Tissue at risk of infarction rescued by early reperfusion: a positron emission tomography study in systemic recombinant tissue plasminogen activator thrombolysis of acute stroke.

Thrombolytic therapy of acute ischemic stroke can be successful only as long as there is penumbral tissue perfused at rates between the thresholds of normal function and irreversible structural damage, respectively. To determine the proportion of tissue at risk of infarction, cerebral perfusion was studied in 12 patients with acute ischemic stroke who underwent treatment with systemic recombinant tissue plasminogen activator (0.9 mg/kg body weight according to National Institute of Neurological Disorders and Stroke protocol) within 3 hours of onset of symptoms, using [15O]-H2O positron emission tomography (PET) before or during, and repeatedly after thrombolysis. The size of the regions of critically hypoperfused gray matter were identified on the initial PET scans, and changes of perfusion in those areas were related to the clinical course (followed by the National Institutes of Health stroke scale) and to the volume of infarcted gray matter demarcated on magnetic resonance imaging 3 weeks after the stroke. Whereas the initial clinical score was unrelated to the size of the ischemic area, after 3 weeks there was a strong correlation between clinical deficit and volume size of infarcted gray matter (Spearman's rho, 0.96; P < 0.001). All patients with a severely hypoperfused (< 12 mL/100 g/min) gray matter region measuring less than 15 mL on first PET showed full morphologic and clinical recovery (n = 5), whereas those with ischemic areas larger than 20 mL developed infarction and experienced persistent neurologic deficits of varying degree. Infarct sizes, however, were smaller than expected from previous correlative PET and morphologic studies of patients with acute stroke: only 22.7% of the gray matter initially perfused at rates below the conventional threshold of critical ischemia became necrotic. Actually, the percentage of initially ischemic voxels that became reperfused at almost normal levels clearly predicted the degree of clinical improvement achieved within 3 weeks. These sequential blood flow PET studies demonstrate that critically hypoperfused tissue can be preserved by early reperfusion, perhaps related to thrombolytic therapy. The results correspond with experimental findings demonstrating the prevention of large infarcts by early reperfusion to misery perfused but viable tissue.

Intracranial EEG versus flumazenil and glucose PET in children with extratemporal lobe epilepsy.

OBJECTIVE: To compare abnormalities determined in 2-deoxy-2-[18F]fluoro-D-glucose (FDG) and [11C]flumazenil (FMZ) PET images with intracranial EEG data in patients with extratemporal lobe epilepsy. BACKGROUND: Although PET studies with FDG and FMZ are being used clinically to localize epileptogenic regions in patients with refractory epilepsy, the electrophysiologic significance of the identified PET abnormalities remains poorly understood. METHODS: We studied 10 patients, mostly children (4 boys, 6 girls, aged 2 to 19 years; mean age, 11 years), who underwent FDG and FMZ PET scans, intracranial EEG monitoring, and cortical resection for intractable epilepsy. EEG electrode positions relative to the brain surface were determined from MRI image volumes. Cortical areas of abnormal glucose metabolism or FMZ binding were determined objectively based on asymmetry measures derived from homotopic cortical areas at three asymmetry thresholds. PET data were then coregistered with the MRI and overlaid on the MRI surface. A receiver operating characteristics (ROC) analysis was performed to determine the specificity and sensitivity of PET-defined abnormalities against the gold standard of intracranial EEG data. RESULTS: FMZ PET detected at least part of the seizure onset zone in all subjects, whereas FDG PET failed to detect the seizure onset region in two of 10 patients. The area under the ROC curves was higher for FMZ than FDG PET for both seizure onset (p = 0.01) and frequent interictal spiking (p = 0.04). Both FMZ and FDG PET showed poor performance for detection of rapid seizure spread (area under the ROC curve not significantly different from 0.5). CONCLUSIONS: [11C]flumazenil (FMZ) PET is significantly more sensitive than 2-deoxy-2-[18F]fluoro-D-glucose (FDG) PET for the detection of cortical regions of seizure onset and frequent spiking in patients with extratemporal lobe epilepsy, whereas both FDG and FMZ PET show low sensitivity in the detection of cortical areas of rapid seizure spread. The application of PET, in particular FMZ PET, in guiding subdural electrode placement in refractory extratemporal lobe epilepsy will enhance coverage of the epileptogenic zone.

Preoperative activation and intraoperative stimulation of language-related areas in patients with glioma.

