[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.

Apparent diffusion coefficient and cerebral blood volume in brain gliomas: relation to tumor cell density and tumor microvessel density based on stereotactic biopsies.

BACKGROUND AND PURPOSE: MR imaging-based apparent diffusion coefficient (ADC) and regional cerebral blood volume (rCBV) measurements have been related respectively to both cell and microvessel density in brain tumors. However, because of the high degree of heterogeneity in gliomas, a direct correlation between these MR imaging-based measurements and histopathologic features is required. The purpose of this study was to correlate regionally ADC and rCBV values with both cell and microvessel density in gliomas, by using coregistered MR imaging and stereotactic biopsies. MATERIALS AND METHODS: Eighteen patients (9 men, 9 women; age range, 19-78 years) with gliomas underwent diffusion-weighted and dynamic susceptibility contrast-enhanced MR imaging before biopsy. Eighty-one biopsy samples were obtained and categorized as peritumoral, infiltrated tissue, or bulk tumor, with quantification of cell and microvessel density. ADC and rCBV values were measured at biopsy sites and were normalized to contralateral white matter on corresponding maps coregistered with a 3D MR imaging dataset. ADC and rCBV ratios were compared with quantitative histologic features by using the Spearman correlation test. RESULTS: The highest correlations were found within bulk tumor samples between rCBV and cell density (r=0.57, P < .001) and rCBV and microvessel density (r=0.46, P < .01). An inverse correlation was found between ADC and microvessel density within bulk tumor (r=-0.36, P < .05), whereas no significant correlation was found between ADC and cell density. CONCLUSION: rCBV regionally correlates with both cell and microvessel density within gliomas, whereas no regional correlation was found between ADC and cell density.

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.

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

11C-methionine PET for the diagnosis and management of recurrent pituitary adenomas.

PURPOSE: The detection of recurrent pituitary adenoma by magnetic resonance imaging (MRI) is rendered uncertain by the tissue remodelling that follows surgery or radiotherapy. We aimed to evaluate the contribution of PET with 11C-methionine (MET-PET) in the detection and management of recurrent pituitary adenoma. METHODS: Thirty-three patients with pituitary adenoma were evaluated postoperatively by MET-PET, either because of biological evidence of active residual tumour or because of MRI demonstration of non-functional adenoma growth. We studied 24 secreting adenomas and nine non-functional adenomas. RESULTS: In 30 patients, MET-PET detected abnormally hypermetabolic tissue. In 14 out of these, MRI did not differentiate between residual tumour and scar formation. In nine of these 14 cases, major therapeutic decisions were undertaken (radiosurgery and surgery). In another group of 16 patients, both MET-PET and MRI detected abnormal tissue. In one case, neither MRI nor MET-PET detected adenomatous tissue. Finally, abnormal tissue was detected in two patients on MRI solely. In these two cases, failure of MET-PET to reveal the adenoma was attributable to concomitant inhibitory therapy. The sensitivity of MET-PET and MRI varied as a function of the tumour type: all non-functional adenomas were localised by both modalities, while MET-PET detected all adrenocorticotropic hormone-secreting adenomas whereas MRI depicted only one of these eight lesions. Fifteen out of 17 patients treated by radiosurgery showed clinical improvement after treatment. CONCLUSION: We suggest that MET-PET is a sensitive technique complementary to MRI for the detection of residual or recurrent pituitary adenomas. It should gain a place in the efficient management of these tumours.

[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.

[Stereotactic mapping for radiosurgical treatment of vestibular schwannomas]. / Imagerie stéréotaxique de repérage dans le traitement radiochirurgical des schwannomes vestibulaires.

