[Intraoperative MRI and epilepsy surgery]. / IRM opératoire et chirurgie de l'épilepsie.

Intraoperative imaging, in particular intraoperative MRI, is a developing area in neurosurgery and its role is currently being evaluated. Its role in epilepsy surgery has not been defined yet and its use has been limited. In our experience with a compact and mobile low-field intraoperative MRI system, a few epilepsy surgeries have been performed using this technique. As the integration of imaging and functional data plays an important role in the planning of epilepsy surgery, intraoperative verification of the surgical result may be highly valuable. Therefore, teams that have access to intraoperative MRI should be encouraged to use this technique prospectively to evaluate its current relevance in epilepsy surgery.

Stereotactic comparison among cerebral blood volume, methionine uptake, and histopathology in brain glioma.

BACKGROUND AND PURPOSE: Vascularity, metabolism, and histologic grade are related in gliomas but the exact determinants of these relationships are not fully defined. We used image coregistration and stereotactic biopsies to regionally compare cerebral blood volume (CBV) and (11)C-methionine (MET) uptake measurements in brain gliomas and to assess their relationship by histopathologic examination. MATERIALS AND METHODS: Fourteen patients with brain gliomas underwent MR imaging, including dynamic susceptibility contrast-enhanced MR and positron-emission tomography (PET) using MET acquired in identical stereotactic conditions before biopsy. MR-based CBV maps were calculated and both CBV maps and PET images were coregistered to anatomic images. Sixty-five biopsy samples were obtained on trajectories targeted toward high MET uptake area. The following histopathologic features were semiquantified in each sample: mitotic activity, endothelial proliferation, cellular pleomorphism, and tumor necrosis. CBV and MET uptake values were measured in the biopsy area and normalized to contralateral white matter. CBV ratios were compared with MET uptake ratios, and both measurements were compared with histologic features of each sample. RESULTS: CBV ratios ranged from 0.08 to 10.24 (median = 1.73), and MET uptake ratios ranged from 0.30 to 4.91 (median = 1.67). There was a positive correlation between CBV ratios and MET uptake ratios (r = 0.65, P < .001). Both CBV and MET uptake ratios were found to be significantly related to endothelial proliferation and mitotic activity (P < .01). CONCLUSION: Within glial tumors, there is a local relationship between CBV and MET uptake measurements. Both provide indices of focal malignant activity.

Unconditional compensation: reducing the costs of disagreement about compensation for research subjects.

A central requirement of research involving humans is that people who participate as subjects should do so voluntarily. We argue that disagreements about the effect of offers of compensation on subjects' ability to participate voluntarily are likely to persist and to have high social costs. We propose a novel compensation practice--to pay potential subjects whether or not they participate--and argue that its implementation in some regions, including the Eastern Mediterranean Region, may reduce disagreement and thus mitigate such costs. We outline a research programme for assessing the potential of this practice to reduce costs.

[Transsphenoidal approach with low field MRI for pituitary adenoma]. / Apport de la résonance magnétique per-opératoire à bas champs dans la chirurgie de l'adénome hypophysaire.

INTRODUCTION: Appropriate evaluation of resection remains one of the major difficulties of surgical treatment of pituitary adenoma. The transsphenoidal approach does not allow direct visual control. Endoscopy provides useful information but may no distinguish well residual adenoma from the pituitary gland. Intraoperative MRI offers new perspectives for assessing the quality of resection. We report our experience with low field intraoperative MRI in surgical treatment of pituitary adenoma. POPULATION: Intraoperative MRI (Polestar N10, 30 patients and Polestar N20, 17 patients) was performed in 45 consecutive patients undergoing surgery for pituitary adenoma. Thirty-seven patients had a macroadenoma. Patients were in the prone position with the head fixed with a three-pin MRI-compatible headholder. METHOD: Coronal T1 MRI scans with enhancement were acquired pre and per operatively. We compared scans and surgical filling (complete removal). If there was a difference, a surgical control was undertaken. RESULTS: Intraoperative images were unavailable for two patients due to small size of the neck and the pituitary glands which were not in the middle in the field of view. For the others, the pituitary glands were in the field of view and the intraoperative scans could be used for comparison. For four patients, there was a discrepancy between surgeon filling and the intraoperative MRI. A control showed no residual adenoma but hemostatic tissue. CONCLUSION: Low field intraoperative MRI is an excellent technique for controlling the size of pituitary adenoma resection.

