive intercellular Ca(2+) waves and propagating cell depolarisation induced by mechanical stress of individual glia were inhibited by pretreating cultures with either an NO scavenger or N(G)-methyl-L-arginine. Results demonstrate that NO can induce Ca(2+) waves in hippocampal slice cultures, and that Ca(2+) influx coupled to NO-mediated membrane depolarisation might assist in fashioning their spatio-temporal dynamics.

Synaptosomes prepared from fresh human cerebral cortex; morphology, respiration and release of transmitter amino acids.

Synaptosomes prepared from fresh human cerebral cortex were shown to be morphologically similar to those from other species. On incubation, they took up oxygen at a high and linear rate and accumulated potassium against a concentration gradient. In response to depolarization by raised extracellular K+ or addition of veratrine, they showed increased respiration, lowered tissue potassium, and enhanced release of glutamate, aspartate and GABA. The preparation may be of value for studies of neurological disorders.

Simple peroperative antimicrobial chemoprophylaxis in elective neurosurgical operations.

From August 1981 to February 1982 postoperative infections due to different strains of penicillin-resistant Staphylococcus aureus occurred in 20 of 467 patients (4.3%) undergoing elective cranial and spinal operations. These infections were not attributable to defects in procedures or the theatre environment, therefore chemoprophylaxis was instituted. In the following 8 months, when patients were given penicillin G and sulphadiazine for 5 days commencing immediately postoperatively, S. aureus infections occurred in five of 579 patients (0.9%). In a subsequent randomized uncontrolled study, infections occurred in six of 265 patients receiving penicillin (2.3%), three of 270 receiving penicillin and sulphadiazine (1.1%) and one of 45 receiving erythromycin (2.2%) immediately postoperatively for 5 days. In a further study in which 587 patients received penicillin for 5 days commencing immediately preoperatively, infections due to S. aureus occurred in six (1.1%). Infections due to gram-negative organisms were seen in five (0.4%) of 1167 patients in the two uncontrolled studies.

Extracellular potassium activity, evoked potential and tissue blood flow. Relationships during progressive ischaemia in baboon cerebral cortex.

Extracellular K+ activity (Ke), local tissue blood flow and the cortical evoked potential (EP) were measured concurrently in the cerebral cortex of baboons anaesthetised with a-chloralose. Flows were progressively reduced from normal by occlusion of the middle cerebral artery and controlled steps of exsanguination. Our data suggest that 3 stages may be identified in the disturbance of K+ homeostasis produced by progressive ischaemia. In the first stage, at flow levels similar to those sufficient to abolish the EP (12-16 ml/100 g/min), small, self-limiting increases in Ke occur, probably reflecting K+ efflux into the extracellular space (ECS) with partial impairment of K+ clearance from the ECS. The second stage occurs at distinctly lower (P less than 0.01) levels of flow (8-11 ml/100 g/min), and is characterized by a massive (30-80 mM) increase in Ke, which we attribute to an increase in ionic permeability of cell membranes with further impairment or overloading of K+ clearance mechanisms. In the third stage, at flows below about 6-8 ml/100 g/min, the data indicate an inverse relationship between flow and Ke with persisting high Ke levels, suggesting complete loss of K+ clearance. Transient increases of Ke also occur in the flow range 4-13 ml/100 g/min, the rate of recovery of Ke in their decay phase being positively corelated with flow (P less than 0.005).

Reversibility of ischaemically induced changes in extracellular potassium in primate cortex.

Following the massive increase in extracellular potassium activity that occurs in cerebral cortex when local blood flow falls below 8--11 ml/100 g/min, recovery of potassium toward normal levels might be expected when flow is restored. This study assessed the reversibility of such potassium increases, produced by middle cerebral artery occlusion in 13 baboons anaesthetised with alpha-chloralose, in relation to a wide range of ischaemic duration and density and post-occlusion flow. Potassium was measured with ion-exchanger microelectrodes and flow by hydrogen clearance. The artery was occluded for 136 +/- 63 min (mean +/- SD) and measurements were continued thereafter for 93 +/- 57 min without systemic hypertension. Upon reperfusion, partial or complete recovery (i.e., to within control confidence limits) of potassium was seen in all animals, but the rate of recovery varied widely and potassium clearance showed bi-compartmental characteristics in 7 animals. The fast component (or initial slope) rate constant was significantly correlated with post-occlusion flow and (inversely) with the duration of occlusion for which flow fell below the arbitrary threshold of 10 ml/100 g/min (the flow deficit). The slow component was unrelated to these quantities. Complete recovery was associated with a significantly higher post-occlusion flow, and smaller flow deficit, than was partial recovery. Secondary increases in potassium, associated with relatively high flow deficits and post-occlusion flows, were seen in 5 animals. These results are discussed in terms of factors that may determine potassium clearance and the possibility that elevated levels of potassium (demonstrated here to be prolonged well into the post-occlusion phase) might influence the evolution of a cortical infarct.

Fifteen-year review of the mortality of brain abscess.