RATIONALE: As an exclusively image-guided surgery method, radiosurgery requires special attention in the choice of imaging modalities and acquisition parameters must be set with extreme care. METHODS: Quality control for resolution and accuracy of computed tomography (CT) scanners must be performed. Magnetic resonance imaging (MRI) distortions should be limited through magnetic field homogeneity adjustment (shimming) and acquisition parameters optimization. These inaccuracies should then be quantified through systematic combination of MRI and CT in the radiosurgery planning system. MRI pulse sequences selection criteria are defined by their ability to delineate tumor contrast enhancement and to image cranial nerves and vessels relative arrangement in the cistern and canal. Topography of the petrous structures, such as cochlea, vestibulum and facial nerve canal should be visible. Exact definition of real extension of the lesion at the end of the canal may require specific technical solutions. These technical requirements must be balanced depending on the lesion Volume staging (Koos), the treatment history (microsurgery), the clinical condition (hearing quality), the pathological context (NF2) or the age of the patient. RESULTS: T1-weighted Volumetric MRI pulse sequences (3D-T1) show a contrast enhanced signal that is useful for both the pons interface delineation in Koos III cases, and the canal ending in Ohata A and B. On the other hand, 3D-T1 introduce inaccuracies from magnetic susceptibility distortions and partial Volume effects. High resolution CISS T2-weighted Volumetric pulse sequences (3D-T2) give superior stereotaxic definition attributable to their better resolution (half a millimeter) minimizing partial Volume effects and to their lower magnetic susceptibility minimizing distortions. 3D-T2 allows direct nerve visualization. Moreover, this pulse sequence with contrast injection, show improved distinction between the pons and the nerves due to signal differences within the schwannomas. Fat saturation pulse sequences are of interest in post-microsurgery conditions. CONCLUSIONS: Radiology phase quality is critical and its complexity requires a high commitment to obtain satisfactory clinical results. Solelt the 3D-T1 MRI modality seems to us not to comply to minimum security criteria.

[Imaging for stereotaxic treatment of vestibular schwannomas. Error factors and corrections]. / Imagerie pour le traitement stéréotaxique des schwannomes vestibulaires. Facteurs d'erreur et corrections.

BACKGROUND AND PURPOSE: Gamma Knife radiosurgery treatment of vestibular schwannomas requires high accuracy for the prescribed dose definition and delivery. The main factors contributing to the error are the anatomical distortions of imaging modalities used for treatment planning. Imaging limitations and error factors are reviewed and detailed. Multimodality rationale for the delineation of vestibular schwannomas and surrounding structures are assessed. Quality control strategies are discussed and a distortion correction technique using a radiological phantom is presented. METHODS: Computed tomography is considered as the reference for spatial accuracy after appropriate scanner quality control using the stereotaxic fiducials system. Magnetic resonance imaging pulse sequence distortions are measured with a phantom designed for 3D non-linear local distortion evidence. A distortion correction transformation is computed from the phantom images and applied to the patient images. Results are verified using the stereotaxic fiducials system. RESULTS: Fiducials registration errors show spatial accuracy improvement, approaching computed tomography quality, after distortion correction of magnetic resonance images. CONCLUSIONS: The multimodal imaging approach for the dose planning of vestibular schwannomas radiosurgery treatment is relevant. Quality control of spatial accuracy for imaging modalities is mandatory and realistic in clinical routine.

[Dosimetric planning for radiosurgical treatment of vestibular schwannomas]. / Planification dosimétrique dans le traitement radiochirurgical des schwannomes vestibulaires.

Dosimetry planning is certainly the most typical neurosurgical instant in the radiosurgical procedure for the treatment of vestibular schwannomas (VS). Indeed, it is a key-moment in which the therapeutical choices will have a major influence on the clinical results, in terms of efficacy and safety. The therapist has to inform the patient about the rationale of the treatment, its limitations, the expected results, and the specific risks. Deep knowledge of the radiosurgical technique, of the principles of dosimetry, and of the therapist's personal experience, allows an a posteriori analytical study of the influence of the dosimetry therapeutic choices on the patient's outcome. Correlation between the preoperative therapeutic choices and the postoperative clinico-radiological information is mandatory to optimize therapeutic strategies. These therapeutic choices should be the result of a reflection integrating the clinical status of the patient, an understanding of the specific pathology of VS, awareness of the other therapeutic choices, and knowledge of radiological and surgical anatomy. The way a certain number of parameters will be defined during the dosimetry planning will have a major influence on the clinical results. This explains wide variability of clinical results from one operator to another, for the same radiological and radiosurgical tools. This emphasizes the need for specific and long-term training, associated with continuous education and a good knowledge of the very active literature.

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.

[The nuclear medicine department and the TEP/Biomedical Cyclotron unit]. / Le Service de Médecine Nucléaire et l'Unité TEP/Cyclotron Biomedical.

