Creative tensions in the research and development climate. Technical achievement of scientists and engineers was high under conditions that seemed antithetical.

As Andrews and I examined the conditions under which scientists and engineers did effective work, we observed a number of apparent paradoxes. Achievement was high under conditions that seemed inconsistent, including on the one hand sources of stability or confidence (what I have called "security") and on the other hand sources of disruption or intellectual conflict (that is, "challenge"). It appears that, if both are present, the creative tension between them can promote technical achievement.

Acute stroke with hyperdense middle cerebral artery sign benefits from IV rtPA.

OBJECTIVES: The current management of acute ischemic stroke is intravenous (IV) recombinant tissue plasminogen activator (rtPA). The presence of a hyperdense middle cerebral artery sign (HMCAS) on pre-treatment head computed tomogram (CT) is considered a poor prognostic sign. We compared the clinical outcome in IV rtPA-treated patients with and without a HMCAS. DESIGN: Retrospective analysis of prospectively collected cases treated with IV rtPA within three hours. Inclusion criteria were the presence of: i) an anterior circulation stroke; ii) a pre-treatment CT available; iii) a pre-treatment National Institutes of Health (NIH) stroke scale (NIHSS) score; and iv) a modified Rankin Score (mRS) at three months. RESULTS: One hundred and thirty patients were eligible for the analysis, 64 (49%) had a HMCAS. The HMCAS group had a trend toward a higher mean (+/-SD) pre-treatment NIHSS score compared to the non-HMCAS group (13.9+/-6 vs. 12.2+/-6; p=0.12). Accordingly, there were more patients with severe strokes (NIHSS>10) in the HMCAS group compared to the non-HMCAS one (48/64=75% vs. 35/66=53%; p=0.009). The mean (+/-SD) NIHSS score 24 hours after treatment was 10.6 (+/-8) in the HMCAS group and 8.3 (+/-7) in the non-HMCAS group (p=0.08). In a multiple logistic regression analysis, the only independent predictor of poor outcome (mRS 3-6) was pre-treatment NIHSS score (p<0.001). CONCLUSION: Patients with a HMCAS receiving IV rtPA did not fare worse at three months despite a greater proportion of patients with more severe strokes. Based on the current knowledge, IV rtPA remains a good treatment for patients with a HMCAS within three hours of symptom onset.

Identification of penumbra and infarct in acute ischemic stroke using computed tomography perfusion-derived blood flow and blood volume measurements.

BACKGROUND AND PURPOSE: We investigated whether computed tomography (CT) perfusion-derived cerebral blood flow (CBF) and cerebral blood volume (CBV) could be used to differentiate between penumbra and infarcted gray matter in a limited, exploratory sample of acute stroke patients. METHODS: Thirty patients underwent a noncontrast CT (NCCT), CT angiography (CTA), and CT perfusion (CTP) scan within 7 hours of stroke onset, NCCT and CTA at 24 hours, and NCCT at 5 to 7 days. Twenty-five patients met the criteria for inclusion and were subsequently divided into 2 groups: those with recanalization at 24 hours (n=16) and those without (n=9). Penumbra was operationally defined as tissue with an admission CBF <25 mL x 100 g(-1) x min(-1) that was not infarcted on the 5- to 7-day NCCT. Logistic regression was applied to differentiate between infarct and penumbra data points. RESULTS: For recanalized patients, CBF was significantly lower (P<0.05) for infarct (13.3+/-3.75 mL x 100 g(-1) x min(-1)) than penumbra (25.0+/-3.82 mL x 100 g(-1) x min(-1)). CBV in the penumbra (2.15+/-0.43 mL x 100 g(-1)) was significantly higher than contralateral (1.78+/-0.30 mL x 100 g(-1)) and infarcted tissue (1.12+/-0.37 mL x 100 g(-1)). Logistic regression using an interaction term (CBFxCBV) resulted in sensitivity, specificity, and accuracy of 97.0%, 97.2%, and 97.1%, respectively. The interaction term resulted in a significantly better (P<0.05) fit than CBF or CBV alone, suggesting that the CBV threshold for infarction varies with CBF. For patients without recanalization, CBF and CBV for infarcted regions were 15.1+/-5.67 mL x 100 g(-1) x min(-1) and 1.17+/-0.41 mL x 100 g(-1), respectively. CONCLUSIONS: We have shown in a limited sample of patients that CBF and CBV obtained from CTP can be sensitive and specific for infarction and should be investigated further in a prospective trial to assess their utility for differentiating between infarct and penumbra.