Ethics and psychiatric research: problems and justification.

The discussion of ethics in psychiatry continues to increase. Research in psychiatry, like all medical research, is of ethical concern because it often involves risks to subjects so that others may benefit. It also involves the allocation of monetary and human resources. In recent years these concerns have been brought to the forefront of professional and public attention. The authors consider the problem of justifying resource allocations and the risks involved in psychiatry research, survey some of the special problems faced by researchers in this field, and give a brief account of present government regulations that pertain to research ethics in psychiatry.

Regional methionine and glucose uptake in high-grade gliomas: a comparative study on PET-guided stereotactic biopsy.

UNLABELLED: Gliomas are regionally heterogeneous tumors. The local relationship between histologic features and radiotracer uptake evaluated by PET should therefore influence analysis and interpretation of PET results on gliomas. This study explored this local relationship as a result of PET guidance of stereotactic biopsies. METHODS: Local histology was confronted to the regional uptake of 18F-2-fluoro-2-deoxy-D-glucose (18F-FDG) and 11C-methionine (11C-MET) in 14 patients with high-grade glioma diagnosed during a procedure of PET-guided stereotactic biopsies. We analyzed the uptake of both tracers in regions of interest centered on the stereotactic coordinates of 93 biopsy samples. RESULTS: A semiquantitative analysis revealed a significant regional correlation between 11C-MET and 18F-FDG uptakes. Uptake of both tracers was significantly higher on the site of tumor samples showing anaplastic changes than in the rest of the tumor. Presence of necrosis in anaplastic areas of the tumor significantly reduced the uptake of 11C-MET. CONCLUSION: PET with 11C-MET and 18F-FDG may help to evaluate, in vivo, the metabolic heterogeneity of human gliomas. Anaplasia is a factor of increased uptake of both tracers, but microscopic necrosis in anaplastic areas influences their uptake differently. This finding probably relates to the differences in tracer uptake by non-neoplastic components of necrotic tumors. These results underline the complementary role of 18F-FDG and 11C-MET for the study of brain tumors and favors their use for stereotactic PET guidance of diagnostic or therapeutic procedures.

Coronary vasomotility and myocardial blood flow early after heart transplantation.

Serotonin constricts coronary arteries with endothelial dysfunction, a common abnormality in cardiac transplant recipients. To assess whether endothelial dysfunction is associated with myocardial blood flow (MBF) abnormalities, 24 patients were studied 1 to 12 months after transplantation. Serotonin in increasing doses (1, 10, and 20 micrograms/min for 2.5 min each) was infused into the coronary circulation. Diameters were measured by quantitative angiography. Fourteen patients (group A) had a pronounced artery constriction (diameter reduction > 40%), while in 10 other patients (group B), such a constriction was never reached. No patient had evidence of rejection and all had angiographically normal coronary arteries. MBF was measured at rest and after intravenous dipyridamole with dynamic nitrogen-13 ammonia positron emission tomography (PET). The resting MBF was higher in group A than in group B (94 +/- 12 vs 74 +/- 15 ml/min/100 g of tissue; p < 0.05). During dipyridamole, MBF was not significantly different (191 +/- 53 vs 184 +/- 64 ml/min/100 g; p = NS). Coronary flow reserve (the ratio of perfusion after dipyridamole to perfusion at rest) was significantly lower in group A than in group B (2.08 +/- 0.54 vs 2.66 +/- 0.57; p < 0.05). Thus, coronary hypersensitivity to serotonin in cardiac transplant recipients is associated with elevated resting MBF and reduced coronary flow reserve. Immune mechanisms inducing endothelial injuries and inflammation-related hyperemia may account for these abnormalities.