During the last 25 years, the clinical and experimental activity in nuclear medicine at Erasme hospital has been influenced by the implementation of positron emission tomography (PET) in 1990 as a method of brain functional investigation. The activity of the PET/biomedical cyclotron unit has been dedicated to various subjects in neurology, neurosciences, psychiatry, oncology and cardiology. This has been made possible by developments in radiochemistry. The radiochemistry laboratory has designed and produced original tracers such as 9-[(3-[18F]fluoro-1-hydroxy-2-propoxy)-methyl]guanine (FHPG), a tracer of viral thymidine kinase activity in gene therapy protocols. We have brought new applications of PET, such as its integration into stereotactic neurosurgical and radioneurosurgical techniques in order to improve their diagnostic and therapeutic performance in neurooncology. We have also conducted multiple studies on brain physiology and pathophysiology, in particular with the use of functional and metabolic brain mapping methods and the use of tracers of neurotransmission systems. The Department of nuclear medicine has also performed studies on bone metabolism and investigated in vivo imaging methods of infectious and immune processes.

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.

The Zeiss-MKM system for frameless image-guided approach in epidural motor cortex stimulation for central neuropathic pain.

OBJECT: Twelve patients (seven female, and five male, mean age 55.6 years) suffering from refractory central (ischemic/traumatic [eight cases]) and neuropathic pain (trigeminal neuropathy [four cases]) underwent surgery for the implantation of an epidural motor cortex stimulation (MCS) device in which the authors used a frameless neuronavigation system, the Zeiss-MKM microscope. METHODS: The authors assessed the spatial accuracy of the neuronavigation system and its potential contribution to improve the quality of targeting pain. In these patients, the positions of the central sulcus, defined by stereotactic magnetic resonance MR imaging, intraoperative somatosensory evoked potentials (SSEPs) and subdural visual verification, were correlated into the stereotactic neuronavigation planning procedure. The mean spatial accuracy of distance between (MR) imaging-defined and actual central sulcus was 2.4 mm (range 5-10 mm). The intraoperative SSEPdefined central sulcus was close to that defined by MR imaging (mean distance 6.4 mm). Although very precise, intraoperative SSEP recordings were impaired by artifacts and wave attenuation in six of the 12 patients. Stereotactic correlations between anatomical and functional data in the navigation system corrected final targeting in 10 of 12 cases. Pain relief was obtained in eight patients. Indeed, inappropriate targeting probably explains the reported variable success rate of MCS and certainly underestimates the actual efficacy. CONCLUSIONS: Since intraoperative SSEP monitoring has, for many years, been considered the standard procedure to approach motor target, the development of an accurate stereotactic image guidance system could help to increase the efficacy of MCS on the alleviation of pain. The excellent spatial accuracy provided by the Zeiss-MKM navigation system allows precise data correlations that represent a remarkable means to validate functional MR imaging as an alternative to SSEP. The authors believe that developing stereotactic image guidance with such a navigation system could improve the success rate of MCS.

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.

Statistical parametric mapping of regional glucose metabolism in mesial temporal lobe epilepsy.

We investigated statistical parametric mapping (SPM) use for positron emission tomography (PET) with [(18)F]fluorodeoxyglucose (FDG) data analysis in mesial temporal lobe epilepsy. The study involved 14 patients with temporal lobe epilepsy ultimately treated by anterior temporal lobectomy. Surgical outcome in terms of seizure control was favorable in 12 patients. Two different SPM approaches were designed to analyze each FDG-PET scan: a direct comparison with a control group (n = 27) and a search for significant interhemispheric asymmetry considering the asymmetry existing in the control group. Statistical inference was performed, first, without correction for multiple comparisons (making the hypothesis of temporal hypometabolism) and, second, after correction for multiple comparisons. Search for temporal interhemispheric asymmetry under the hypothesis of temporal hypometabolism was the most reliable SPM approach: hypometabolism was identified on the side chosen for resection in most cases (sensitivity, 71%; specificity, 100%) and was predictive of favorable postsurgical outcome in 90% of the patients. There was no false-positive result within the control group using this approach. After correction for multiple comparisons, SPM also identified in some patients temporal hypermetabolic areas as well as extratemporal cortical and subcortical hypometabolic areas on the side of resection but also on the contralateral side. In a further step, SPM was used for a group analysis of patients with favorable outcome after reversing scans when needed to set an identical lateralization in all patients. This analysis identified multiple ipsilateral temporal and extratemporal hypometabolic regions; when temporal metabolic changes were specifically assessed, the contralateral mesiotemporal region was found hypermetabolic, possibly as a manifestation of compensatory mechanisms in the presence of a unilateral epileptogenic lesion.

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.