Frontal, temporal, and striatal proton relaxation times in schizophrenic patients and normal comparison subjects.

Spin-lattice (T1) and spin-spin (T2) magnetic resonance relaxation times were examined in frontal, temporal, and striatal regions of 24 patients with schizophrenia and 10 normal comparison subjects. The schizophrenic patients had more prolonged T2 values than did the comparison subjects, particularly in the left temporal cortex and white matter, suggesting tissue pathology.

Interobserver variation in computed tomography of the brain.

As part of the University of Western Ontario Dementia Study, the computed tomographic brain scans of 16 patients were reviewed by three neuroradiologists. The size of the ventricles and sulci were rated using a six-point scale. Infarction and white matter changes were assessed in accordance with specified criteria. The interobserver correlations in this small series were statistically significant in 17 of 20 items, and good or acceptable for infarction, leuko-araiosis, and ventricular size. It is suggested that the use of rigid criteria for the definition of abnormality helps to promote interobserver agreement.

The impact of magnetic resonance imaging on the management of acute ischemic stroke.

Despite rapid advances in imaging technology, the etiology of stroke remains unestablished in 40% of patients. MRI improves localization in acute stroke. However, it is not known whether "accurate localization" results in better management. We reviewed the hospital records of all patients admitted with a diagnosis of acute ischemic stroke and who had had cranial CTs and MRI within 10 days of admission. Between January 1987 and June 1990, 116 patients (69 men, 47 women; mean age, 66 years) were identified. Compared with CT localization, infarcts were better localized in nine of 39 patients with cerebral cortical lesions, in 20 of 22 patients with brainstem and cerebellar lesions, and in three of three patients with isolated cerebellar lesions. In 22 patients (18.9%), MRI showed multiple infarcts in two or more vascular territories, suggesting embolic disease and leading to anticoagulation. MRI also showed arterial occlusions in 11 patients (9.5%). Based on the information obtained with MRI, the clinical diagnosis was changed in 19 patients (16.3%), resulting in changes in the management of most of those patients. Thus, we confirm earlier reports that MRI improves localization after acute cerebral infarction and show that such information alters patient management.

Central pontine myelinolysis and cyclosporine neurotoxicity following liver transplantation.

In a recent series of 44 liver transplants we identified both extrapontine myelinolysis (EPM) - characteristic of cyclosporine neurotoxicity - and central pontine myelinolysis (CPM) in 5 recipients posttransplant. An additional 2 recipients had EPM only posttransplant. MRIs performed in 4 asymptomatic recipients were normal. Large perioperative shifts in serum sodium, hypomagnesemia, and high cyclosporine levels may play a role in the development of these lesions, although the evidence from this study is inconclusive. In addition to supportive care, dilantin was started in patients who had seizures; aggressive magnesium replacement was initiated for hypomagnesemia, and cyclosporine levels were reduced in all patients. All patients demonstrated a slow steady recovery and all but 2 are at home at the time of writing. CPM may be more prevalent than previously appreciated following liver transplantation, although its prognosis may not be as dismal.

Iohexol cerebral angiography. Multicenter clinical trial.

Ionic contrast media currently used in cerebral angiography frequently cause discomfort due to hyperosmolality. This double-blind, multicenter trial compared two ionic media, meglumine iothalamate and meglumine-Na diatrizoate, with the new nonionic agent, iohexol, in 277 patients undergoing cerebral angiography. Vital signs, cardiovascular changes, and neurologic status were evaluated before, during, and after injection. Patients were observed for adverse reactions for up to 24 hours following studies. Patient discomfort and image quality were evaluated. Visualization was good or excellent with all media studied. No significant physiological differences were observed between the ionic and iohexol groups, but fewer iohexol patients experienced large increases (greater than 20 mmHg) in systolic blood pressure. Iohexol patients experienced significantly less discomfort; ionic patients reported severe discomfort 21/2 times more often. This finding was attributed to iohexol's low osmolality. Iohexol may be indicated particularly for use in selective angiograms where discomfort is a factor and for patients suspected of having blood-brain barrier disruption.