Early alterations of myocardial blood flow reserve in heart transplant recipients with angiographically normal coronary arteries.

BACKGROUND: The evaluation of the coronary reserve provides valuable information on the status of coronary vessels. Therefore, we studied with positron emission tomography (PET) and 13N-ammonia the myocardial blood flow (MBF) reserve in heart transplant recipients free of allograft rejection and with angiographically normal coronary arteries early after heart transplantation (HTx). The MBF reserve was calculated as the ratio between MBF after dipyridamole injection and basal MBF normalized for the rate-pressure product. METHODS: Patients were studied within 3 months (group A, n = 12) or more than 9 months (group B, n = 12) after HTx. Five patients have been studied both during the early and late period after HTx. Results were compared to those obtained in 7 normal volunteers (NL). RESULTS: Group A recipients had a significantly lower dipyridamole MBF (in ml/min/100 gr of tissue) than that of group B recipients (142+/-34 vs 195+/-59, p<0.05). This resulted in a significant decrease in MBF reserve early after HTx (group A: 1.82+/- 0.33) and a restoration to normal values thereafter (group B: 2.52+/- 0.53 vs NL: 2.62+/-0.51, p = ns). Separate analysis of 5 patients studied twice is consistent with these results. CONCLUSION: This study shows that in heart transplant recipients free of allograft rejection and with normal coronary angiography, MBF reserve is impaired early after HTx. Restoration within one year suggests that this abnormality does not represent an early stage of cardiac allograft vasculopathy.

Sex difference in 5HT2 receptor in the living human brain.

Serotonergic mechanisms are involved in gender-related behaviors and psychiatric conditions like aggression, eating disorders, depression, impulsivity or suicide. We studied gender differences in the living human brain type-2 serotonin receptor (5HT2r). Twenty-two healthy age-matched men and women were investigated using positron emission tomography and the selective radiotracer, 18F-labeled altanserin. Binding was quantified using a non-linear least-squares minimization procedure. We found significantly higher 5HT2r binding capacity in men than in women, especially in the frontal and cingulate cortices. Distinct liability for men and women to suffer from some psychiatric disorders responding to serotonergic agents may be related to differences in brain serotonin receptors.

In vivo binding of [18F]altanserin to rat brain 5HT2 receptors: a film and electronic autoradiographic study.

To further validate its use in positron emission tomography (PET), we studied the binding of [18F]altanserin, a specific 5HT2 radioligand, in the rat brain using in vivo autoradiography. Distribution of [18F]altanserin binding was comparable to the in vitro mapping of 5HT2 receptors reported in the literature. Selective displacers were used to test the reversibility and the selectivity of this radioligand. Specific binding of [18F]altanserin in the rat frontal cortex was quantified by direct counting with an electronic imaging system and by quantification on digitalized autoradiograms. Close results of about 30 pmol/g were obtained with both methods. Our data confirmed that [18F]altanserin is a valid tracer for 5HT2 receptors binding studies.

Prognostic value positron emission tomography with [18F]fluoro-2-deoxy-D-glucose in the low-grade glioma.

