Jean-Albert Lotterie

Language functional magnetic resonance imaging in preoperative assessment of language areas: correlation with direct cortical stimulation.

OBJECTIVEThe aim of this study was to analyze the usefulness of preoperative language functional magnetic resonance imaging (fMRI), by correlating fMRI data with intraoperative cortical stimulation results for patients with brain tumors. METHODSNaming and verb generation tasks were used, separately or in combination, for 14 right-handed patients with tumors in the left hemisphere. fMRI data obtained were analyzed with SPM software, with two standard analysis thresholds (P < 0.005 and then P < 0.05). The fMRI data were then registered in a frameless stereotactic neuronavigational device and correlated with direct brain mapping results. We used a statistical model with the fMRI information as a predictor, spatially correlating each intraoperatively mapped cortical site with fMRI data integrated in the neuronavigational system (site-by-site correlation). Eight patients were also studied with language fMRI postoperatively, with the same acquisition protocol. RESULTSWe observed high variability in signal extents and locations among patients with both tasks. The activated areas were located mainly in the left hemisphere in the middle and inferior frontal gyri (F2 and F3), the superior and middle temporal gyri (T1 and T2), and the supramarginal and angular gyri. A total of 426 cortical sites were tested for each task among the 14 patients. In frontal and temporoparietal areas, poor sensitivity of the fMRI technique was observed for the naming and verb generation tasks (22 and 36%, respectively) with P < 0.005 as the analysis threshold. Although not perfect, the specificity of the fMRI technique was good in all conditions (97% for the naming task and 98% for the verb generation task). Better correlation (sensitivity, 59%; specificity, 97%) was achieved by combining the two fMRI tasks. Variation of the analysis threshold to P < 0.05 increased the sensitivity to 66% while decreasing the specificity to 91%. Postoperative fMRI data (for the cortical brain areas studied intraoperatively) were in accordance with brain mapping results for six of eight patients. Complete agreement between pre- and postoperative fMRI studies and direct brain mapping results was observed for only three of eight patients. CONCLUSIONWith the paradigms and analysis thresholds used in this study, language fMRI data obtained with naming or verb generation tasks, before and after surgery, were imperfectly correlated with intraoperative brain mapping results. A better correlation could be obtained by combining the fMRI tasks. The overall results of this study demonstrated that language fMRI could not be used to make critical surgical decisions in the absence of direct brain mapping. Other acquisition protocols are required for evaluation of the potential role of language fMRI in the accurate detection of essential cortical language areas.

Frontal Assessment Battery is a marker of dorsolateral and medial frontal functions: A SPECT study in frontotemporal dementia

The objective of this study is to identify the cerebral regions that are assessed by the Frontal Assessment Battery (FAB). Using SPM voxel-based analysis, we looked for correlations between FAB performance and brain SPECT perfusion in 47 patients with the frontal variant of frontotemporal dementia (fv-FTD) recruited by the French FTD research network, a multicentre initiative of French University hospitals with expertise in the field of dementia. A significant correlation was found between FAB performance and perfusion in the medial and dorsolateral frontal cortex bilaterally, independently of age, gender and MMSE. No correlations were observed with orbital frontal or parietal perfusion, in spite of the presence of hypoperfusion in these areas, or with perfusion of any other cortical or subcortical region. These findings confirm that the FAB is an adequate tool for assessing functions related to the dorsolateral and medial frontal cortex, and is thus useful for the evaluation of diseases associated with frontal dysfunction.

Electrostimulation mapping of spatial neglect.

BACKGROUND Cortical and subcortical electrostimulation mapping during awake brain surgery for tumor removal is usually used to minimize deficits. OBJECTIVE To use electrostimulation to study neuronal substrates involved in spatial awareness in humans. METHODS Spatial neglect was studied using a line bisection task in combination with electrostimulation mapping of the right hemisphere in 50 cases. Stimulation sites were identified with Talairach coordinates. The behavioral effects induced by stimulation, especially eye movements and deviations from the median, were quantified and compared with preoperative data and a control group. RESULTS Composite and highly individualized spatial neglect maps were generated. Both rightward and leftward deviations were induced, sometimes in the same patient but for different stimulation sites. Group analysis showed that specific and reproducible line deviations were induced by stimulation of discrete cortical areas located in the posterior part of the right superior and middle temporal gyri, inferior parietal lobe, and inferior postcentral and inferior frontal gyri (P < .05). Fiber tracking identified stimulated subcortical areas important to spare as sections of fronto-occipital and superior longitudinal II fascicles. According to preoperative and postoperative neglect battery tests, the specificity and sensitivity of intraoperative line bisection tests were 94% and 83%, respectively. CONCLUSION In humans, discrete cortical areas that are variable in location between individuals but mainly located within the right posterior Sylvian fissure sustain visuospatial attention specifically toward the contralateral or ipsilateral space direction. Line bisection mapping was found to be a reliable method for minimizing spatial neglect caused by brain tumor surgery.

