Quantitative CT densitometry for predicting intracerebral hemorrhage growth.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage growth independently predicts disability and death. We hypothesized that noncontrast quantitative CT densitometry reflects active bleeding and improves predictive models of growth. MATERIALS AND METHODS: We analyzed 81 of the 96 available baseline CT scans obtained <3 hours post-ICH from the placebo arm of the phase IIb trial of recombinant factor VIIa. Fifteen scans could not be analyzed for technical reasons, but baseline characteristics were not statistically significantly different. Hounsfield unit histograms for each ICH were generated. Analyzed qCTD parameters included the following: mean, SD, coefficient of variation, skewness (distribution asymmetry), and kurtosis ("peakedness" versus "flatness"). These densitometry parameters were examined in statistical models accounting for baseline volume and time-to-scan. RESULTS: The coefficient of variation of the ICH attenuation was the most significant individual predictor of hematoma growth (adjusted R(2) = 0.107, P = .002), superior to BV (adjusted R(2) = 0.08, P = .006) or TTS (adjusted R(2) = 0.03, P = .05). The most significant combined model incorporated coefficient of variation, BV, and TTS (adjusted R(2) = 0.202, P = .009 for coefficient of variation) compared with BV and TTS alone (adjusted R(2) = 0.115, P < .05). qCTD increased the number of growth predictions within ±1 mL of actual 24-hour growth by up to 47%. CONCLUSIONS: Heterogeneous ICH attenuation on hyperacute (<3 hours) CT imaging is predictive of subsequent hematoma expansion and may reflect an active bleeding process. Further studies are required to determine whether qCTD can be incorporated into standard imaging protocols for predicting ICH growth.

Radiologic estimation of hematoma volume in intracerebral hemorrhage trial by CT scan.

BACKGROUND AND PURPOSE: Therapeutic intervention during the early stages of an intracerebral hemorrhage (ICH) might have value in improving clinical outcomes. During the 73-site International Recombinant Activated Factor VII Intracerebral Hemorrhage Trial, CT techniques were used to monitor the change in hematoma volume in response to treatment. The use of CT imaging technology served 3 functions: to provide accurate measurements of the change in hematoma volume, intraventricular volume (IVH), and edema volume; to evaluate the use of CT scans as a predictor of patient outcomes; and to demonstrate that hematoma volume can serve as a surrogate marker for ICH clinical progression. METHODS: The multicenter clinical trial received institutional review board approval and obtained informed consent from the patient or a legally acceptable representative (waived in a few cases of incapacity, according to local and national regulations). CT scans were used to quantify volumes of hemorrhage and to monitor evolution over a 72-hour period in patients with ICH treated with placebo or 40, 80, or 160 microg/kg of recombinant activated factor VII (rFVIIa). CT image data were transmitted digitally to an imaging laboratory and analyzed by 2 readers masked to patient and treatment data, by using Analyze software, a fully integrated toolkit for interactive display, processing, and measurement of biomedical image data. The use of this software enabled the evaluation of intraclass variability of CT scan interpretations. RESULTS: Interpretations of ICH and IVH volumes of CT scans in patients treated in this study showed minimal intraclass variability. Variability was greatest for interpretations of edema volume. CONCLUSION: These CT assessments of lesions could have value in future early hemostatic interventions in ICH patients.

Revision of deep brain stimulator for tremor. Technical note.

The treatment of essential tremor with thalamic deep brain stimulation (DBS) is considered to be more effective and to cause less morbidity than treatment with thalamotomy. Nonetheless, implantation of an indwelling electrode, connectors, and a generator is associated with specific types of morbidity. The authors describe three patients who required revision of their DBS systems due to lead breakage. The connector between the DBS electrode and the extension wire, which connects to the subclavicular pulse generator, was originally placed subcutaneously in the cervical region to decrease the risk of erosion through the scalp and to improve cosmesis. Three patients presented with fractured DBS electrodes that were located in the cervical region near the connector, necessitating reoperation with stereotactic retargeting and placement of a new intracranial electrode. At reoperation, the connectors were placed subgaleally over the parietal region. Management of these cases has led to modifications in the operative procedure designed to improve the durability of DBS systems. The authors recommend that surgeons avoid placing the connection between the DBS electrode and the extension wire in the cervical region because patient movement can cause microfractures in the electrode. Such microfractures require intracranial revision, which may be associated with a higher risk of morbidity than the initial operation. The authors also recommend considering prophylactic relocation of the connectors from the cervical area to the subgaleal parietal region to decrease the risk of future DBS electrode fracture, which would necessitate a more lengthy procedure to revise the intracranial electrode.