OBJECTIVE: The natural history of the supratentorial low-grade glioma (LGG) of the adult is variable, and its malignant transformation is hardly predictable. Because positron emission tomography with [18F]fluoro-2-deoxy-D-glucose (FDG) has prognostic value in high-grade gliomas, this study was designed to search for a possible relationship between glucose metabolism and risk of malignant evolution in LGGs. METHODS: Positron emission tomography with FDG was performed in 28 patients with LGGs (22 at the time of diagnosis and 6 after the diagnosis). A metabolic grading system based on the visual inspection of the positron emission tomographic images was used. RESULTS: In 19 patients, no area of FDG uptake higher than in the white matter was detected (metabolic Grade 1). All of those patients were alive at the end of the follow-up period. Only one of the patients presented a histological modification 7 months after the diagnosis. Nine patients presented areas of increased FDG uptake (metabolic Grade 2 or 3). Those areas were found in the tumor area in eight patients and in an area of radionecrosis in one. Of the nine patients with FDG "hot spots," six died, two had recurrence but were alive at the end of the follow-up period, and the patient with radionecrosis had no signs of recurrence. CONCLUSIONS: The presence of areas of increased FDG uptake in a histologically proven LGG predicts, in most cases, a deleterious evolution. This metabolic feature, detectable with a noninvasive procedure, may provide a clue to cellular changes, announcing malignant transformation in a tumor that retains the histological features of an LGG. Protocols with aggressive therapeutic strategies in this situation should be considered for evaluation.

Cerebral glucose metabolism and centrotemporal spikes.

The pathophysiology of regional glucose hypometabolism often associated with refractory, lesion-related, epilepsy is not well understood. In particular, the role of interictal spiking is controversial since animal models of partial epilepsy have shown that interictal spiking increases glucose metabolism. We addressed this question by studying with positron emission tomography (PET) and 18F-fluorodeoxyglucose (FDG) the regional cerebral metabolism in children with focal spiking unrelated to a brain lesion. Patients (11 children with benign childhood epilepsy with centrotemporal spikes (BCECS) and two children without seizures) had on EEG centrotemporal spikes which were either strictly unilateral (ten cases) or strongly predominant on one side (three cases). We looked for an asymmetry in the distribution of cerebral glucose metabolism in our group of patients using statistical parametric mapping (SPM). After spatial normalization, a reversed copy of the 13 scans was obtained, resulting in 26 scans which were assigned to two groups: a group with left-sided centrotemporal spikes and a group with right-sided centrotemporal spikes. Regional glucose metabolism was not statistically different in the two groups. This suggests that metabolic changes associated with interictal spiking cannot be demonstrated by PET with FDG in BCECS, and that this technique could be helpful for the differentiation between idiopathic and symptomatic cases of partial epilepsy in children.

Brain hypometabolism of glucose in low-weight depressed patients and in anorectic patients: a consequence of starvation?

As low-weight anorectic patients presented a global as well as a regional absolute hypometabolism of glucose, we investigated a population of ten age- and sex-matched low-weight depressed patients without anorexia nervosa to evaluate the impact of weight loss on cerebral glucose metabolism evaluated by positron emission tomography and [18F]-fluorodeoxyglucose. Ten age- and sex-matched healthy volunteers were used as controls. Absolute global and regional glucose activity was significantly lower in anorectic and low weight depressed patients than in control subjects. Anorectic patients compared with normal control subjects also showed lower relative metabolism of glucose in the parietal cortex. Within patients, absolute hypometabolism of glucose seems to be a consequence of low-weight while there is a positive correlation between absolute metabolism of glucose and body mass index.

Combined magnetic resonance imaging- and positron emission tomography-guided stereotactic biopsy in brainstem mass lesions: diagnostic yield in a series of 30 patients.