Radiochirurgie stéréotaxique des malformations artérioveineuses cérébrales

Radiosurgery as treatment for arteriovenous malformations has shown a good efficacy in reducing intracranial bleeding due to rupture. The choice of therapeutic modalities is based on evolutive risk and arteriovenous malformations volume, patient profile and risks stratification following therapeutic techniques (microsurgery, radiosurgery, embolization). Nidus size, arteriovenous malformations anatomical localization, prior embolization or bleeding, distributed dose are predictive factors for radiosurgerys good results and tolerance. This review article will highlight arteriovenous malformations radiosurgery indications and discuss recent irradiation alternatives for large arteriovenous malformation volumes.

An optimized calibration method for surface measurements with MOSFETs in shaped-beam radiosurgery.

Nowadays MOSFET dosimeters are widely used for dose verification in radiotherapy procedures. Although their sensitive area satisfies size requirements for small field dosimetry, their use in radiosurgery has rarely been reported. The aim of this study is to propose and optimize a calibration method to perform surface measurements in 6 MV shaped-beam radiosurgery for field sizes down to 18 × 18 mm(2). The effect of different parameters such as recovery time between 2 readings, batch uniformity and build-up cap attenuation was studied. Batch uniformity was found to be within 2% and isocenter dose attenuation due to the build-up cap over the MOSFET was near 2% irrespective of field size. Two sets of sensitivity coefficients (SC) were determined for TN-502RD MOSFET dosimeters using experimental and calculated calibration; the latter being developed using an inverse square law model. Validation measurements were performed on a realistic head phantom in irregular fields. MOSFET dose values obtained by applying either measured or calculated SC were compared. For calibration, optimal results were obtained for an inter-measurement time lapse of 5 min. We also found that fitting the SC values with the inverse square law reduced the number of measurements required for calibration. The study demonstrated that combining inverse square law and Sterling-Worthley formula resulted in an underestimation of up to 4% of the dose measured by MOSFETs for complex beam geometries. With the inverse square law, it is possible to reduce the number of measurements required for calibration for multiple field-SSD combinations. Our results suggested that MOSFETs are suitable sensors for dosimetry when used at the surface in shaped-beam radiosurgery down to 18 × 18 mm(2).

OC-0308: Identification of significant biological subvolumes from MRI in pediatric ependymoma related to treatment outcome

Despite late complications related to radiation therapy, RT remains a standard component of treatment among pediatric patients. The current aim of many pediatric clinical trials is to reduce dose and volume of irradiation to decrease side effects without affecting the rate of local control using multimodality treatment. Recent advances in radiotherapy technology contribute also to improve therapeutic ratio thanks to better conformal dose distribution and avoidance of surrounding critical structures. Integration of multimodal imaging in target delineation, use of CT for treatment planning (3D conformal radiation therapy) and immobilization devices have significantly decreased clinical and planning target volume margins. Intensity modulated radiation therapy could be particularly useful in cases of complex and large volume closed to critical structures. While high dose to neighboring structures can be selectively decreased by the means of IMRT, low dose is raised in the rest of the body with theoretical increased risk of secondary malignancies or unexpected toxicities related to irradiation of very sensitive organs at risk located at distance of target volume. Number of prospective studies comparing IMRT to 3D CRT is low. However available data suggest that IMRT provided local control equivalent to 3D CRT with favorable short term toxicity profile and reduction of some sequelae. No excess of second tumor is described but followup is still limited. Concerning strategies for management of internal target movement due to respiratory motion, the more widespread modality in pediatric radiotherapy is 4-dimensional CT for radiation. Other techniques such as active breathing control or respiratory gating is not widely widespread because their use is conditioned by collaboration ability and patient age. Up to now stereotactic radiation therapy has been mainly used in childhood for intracranial benign disease by neurosurgeon. However development of non-invasive repositioning system and LINAC dedicated to stereotactic irradiation gives the opportunity of hypofractionated treatment of metastasis or recurrence in previously irradiated field with minimal impact of quality of live in palliative setting. With high precision techniques, reproducibility in daily set-up becomes more critical to prevent geographic misses and image-guided RT (IGRT) has become a common practice of care for children as for the adults. One of the most applied IGRT technique is cone-beam computed tomography (CBCT). A limitation in use of CBCT among pediatric population is the extra dose deposit to critical structures witch is higher in children than in adults. Because of potential of yielding a secondary cancer at long term, it is essential to adapt scanning protocol when CBCT is applied to pediatric cancer patients routinely.