Efficacy of unilateral deep brain stimulation of the thalamic ventralis intermedius nucleus in a patient with bipolar disorder associated with Klinefelter syndrome and essential tremor. Case report.

Deep brain stimulation (DBS) of the ventralis intermedius nucleus (Vim) is a safe and effective treatment for essential tremor. Bipolar disorder and essential tremor had each been reported to occur in association with Klinefelter syndrome but the three diseases have been reported to occur together in only one patient. The genetic basis and natural history of these disorders are not completely understood and may be related rather than coincidental. The authors report on a 23-year-old man with Klinefelter syndrome (47,XXY) and bipolar disorder who was treated successfully with unilateral DBS of the thalamic Vim for essential tremor.

Long-term deep brain stimulation in a patient with essential tremor: clinical response and postmortem correlation with stimulator termination sites in ventral thalamus. Case report.

Essential tremor can be suppressed with chronic, bilateral deep brain stimulation (DBS) of the ventralis intermedius nucleus (Vim), the cerebellar receiving area of the motor thalamus. The goal in this study was to correlate the location of the electrodes with the clinical efficacy of DBS in a patient with essential tremor. The authors report on a woman with essential tremor in whom chronic bilateral DBS directed to the ventral thalamus produced adequate tremor suppression until her death from unrelated causes 16 months after placement of the electrodes. Neuropathological postmortem studies of the brain in this patient demonstrated that both stimulators terminated in the Vim region of the thalamus, and that chronic DBS elicited minor reactive changes confined to the immediate vicinity of the electrode tracks. Although the authors could not identify neuropathological abnormalities specific to essential tremor, they believe that suppression of essential tremor by chronic DBS correlates with bilateral termination of the stimulators in the Vim region of the thalamus.

Guidelines for acute stroke treatment centers.

This article provides a description of the clinical infrastructure of a stroke center, including staffing requirements, technical capabilities, and recommended clinical protocols. These recommendations have been developed to assist in establishing new acute stroke centers that can deliver quality care and to aid in evaluating the relative strengths and weaknesses of existing stroke centers.

Targeting for thalamic deep brain stimulator implantation without computer guidance: assessment of targeting accuracy.

The authors assess the accuracy of targeting nucleus ventralis intermedius (Vim) with fast spin echo inversion recovery (FSE/IR) magnetic resonance imaging (MRI) in 18 successful deep brain stimulator (DBS) implants for medically refractory tremor. FSE/IR-MRI-derived coordinates are compared to the final coordinates employed for DBS lead placement, selected with intraoperative neurophysiology. The authors conclude that FSE/IR MRI is sufficiently reliable to serve as the sole means of anatomically targeting Vim for DBS lead placement. An independent computer workstation is not required for accurate targeting; however, intraoperative neurophysiology remains essential.

Ethical and institutional review board issues.

IRBs provide an important role in the protection of research subjects/patients. Research investigators have an inherent potential conflict of interest as health care professionals; as physicians, they are dedicated to promoting the welfare of individual patients, whereas as researchers, they seek knowledge that can be generalized and is applicable to persons other than the individual patient under study. The second goal may be in conflict with the first. IRBs have the paramount responsibility of protecting the rights and welfare of human research subjects. Although the IRB system is not perfect, conscientious IRBs reassure the public that the rights and welfare of human subjects are seriously considered by people who do not have a vested interest in the outcome of the research. By exercising their responsibilities, IRBs promote the protection of human subjects. IRB approval provides a significant affirmation of the scientific and ethical qualities of research, and therefore offers important validation to research and research investigators. IRBs, acting in accordance with the guiding principles of the Belmont Report and within the regulatory guidelines of 45.CFR.46, are intended to provide balance between society's interest in advancing scientific knowledge and the mandate to protect the rights and welfare of human subjects.

Relationship of 133Xe cerebral blood flow to middle cerebral arterial flow velocity in men at rest.

Cerebral blood flow (CBF) was measured by 133Xe clearance simultaneously with the velocity of blood flow through the left middle cerebral artery (MCA) over a wide range of arterial PCO2 in eight normal men. Average arterial PCO2, which was varied by giving 4% and 6% CO2 in O2 and by controlled hyperventilation on O2, ranged from 25.3 to 49.9 mm Hg. Corresponding average values of global CBF15 were 27.2 and 65.0 ml 100 g min-1, respectively, whereas MCA blood-flow velocity ranged from 42.8 to 94.2 cm/s. The relationship of CBF to MCA blood-flow velocity over the imposed range of arterial PCO2 was described analytically by a parabola with the equation: CBF = 22.8 - 0.17 x velocity + 0.006 x velocity2 The observed data indicate that MCA blood-flow velocity is a useful index of CBF response to change in arterial PCO2 during O2 breathing at rest. With respect to baseline values measured while breathing 100% O2 spontaneously, percent changes in velocity were significantly smaller than corresponding percent changes in CBF at increased levels of arterial PCO2 and larger than CBF changes at the lower arterial PCO2. These observed relative changes are consistent with MCA vasodilation at the site of measurement during exposure to progressive hypercapnia and also during extreme hyperventilation hypocapnia.