OBJECT: In the management of brainstem lesions, the place of stereotactic biopsy sampling remains debatable. The authors compared the results of magnetic resonance (MR) imaging, positron emission tomography (PET) scanning, and histological studies obtained in 30 patients who underwent MR imaging- and PET-guided stereotactic biopsy procedures for a brainstem mass lesion. METHODS: Between July 1991 and December 1998, 30 patients harboring brainstem mass lesions underwent a stereotactic procedure in which combined MR imaging and PET scanning guidance were used. Positron emission tomography scanning was performed using [18F]fluorodeoxyglucose in 16 patients, methionine in two patients, and both tracers in 12 patients. Definite diagnosis was established on histological examination of the biopsy samples. Interpretation of MR imaging findings only or PET findings only was in agreement with the histological diagnosis in 63% and 73% of cases, respectively. Magnetic resonance imaging and PET findings were concordant in 19 of the 30 cases; in those cases, imaging data correlated with histological findings in 79%. Treatment based on information derived from MR imaging was concordant with therapy based on histological findings in only 17 patients (57%). Combining MR imaging and PET scanning data, the concordance between the neuroimaging-based treatment and treatments based on histological findings increased to 19 patients (63%). In seven patients who underwent biopsy procedures with one PET-defined and one MR imaging-defined trajectory, at histological examination the PET-guided samples were more representative of the tumor's nature and grade than the MR imaging-guided samples in four cases (57%). In 18 patients PET scanning was used to define a biopsy target and provided a diagnostic yield in 100% of the cases. CONCLUSIONS: Although the use of combined PET and MR imaging improves radiological interpretation of a mass lesion in the brainstem, it does not accurately replace histological diagnosis that is provided by a stereotactically obtained biopsy sample. Combining information provided by MR imaging and PET scanning in stereotactic conditions improves the accuracy of targeting and the diagnostic yield of the biopsy sample; an MR imaging- and PET-guided stereotactic biopsy procedure is a safe and efficient modality for the management of mass lesions of the brainstem.

Positron emission tomography with injection of methionine as a prognostic factor in glioma.

OBJECT: Positron emission tomography with L-[methyl-11C]methionine (MET-PET) provides information on the metabolism of gliomas. The aim of this study was to determine the predictive value of MET-PET in the treatment of patients with gliomas. METHODS: Since 1992, 85 patients with a World Health Organization (WHO) classification-verified glioma underwent PET studies in which MET was injected before (74 cases) or after treatment (11 cases). Analysis of PET data was conducted by the same investigator using two scales: a qualitative visual grading scale and a quantitative scale (ratio between tumor uptake and normal brain uptake, classified on a seven-level scale). Uptake of MET was present in 98% of gliomas. The investigator judged this uptake to be moderate to very high based on visual inspection (qualitative scale). For all grades of gliomas, a visual grade of 3 was statistically associated with a shorter patient survival period (p < 0.005). The tumor/normal brain uptake ratio was significantly influenced by the histological grade of the tumor. A statistically poor outcome was demonstrated when this ratio was higher than a threshold of 2.2 for a WHO Grade II tumor and 2.8 for WHO Grade III tumor. For Grade II and III tumors, oligodendrogliomas had a higher uptake of MET than astrocytomas. CONCLUSIONS: Uptake of MET was present in 98% of the gliomas studied. A high uptake is statistically associated with a poor survival time. The intensity of MET uptake represents a prognostic factor for WHO Grade II and III tumors considered separately.

Cerebello-thalamo-cerebral diaschisis: a case report.

This reports positron emission tomography and [18F]fluorodeoxyglucose (PET-FDG) in a 69-year-old woman who underwent resection of the left cerebellar hemisphere for an acoustic neurinoma 17 years earlier. Functional impairment in cerebral cortical and subcortical structures was evaluated by studying the level of glucose metabolic activity at rest. Relative glucose metabolism was reduced in the prefrontal cortex contralateral to the cerebellar lesion. Contralateral thalamic metabolism was reduced significantly. The results suggest that this phenomenon of "crossed cerebello-thalamo-cerebral diaschisis" is related to a functional depression of the cerebello-thalamo-cortical pathway.

Basal ganglia and frontal lobe glucose metabolism. A reproducibility positron emission tomography study.