Cavernous aneurysm rupture with balloon occlusion of a direct carotid cavernous fistula: postmortem examination.

We present a unique case of a patient with a symptomatic carotid cavernous fistula treated successfully with balloon embolization. Her subsequent death from other disease processes allowed direct visualization of the balloon occlusion in situ at postmortem examination.

Clinical trial of Iohexol vs. Conray 60 for cerebral angiography.

Iohexol, a new nonionic contrast agent, and Conray 60 were compared in a double-blind clinical trial of 60 patients for safety, imaging effectiveness, and patient discomfort in cerebral angiography. There was no significant difference between the two agents in physiologic changes, film quality, or incidence of adverse effects in the 60 patients. One patient in the iohexol group suffered a cardiac arrest, which was clinically due to septic shock and was probably the result of inadvertent contamination of the iohexol used for test injections in this case. Bacterial growth can be supported in iohexol under certain circumstances, due to the lack of preservatives in this contrast material. The patients in the iohexol group experienced significantly less discomfort than the Conray 60 group. Iohexol is a safe, effective contrast agent when handled properly and causes less discomfort to patients than Conray 60.

Angiographic follow-up of large cerebral AVMs incompletely embolized with isobutyl-2-cyanoacrylate.

This study evaluated the long-term angiographic results in large cerebral arteriovenous malformations (AVMs) partially embolized with isobutyl-2-cyanoacrylate. Preembolization, immediate postembolization, and long-term follow-up angiograms were performed in 30 large, partially embolized brain AVMs. Particular attention was paid to the relative size of the residual AVM nidus and the embolized arterial feeders, to recruitment of new feeders, to the size of residual draining veins, and to the speed of arteriovenous shunt. Nine cases with less than 50% AVM nidus obliteration showed no significant morphologic changes. In 18 cases with 50-75% obliteration of the AVM nidus, 11 (61.1%) showed no significant changes, six (33.3%) showed enlargement of the AVM nidus, and one (5.5%) evolved to complete angiographic obliteration. In three cases with 75-99% AVM nidus obliteration, one remained unchanged, one showed an increase in the size of the AVM nidus, and one evolved to complete obliteration. Evaluation by plain film, CT, and cerebral angiography of the isobutyl-2-cyanoacrylate deposits showed that when the polymer was positioned predominantly in arterial feeders there was invariably reconstitution of the AVM nidus through leptomeningeal, deep medullary, and/or dural collaterals. This phenomenon did not occur when the isobutyl-2-cyanoacrylate was deposited mainly in the AVM nidus.

A comparison of iopamidol and iohexol in cerebral angiography.

Iopamidol and iohexol, the new nonionic low-osmolality contrast agents, have both been shown to be safe, effective, and better tolerated than conventional ionic agents for cerebral angiography. In this randomized, double-blind study involving 40 patients, these two agents were compared for adverse effects, radiographic quality, and patient tolerance. No significant differences were observed in 220 injections. Because we found iopamidol and iohexol to be equally safe and effective for cerebral angiography, the choice of which contrast agent to use should be based on other considerations.

Thromboembolic events associated with the treatment of cerebral aneurysms with Guglielmi detachable coils.