Bispectral analysis of visual interactions in humans.

Previous electrophysiological studies have demonstrated interactions between dichoptic visual stimuli presented to the same location in visual space. In this study, we used non-liner spectral analysis, in particular the bispectrum, to study interactions between the electrocerebral activity resulting from stimulation of the left and right visual fields. The stimulus consisted of two squares, one in each visual field, flickering at different frequencies. Bispectra, bichoherence and biphase were calculated for 8 subjects monocularly observing a visual stimulus. Both phase vs. frequency and biphase vs. frequency plots were made to determine weighted time delays from stimulus application to signal appearance in the EEG electrodes. Bispectral analysis reveals non-liner interactions between visual fields occurring with weighted delay times of 410 + / - 58 msec while non-interactive components propagated with weighted time delays of 202 + / - 39 msec. Evaluating these results in light of the predictions of various models, we were able to conclude that this interaction does not occur in the retina. These results illustrate how bispectral analysis can be a powerful tool in analyzing the connectivity of neural networks in complex systems. It allows different neuronal systems to be labeled with stimuli at specific frequencies, whose connections can be traced using frequency analysis of the scalp EEG.

Cerebral blood flow during spike-wave discharges.

We used the 133xenon method to assess cerebral blood flow (CBF) during generalized spike-wave discharges in a patient with an uncommon form of generalized epilepsy with persistent spike-wave discharges. CBF measurements were made under four conditions with repeated measures: normal EEG, continuous theta state, continuous spike-wave state at rest, and continuous spike-wave discharges during performance of a cognitive activation task. CBF was mildly reduced (5.7%) during the theta state and decreased further (12%) in the spike-wave state. Although globally diminished, CBF was less decreased in the frontal lobes and more decreased in the parietal lobes during spike-wave discharges. CBF increased to baseline levels during the cognitive activation task. The decrease in CBF suggested that the generalized spike-wave discharges caused a net decrease in cortical metabolic demand and neuronal activity. The differences in lobar CBF during spike-wave discharges may reflect lobar disparities in neuronal firing patterns. The theta state noted is novel and intermediate between normal and spike-wave.

Effects of emotional discrimination tasks on cerebral blood flow: regional activation and its relation to performance.

Facial discrimination tasks were applied as activation probes during physiologic neuroimaging ("neurobehavioral probes"). The stimuli pictured professional actors and actresses, posing degrees of happy and sad emotion. Cortical cerebral blood flow (CBF) was determined using the 133Xenon inhalation method during resting baseline, two emotional (happy from neutral and sad from neutral faces) and one nonemotional discrimination task (age). The three tasks produced CBF increase over baseline, which was greater in the right hemisphere (Task x Hemisphere interaction, p = .0001). There were regionally specific effects (Task x Region x Hemisphere interaction, p = .022). Relative to the age discrimination task, both emotion discrimination tasks were associated with greater right parietal activation. In addition, the happy discrimination task induced greater left frontal activation relative to the sad discrimination task. While overall magnitude of CBF increase did not show regionally specific correlations with performance, laterality did show such specificity. Sad discrimination performance correlated with greater right parietal activation, while performance on the happy discrimination task correlated with left frontal activation. Age discrimination performance correlated with higher activated right temporal CBF. These results support the hypothesis of right hemispheric involvement in facial processing and further suggest regionally specific hemispheric participation in happy and sad emotional discrimination. The study underscores the utility of performance measures for understanding the behavioral significance of activation effects in physiologic neuroimaging studies.

Lateralized increases in cerebral blood flow during performance of verbal and spatial tasks: relationship with performance level.

Physiologic neuroimaging studies have shown lateralized regional increase in brain activity during cognitive tasks, but the hypothesis that such changes are correlated with task performance has not been tested directly. We examined cerebral blood flow (CBF) changes induced by cognitive tasks in relation to performance. CBF was measured with the 133Xenon clearance method in 34 normal right-handed young (age < 30) volunteers during resting baseline and during the performance of a verbal analogies and a spatial line orientation test. Performance measures included "speed" and "power" estimates of both activation tasks. Resting CBF was moderately correlated with performance. The correlations were slightly higher with activated CBF for verbal but not spatial performance. The degree of increase (task-baseline) did not correlate with performance for either task. The highest and topographically specific correlations were obtained between laterality of CBF and verbal performance. Higher left hemispheric activation was correlated with verbal performance, and this correlation was significantly higher in the angular gyrus region. For the spatial task the correlations were with relatively higher right hemispheric activation but without regional specificity. The results underscore the importance of integrating behavioral performance data with physiologic measures in neuroimaging activation studies.