Positron emission tomography (PET) with 18F-fluoro-2-deoxy-D-glucose (FDG) is frequently used to study the metabolic correlates of movement and mental disorders. These studies generally focus on changes in the frontal cortex and the basal ganglia. The reproducibility of glucose metabolism estimates in these structures was tested in 13 normal subjects studied at rest using a standard and simple protocol. A reproducible dorsoventral metabolic gradient was demonstrated in the frontal cortex. Such a gradient was not present in the basal ganglia when the upper region of interest in the caudate nucleus, where the lower metabolic rate of glucose was probably attributable to partial volume effects, was not considered. Absolute values of glucose metabolic rates varied by 6.4 to 12.5% in the frontal cortex and by 6.8 to 14.7% in the basal ganglia. Variations in normalized values in the basal ganglia ranged from 4.0 to 8.6%. The number of subjects required to detect statistical differences in group comparison or in test-retest studies was calculated for different anticipated levels of change. With the variability detected in this experiment, less than 10 subjects were expected to be sufficient to detect a 15% change in most regions and in both types of studies.

Brain glucose metabolism in anorexia nervosa and affective disorders: influence of weight loss or depressive symptomatology.

Relationships between eating and affective disorders remain complex and unclear. Brain glucose metabolism of anorectic patients has been demonstrated to be reduced both globally and regionally, with a particular relative hypometabolism in the parietal cortex. To explore the possible influence of weight loss or depressive symptomatology on brain metabolism, we studied age- and sex-matched low-weight anorectic and depressed patients, normal-weight depressed patients, and healthy volunteers. Absolute global and regional glucose activity levels were reduced in low-weight patients, with the lowest values being found for anorectic patients. In relative values, anorectic patients showed a significant parietal hypometabolism in comparison to control subjects while they had higher metabolism in the caudate nuclei when compared with the other groups. Absolute hypometabolism of glucose seems to be a consequence of low weight as it was found in both low-weight anorectic and low-weight depressive patients. In addition, absolute glucose values were significantly correlated with body mass index in all subjects. Future positron emission tomographic studies in psychiatric patients should control for alimentary parameters.

Bioethics and anti-bioethics in light of Nazi medicine: what must we remember?

Only recently have historians explored in depth the role of the medical profession in Nazi Germany. Several recent works reveal that physicians joined the Nazi party in disproportionate numbers and lent both their efforts and their authority to Nazi eugenic and racist programs. While the crimes of the physician Mengele and a few others are well known, recent research points to a much broader involvement by the profession, even in its everyday clinical work. Analogous activities existed in the German legal and industrial communities; disruption of the medical ethic thus sprang from the broader social contexts of Nazi Germany. The new United States Holocaust Memorial Museum, now opening on the Mall in Washington, D.C., will have an opportunity to educate the public about both the great crimes at Auschwitz and other camps, and the gradual but thorough degradation of ethics in the German medical profession. From this presentation, contemporary bioethics can ponder the proper use of the Nazi analogy in bioethical debate.

Modern multimodal neuroimaging for radiosurgery: the example of PET scan integration.

Radiosurgery relies critically on medical imaging modalities. Leksell Gamma Knife (LGK) radiosurgery presents the highest requirements in terms of imaging accuracy as the treatment is applied in a single high-dose session with no other spatial control than medical imaging. The advent of new imaging modalities opens challenges for LGK planning strategies. The integration of stereotactic PET in LGK represents an example of such application of modern multimodality imaging in radiosurgery. Our experience consists of 80 patients treated with the combination of MR/CT and PET guidance. In order to analyze the specific contribution of PET findings, we developed a classification reflecting the strategy used to define the target volume. When combining PET and MR information, 102 target volumes were defined, because some patients presented with multiple lesions or multifocal tumor areas. Abnormal PET uptake was found in 86% of the lesions, and this information altered significantly the MR-defined tumor in 73%. In conclusion, integration of PET in radiosurgery provides additional information opening new perspectives for the treatment of brain tumors. The use of a standardized classification allows to assess the relative role of PET. A similar approach could be useful and may serve as a template for the evaluation of the integration of other new imaging modalities in radiosurgery.