BACKGROUND AND PURPOSE: The purpose of this study was to document the prevalence, radiologic appearance, and treatment of thromboembolic events related to GDC embolization of cerebral aneurysms. METHODS: The clinical and radiologic records of all patients undergoing GDC treatment of intracranial aneurysms at our institution were reviewed. All cases in which unexpected complications occurred were selected. Those complications related to presumed thromboembolic events were analyzed. RESULTS: Of 59 patients (60 aneurysms) treated with GDCs, 17 (28%) experienced thromboembolic events. Seven patients had transient ischemic attacks and 10 had strokes. In 10 patients, the deficits occurred during or immediately after the procedure; in the rest, the complications were delayed. In six patients, all radiologic investigations were negative for infarction and in seven patients, CT scans showed new ischemic lesions. In four patients, MR imaging alone showed infarcts, and in four of nine patients who underwent subsequent angiography, acute ischemic findings were demonstrated. Eight patients were treated with volume expansion, eight with full heparinization, and one patient underwent intraarterial thrombolysis. Clinical outcome was excellent or good in 14 of 17 patients, with only three patients (5%) incurring permanent neurologic deficits. CONCLUSION: Thromboembolic events related to GDC treatment may be more common than has been reported in the literature. In our experience, this rate was 28%, with persisting deficits in 5%. These events can occur after uncomplicated procedures and may be unaccompanied by radiologic findings. Clinical outcome is usually favorable.

Preembolization superselective angiography: role in the treatment of brain arteriovenous malformations with isobutyl-2 cyanoacrylate.

Transfemoral and intraoperative embolization of arteriovenous malformations (AVMs) of the brain with isobutyl-2 cyanoacrylate may achieve complete and permanent occlusion of the AVMs. The preembolization superselective angiogram is an important source of information to decrease potential technical or clinical complications while seeking that goal. The information obtained from the angiogram of each individual feeder may be classified as anatomical, dynamic, and functional. This angiogram is performed either through a calibrated-leak balloon glued to a Silastic tubing, which is capable of negotiating cortical arterial curves, or through a short catheter directly placed into a feeder at surgery. In 64 patients, 175 preembolization superselective angiograms were obtained. Of those, 105 were obtained using the transfemoral technique, and 70 were obtained by direct catheterization after a craniotomy. Complications occurred in eight patients with only one permanent injury. Transient neurologic deficit occurred in five patients. One patient developed a permanent left monoplegia and one patient a subarachnoid hemorrhage without permanent neurologic deficit. In one patient, a delayed intracerebral hemorrhage produced a right hemiplegia and aphasia. The patient fully recovered in 6 months.

Symptomatic pulmonary complications from liquid acrylate embolization of brain arteriovenous malformations.

PURPOSE: To describe symptomatic pulmonary emboli from brain arteriovenous malformation embolization with liquid acrylates and to analyze the reasons for these complications and describe preventive techniques. METHODS: The clinical records of 182 patients embolized with acrylate glue since 1978 for treatment of brain AVMs were searched for evidence of symptomatic pulmonary complications. Originally iso-butyl-2-cyanoacrylate and more recently n-butyl-2-cyanoacrylate were used in all patients. Arteriovenous malformation morphology, amounts and techniques of glue injection, and clinical and radiologic investigations in the symptomatic patients were recorded. RESULTS: Three patients had pulmonary symptoms within 48 hours of glue injection. One patient with a left frontal arteriovenous malformation had embolization with an isobutyl-2-cyanoacrylate/pantopaque/acetic acid mixture; severe pleuritic chest pain developed 2 days later. One patient with a left temporal and one with a left cerebellar arteriovenous malformation had embolization with n-butyl-2-cyanoacrylate/lipiodol mixtures; a cough, pleuritic chest pain, and bloody sputum developed in both within 24 hours. Two patients experienced a significant drop in PO2. No flow-arrest techniques were used for any of the injections in these three patients. All patients demonstrated significant changes on chest x-ray and CT chest examinations. All were treated conservatively and recovered spontaneously. CONCLUSIONS: Symptomatic pulmonary complications can occur after acrylate glue injection, particularly when delivery systems without flow arrest are used in high-flow vascular brain lesions. Techniques using acetic acid to delay polymerization time and "sandwich" techniques in which glue is pushed with dextrose are also more susceptible to this complication.

Preoperative embolization of brain AVMs with isobutyl-2 cyanoacrylate.