Effects of hypnosis on regional cerebral blood flow during ischemic pain with and without suggested hypnotic analgesia.

Using 133Xe regional cerebral blood flow (CBF) imaging, two male groups having high and low hypnotic susceptibility were compared in waking and after hypnotic induction, while at rest and while experiencing ischemic pain to both arms under two conditions: attend to pain and suggested analgesia. Differences between low and highly-hypnotizable persons were observed during all hypnosis conditions: only highly-hypnotizable persons showed a significant increase in overall CBF, suggesting that hypnosis requires cognitive effort. As anticipated, ischemic pain produced CBF increases in the somatosensory region. Of major theoretical interest is a highly-significant bilateral CBF activation of the orbito-frontal cortex in the highly-hypnotizable group only during hypnotic analgesia. During hypnotic analgesia, highly-hypnotizable persons showed CBF increase over the somatosensory cortex, while low-hypnotizable persons showed decreases. Research is supportive of a neuropsychophysiological model of hypnosis (Crawford, 1991; Crawford and Gruzelier, 1992) and suggests that hypnotic analgesia involves the supervisory, attentional control system of the far-frontal cortex in a topographically specific inhibitory feedback circuit that cooperates in the regulation of thalamocortical activities.

Reliability of regional cerebral blood flow activation to cognitive tasks in elderly normal subjects.

The assessment of cerebral blood flow (CBF) using noninvasive 133Xe techniques provides an indirect measurement of cortical metabolic activity. The utility of this method in longitudinal clinical studies depends on the stability and reproducibility of resting and activated flow measures. We evaluated CBF in a sample of 16 elderly normal subjects (aged 54-73 years) at rest and during task performance in two sessions separated by an average of 9 weeks. Resting global CBF was lower in the second session, a finding consistent with the known effects of habituation previously reported. Regionally specific activated CBF did not change with repeated measurements. The results provide evidence that the 133Xe technique is reliable and of potential utility in evaluating the effect of the natural course of brain disease, as well as the effects of therapeutic interventions on brain activity.

Decreases in frontal and parietal lobe regional cerebral blood flow related to habituation.

We previously reported decreased mean CBF between consecutive resting conditions, ascribed to habituation. Here we address the regional specificity of habituation over three consecutive flow studies. Regional CBF (rCBF) was measured in 55 adults (12 right-handed men, 12 right-handed women, 14 left-handed men, 17 left-handed women), with the 133Xe inhalation technique, during three conditions: resting, verbal tasks (analogies), and spatial tasks (line orientation). Changes in rCBF attributable to the cognitive tasks were eliminated by correcting these values to a resting equivalent. There was a progressive decrease in mean rCBF over time, reflecting habituation. This effect differed by region, with specificity at frontal (prefrontal, inferior frontal, midfrontal, superior frontal) and inferior parietal regions. In the inferior parietal region, habituation was more marked in the left than the right hemisphere. Right-handers showed greater habituation than did left-handers. There was no sex difference in global habituation, but males showed greater left whereas females showed greater right hemispheric habituation. The results suggest that habituation to the experimental setting has measurable effects on rCBF, which are differently lateralized for men and women. These effects are superimposed on task activation and are most pronounced in regions that have been implicated in attentional processes. Thus, regional decrement in brain activity related to habituation seems to complement attentional effects, suggesting a neural network for habituation reciprocating that for attention.

Facial emotion discrimination: I. Task construction and behavioral findings in normal subjects.

Facial discrimination tasks (age, happy-neutral, and sad-neutral) were developed to address the need for activation tasks that engage emotional processing and can be used during physiologic neuroimaging ("neurobehavioral probes"). The stimuli pictured professional actors and actresses who had been screened for asymmetric features. In experiment I, same-sex stimuli were used to examine the performance of normal subjects (24 men, 15 women) on the three tasks. Performance was better during the emotion-discrimination tasks than during the age-discrimination task, and males had higher sensitivity scores for the detection of sad emotion. However, experiment II showed that the sex of the stimulus interacts with the sex of the subject. Compared with female subjects, male subjects (n = 10) were selectively less sensitive to sad emotion in female faces. Female subjects (n = 10) were more sensitive overall to emotional expression in male faces than in female faces. Thus, men and women differed in performance depending on the sex of the facial stimulus.