OBJECTIVE: Evaluation of the accuracy of preoperative localization of language-related cortex by magnetic resonance imaging-guided positron emission tomography. METHODS: Patients with gliomas in the left dominant hemisphere were examined preoperatively with magnetic resonance imaging-guided positron emission tomography and intraoperatively by electrical stimulation of cortex. RESULTS: A verb generation task yielded more intense and better lateralized local increases of cerebral blood flow in the positron emission tomographic examination than did a naming task. Significant correspondence of preoperative and intraoperative findings was observed for the verb generation task. Cortical sites with aphasic disturbance during electrical stimulation had a significantly higher cerebral blood flow increase during preoperative activation than did sites without intraoperative language impairment. Areas with cerebral blood flow increases above an optimum threshold had 73% sensitivity and 81% specificity to predict aphasic disturbance during intraoperative stimulation. CONCLUSION: The data suggest that with further technical improvements, imaging of language function may become a preoperative diagnostic tool for patients with tumors close to language-related brain structures.

Clinical applications of registration and fusion of multimodality brain images from PET, SPECT, CT, and MRI.

Several image registration and fusion techniques have been discussed in the context of applying them to patient studies obtained during clinical workup. Mainly retrospective techniques, either automated or interactive, seem to be flexible enough to be adapted to clinical situations. Examples are provided to express the usefulness of multi-modality, multi-tracer brain studies.

Short-term memory deficit after focal parietal damage.

The neuropsychological symptomatology is reported for a 44-year-old patient of normal intelligence, EE, after removal of a circumscribed left hemispheric tumor the major part of which was located in the angular gyrus and in the subcortical white matter. EE had a distinct and persistent short-term memory impairment together with an equally severe impairment in transcoding numbers. On the other hand, his performance was flawless in calculation tasks and in all other tests involving number processing. Impairments in language tests could be attributed to his short-term memory deficit, which furthermore was characterized by a strong primacy effect in the absence of a recency effect. His graphomotoric output was temporarily inhibited. The patient, with a strong left-sided dominance, manifested a bi-hemispherical activation of the Broca and Wernicke regions in a positron-emission-tomographic investigation when required to produce verbs which he was to derive from nouns. The findings in EE suggest that unilateral and restricted lateral parietal damage can result in a profound short-term memory deficit together with a transcoding deficit for stimuli extending over only a few digits or syllables in the absence of any symptoms of the Gerstmann syndrome.

Individual functional anatomy of verb generation.

Examination of the individual functional anatomy of language is of particular interest in clinical neurology to explain the variability of aphasic symptoms after focal lesions and to avoid damage of language-related brain areas by surgery. For a silent verb generation task, we examined whether activation PET with 3D data acquisition, multiple replication of conditions, and coregistration with MRI provides results that are consistent and reproducible enough to be useful clinically. Visual analysis was performed on PET-MRI fusion images, including renderings of the brain surface. Quantitative analysis was based on volumes of interest. In seven right-handed normals, activation of the triangular part of the left inferior frontal cortex [Brodman area (BA) 45] was the most significant finding that was present in each subject. Two subjects showed minor anatomical variants of the ascending or horizontal ramus of the sylvian fissure that were associated with the least activation of BA 45. In the left hemisphere the other frontal gyri, the superior temporal and posterior part of the middle temporal gyrus, and the paracingulate gyrus were also significantly activated. There was significant bilateral cerebellar activation, but it was significantly more intense on the right than on the left side. The consistency and high interindividual reproducibility of these findings suggest that this technique may be useful for clinical assessment of language-related areas.

Localization of language-related cortex with 15O-labeled water PET in patients with gliomas.

Measurement of relative cerebral blood flow (CBF) with 15O-labeled water PET has been widely used for brain mapping experiments on language functions in normal volunteers and patients with epilepsy. We focused on the question of whether PET during speech activation is an appropriate method for noninvasive determination of language-related cortex in patients with brain tumors. Furthermore, the suitability of the method for determination of hemispheric language dominance was examined and compared to the results of the Edinburgh Handedness Inventory. Ten right-handed and six left-handed patients with gliomas were examined prior to surgery while repeatedly performing word repetition and verb generation tasks. A set of volumes of interest (VOIs) was drawn on coregistered MRI in order to account for anatomic variability as well as anatomical alterations due to tumor mass effect. Repetition of nouns did not produce significant hemispheric differences. During stimulation by verb generation, reliable lateralized activations of Broca's area and supplementary motor area were detected in all right-handed patients. Of the left-handed patients, two showed clear right lateralization, two activated Broca's area bilaterally, and two had a pattern similar to that of right-handers. Patients with bilateral activations showed the strongest tendency toward bihandedness according to the handedness inventory. Lateralization of supplementary motor area in left-handers corresponded to lateralized activity in Broca's area. Tumors in the vicinity of language-related regions did not alter activation responses. In conclusion, measurement of CBF changes during verb generation permits identification of language-related areas in patients with gliomas with strong lateralization related to hemispheric dominance. These findings may be of particular clinical interest for left-handed patients.