Ninety consecutive cases of brain abscess admitted to this center between 1964 and 1978 have been reviewed. The overall mortality has fallen in three consecutive 5-year periods from 42 to 21 to 9.7%. A number of factors seem to be responsible for this. Early surgical intervention was associated with the reduction in mortality between the first and second 5-year periods. Recognition of the significance and extent of cerebral edema, confirmed since computed tomographic (CT) scans have been available, led to a greater use of steroids during the last 5-year period, but the number of patients thus treated was too small to permit an assessment of any effect on mortality. There is no evidence to suggest a change in the natural history of the disease, and surgical management has not altered significantly. Experience with CT scanning in this center in the diagnosis of brain abscess is limited. It is therefore not possible no assess whether any improvement in mortality may have arisen from the early and accurate diagnosis obtainable with this technique. Improvement in culture technique has been of major importance, leading to a better understanding of the bacteriology of brain abscesses. This has allowed a more rational antibiotic program to be instituted, in particular the use of agents active against obligate anaerobes.

The Maudsley Mentation test: a method for extended monitoring of mental status after aneurysmal subarachnoid hemorrhage.

A new scale for the repeated, rapid assessment of mental function in patients with subarachnoid hemorrhage is described. Its reproducibility is evaluated and early experience with its use in the intended clinical setting is reported. The test (Maudsley Mentation Test) proved to be more sensitive to fluctuations in cerebral functioning than existing measures of conscious level, and the results were reproducible among observers with different backgrounds (surgeons, nurses, and psychologists). The results suggest a relationship between performance on mentation testing and quality of outcome. The Maudsley Mentation Test is thought to offer a suitable measure with which to monitor patients during the acute phase of their illness to supplement clinical assessment and provide evidence of deterioration at an early stage. It is also potentially useful as an end point in acute protection and treatment studies.

Combined and three-dimensional rendered multimodal data for planning cranial base surgery: a prospective evaluation.

Magnetic resonance (MR), X-ray computed tomography (CT), and angiographic images best depict soft tissue, bone, and blood vessels respectively. No one on its own is sufficient in the preoperative assessment of cranial base lesions. We have developed and evaluated a computational technique for the three-dimensional (3D) combination and display of multimodality images for planning cranial base surgery. This evaluation was prospective and performed in such a way that the results could be quantified. Eight patients (three acoustic neuromas, four subfrontal and suprasellar meningiomas, and one petrous apex meningioma) underwent MR, CT, and MR angiographic investigations. These images were registered with anatomical landmarks rather than an external frame. Two techniques were used to display the resulting combined images: multiple slices in which bone from CT was overlaid on soft tissue from registered MR and pseudo-3D-rendered movie sequences showing bone from CT, lesions and optic nerves from MR, and blood vessels from MR angiography. The advantages of the combined displays compared with those of conventional methods of viewing were assessed prospectively by the operating surgeon and by an independent surgeon, and the results were compared with operative findings. The preoperative assessment showed a significant improvement (P < 0.05, sign test) in the depiction of both individual structures (lesion and bone from overlaid slices and lesion and vasculature from 3D-rendered displays) and structural relationships (tumor-bone relationships from overlaid slices and of tumor-vasculature relationships from 3D-rendered displays). The operative findings indicated that a more accurate interpretation of this information was possible from the combined images.

Cluster analysis of diffusion tensor magnetic resonance images in human head injury.

OBJECTIVE: Issues surrounding the nature of the edema associated with traumatic brain injury in humans, and its evolution in the acute phase, remain unresolved. This study aimed to characterize the topographical nature of the pathophysiological changes in human traumatic brain injury with diffusion tensor magnetic resonance imaging. METHODS: Multislice diffusion-weighted magnetic resonance imaging data were acquired from five patients undergoing elective ventilation for management of traumatic focal contusion or hematomas. The diffusion tensor and the T2-weighted intensity were then computed for every voxel in the image data set for each patient. The topographical distribution of abnormalities in the trace of the diffusion tensor and T2-weighted images were characterized by cluster analysis. RESULTS: In four patients with technically satisfactory data, a narrow band of tissue was observed in the periphery of focal lesions, which was characterized by selective reduction in the trace of the diffusion tensor, without any associated increase in the T2-weighted signal intensity. CONCLUSION: This change is interpreted as indicating either a partial redistribution of water from the extra- to intracellular compartment, or a reduction in the diffusivity of water in the intracellular or cytosolic environment. These diffusion and T2-weighted characteristics are also found in early ischemic change, hence, such regions may represent potentially salvageable tissue at risk of permanent damage. The study illustrates the advantage of using information contained within the diffusion tensor in addition to more conventional imaging sequences.

Design and evaluation of a system for microscope-assisted guided interventions (MAGI).

The problem of providing surgical navigation using image overlays on the operative scene can be split into four main tasks--calibration of the optical system; registration of preoperative images to the patient; system and patient tracking, and display using a suitable visualization scheme. To achieve a convincing result in the magnified microscope view a very high alignment accuracy is required. We have simulated an entire image overlay system to establish the most significant sources of error and improved each of the stages involved. The microscope calibration process has been automated. We have introduced bone-implanted markers for registration and incorporated a locking acrylic dental stent (LADS) for patient tracking. The LADS can also provide a less-invasive registration device with mean target error of 0.7 mm in volunteer experiments. These improvements have significantly increased the alignment accuracy of our overlays. Phantom accuracy is 0.3-0.5 mm and clinical overlay errors were 0.5-1.0 mm on the bone fiducials and 0.5-4 mm on target structures. We have improved the graphical representation of the stereo overlays. The resulting system provides three-dimensional surgical navigation for microscope-assisted guided interventions (MAGI).