The role of embolization in the management of brain arteriovenous malformations remains controversial. The benefits of embolization alone are not clear and surgical removal may be technically difficult or impossible in many cases. In an attempt to facilitate surgical removal, we performed preoperative embolization in 15 cases using a mixture of isobutyl-2 cyanoacrylate and glacial acetic acid. In one case, a mixture of polyvinyl alcohol particles, microfibrillar collagen, and 30% ethanol was used. In 10 of these cases the surgeon felt that the embolization significantly aided the operative removal by decreasing blood loss, reducing the size of draining veins, and removing portions of the nidus itself. In no patient did the embolization result in an unanticipated significant neurologic deficit. The major role for embolization in the management of brain arteriovenous malformations may be as an aid to surgical removal.

Duplex and color Doppler flow sonography of occlusion and near occlusion of the carotid artery.

PURPOSE: To determine whether color Doppler flow imaging with the use of slow-flow sensitivity improves sensitivity and specificity in the differentiation of occlusion and near occlusion of the internal carotid artery. METHODS: Color Doppler and duplex sonography were performed in symptomatic patients who had angiographically confirmed occlusion and/or near occlusion of the internal carotid artery. The study consisted of two phases: in the first, we assessed the usefulness of color Doppler flow imaging by retrospectively reviewing the records of 35 patients with 36 angiographically confirmed occlusions or near occlusions of the internal carotid artery who were examined with color Doppler flow imaging at our institution during a period of 4 years; in the second phase, we incorporated color Doppler sonography into the routine scanning protocols of 39 patients with 41 occluded or nearly occluded internal carotid arteries seen over a period of 2 1/2 years. RESULTS: Overall, color Doppler imaging correctly showed all 34 of the near occlusions (sensitivity, 100%) and 36 of the 43 occlusions (specificity, 84%). Seven patients with angiographically confirmed occlusion had sonographic findings that suggested near occlusion. In the first phase, eight near occlusions were misinterpreted as occlusions with conventional duplex sonography, but were correctly shown with color Doppler flow imaging. In the second phase, sensitivity increased from 50% to 100% (18 or 18) because of better detection of the nearly occluded lumen. This was at the expense of a decrease in specificity (from 100% to 78%). owing to identification of apparent flow in the internal carotid artery on color Doppler flow images in five of 23 occlusions. CONCLUSION: Because of its ability to depict slow flow, color Doppler imaging with slow-flow sensitivity is superior to conventional duplex sonography for the noninvasive discrimination of occlusion from near occlusion of the internal carotid artery.

MR imaging after surgery for vertebrobasilar aneurysm.

We examined the safety and utility of high-field MR in patients who had surgery for cerebral aneurysms of the vertebrobasilar system. Eighteen posterior (and three coincidental anterior) circulation aneurysms were treated. Twenty-one MR scans were obtained at a mean postoperative interval of 7.2 days. The mean size of the preoperative vertebrobasilar aneurysm was 2.2 cm; six were giant (greater than 2.5 cm) and eight were large (greater than 1.5, less than or equal to 2.5 cm). In 17 patients, Sugita nonmagnetic clips were used. In one other, a Drake tourniquet was used. No ill effects occurred from scanning with a high-field imaging unit at 1.5 T. The MR clip artifact was much less obtrusive than that on CT. In 11 cases, the aneurysm could be partially imaged postoperatively, mainly in very large aneurysms or in those treated by clipping the parent vessel. Of these, two revealed residual lumina on MR and nine looked completely thrombosed. Postoperative angiography showed that in four of the thrombosed-appearing aneurysms a residual lumen with a mean diameter of 1.0 cm had been missed. In the patient imaged after application of a Drake tourniquet, no artifact was seen, and a good assessment of progressive partial thrombosis was obtained. Evolution of the signal intensity of new aneurysm thrombus, in those minimally or not obscured by artifact, coincides with patterns previously described for hemoglobin in intracerebral hematomas. The earliest hyperintensity could be seen in either the periphery or the center of the new thrombus. All 15 patients examined with new postoperative deficits showed appropriate lesions, mainly small brainstem ischemic foci. Postoperative CT (performed in all but four of these patients) missed over 80% of these lesions, mainly owing to artifact from clip or bone. We conclude that MR is better than CT in the postoperative assessment of aneurysm patients, particularly in demonstrating small zones of ischemia. High-field MR scanning is safe if nonmagnetic surgical clips are used. MR is not accurate in assessing residual lumina.