In-vivo dosimetry for field sizes down to 6 × 6 mm2 in shaped beam radiosurgery with microMOSFET

The aim of this study is to evaluate microMOSFET as in-vivo dosimeter in 6 MV shaped-beam radiosurgery for field sizes down to 6 × 6 mm2. A homemade build-up cap was developed and its use with microMOSFET was evaluated down to 6 × 6 mm2. The study with the homemade build-up cap was performed considering its influence on field size over-cover occurring at surface, achievement of the overall process of electronic equilibrium, dose deposition along beam axis and dose attenuation. An optimized calibration method has been validated using MOSFET in shaped-beam radiosurgery for field sizes from 98 × 98 down to 18 × 18 mm2. The method was detailed in a previous study and validated in irregular field shapes series measurements performed on a head phantom. The optimized calibration method was applied to microMOSFET equipped with homemade build-up cap down to 6 × 6 mm2. Using the same irregular field shapes, dose measurements were performed on head phantom. MicroMOSFET results were compared to previous MOSFET ones. Additional irregular field shapes down to 8.8 × 8.8 mm2 were studied with microMOSFET. Isocenter dose attenuation due to the homemade build-up cap over the microMOSFET was near 2% irrespective of field size. Our results suggested that microMOSFET equipped with homemade build-up cap is suitable for in-vivo dosimetry in shaped-beam radiosurgery for field sizes down to 6 × 6 mm2 and therefore that the required build-up cap dimensions to perform entrance in-vivo dosimetry in small-fields have to ensure only partial charge particle equilibrium.

Dedicated linear accelerator radiosurgery for classical trigeminal neuralgia: a single-center experience with long term follow-up

BACKGROUND During the past decades, stereotactic radiosurgery, and Gamma Knife in particular, has proved its safety and efficacy for drug-resistant classic trigeminal neuralgia. However, few large series exist using linear accelerator (LINAC) reporting long-term follow-up. METHODS Between 2006 and 2015, 301 patients were treated by LINAC at our institution. The prescribed radiation dose was 90 Gy at the far anterior target. Clinical response was defined using the Barrow Neurological Institute scale. We considered grades I and IIIa as a successful response. Mean duration of follow-up was 54.6 months (range, 12-132 months). RESULTS Two hundred and seventy-three patients (90.7%) were initially pain free, and 28 patients (9.3%) were unchanged. The actuarial probabilities of maintaining pain relief with or without medication (Barrow Neurological Institute grade I and IIIa) at 0.5, 1, 2, 4, 5, and 10 years were 88.7%, 85.0%, 76.1%, 68.8%, 65.8%, and 48.1%, respectively. Hypesthesia was present in only 26.2% of patients (very bothersome, 0.3%). No anesthesia dolorosa was reported. The actuarial probabilities of maintaining pain relief without further surgery at 0.5, 1, 2, 4, and 5 years were 99.3%, 98.3%, 95.8%, 91.0%, and 89.7%, respectively. Among all treated patients, 86.5% were satisfied by the procedure and would undergo stereotactic radiosurgery again. CONCLUSIONS Stereotactic radiosurgery with dedicated LINAC is associated with high rates of long-term pain relief, with minimal invasiveness and rare complications. LINAC is a possible therapeutic alternative for drug-resistant trigeminal neuralgia and could be proposed to selected patients as the first intention therapy, among other surgical solutions.

Familiarity and recollection vs representational models of medial temporal lobe structures: A single-case study

ABSTRACT Although it is known that medial temporal lobe (MTL) structures support declarative memory, the fact these structures have different architectonics and circuitry suggests they may also play different functional roles. Selective lesions of MTL structures offer an opportunity to understand these roles. We report, in this study, on JMG, a patient who presents highly unusual lesions that completely affected all MTL structures except for the right hippocampus and parts of neighbouring medial parahippocampal cortex. We first demonstrate that JMG shows preserved recall for visual material on 5 experimental tasks. This finding suggests that his right hippocampus is functional, even though it appears largely disconnected from most of its MTL afferents. In contrast, JMG performed very poorly, as compared to control subjects, on 7 tasks of visual recognition memory for single items. Although he sometimes performed above chance, neither familiarity nor recollection appeared fully preserved. These results indicate that extrahippocampal structures, damaged bilaterally in JMG, perform critical operations for item recognition; and that the hippocampus cannot take over that role, including recollection, when these structures are largely damaged. Finally, in a set of 3 recognition memory tasks with scenes as stimuli, JMG performed at the level of control participants and obtained normal indices of familiarity and recollection. Overall, our findings suggest that the right hippocampus and remnants of parahippocampal cortex can support recognition memory for scenes in the absence of preserved item‐recognition memory. The patterns of dissociations, which we report in the present study, provide support for a representational account of the functional organization of MTL structures. HIGHLIGHTSUnusual pattern of medial temporal lobe lesion.Dissociation between preserved recall but impaired recognition memory for single item.Impaired recognition memory for single item, preserved recognition memory for scenes.Familiarity and recollection results did not easily fit with dual‐process accounts of the MTL but in this case are in agreement with representational account of the MTL.

OC-0615: Voxel-based perfusion normalisation in GBM patients included in a phase I-II trial of RT/Tipifarnib combination

2.7%, p= 0.041). In the Capox-RT group, 85.7% (191/223) patients received radiotherapy on schedule and 74.9% (166/223) with concurrent chemotherapy on schedule, as did 94.1% (238/253) and 92.1% (233/353) in the Cap-RT group, respectively. Grade 3-4 acute toxicity was observed in 38.1% of patients in the Capox-RT group and in 29.2% in the Cap-RT group (p = 0.041). Grade 3–4 tenesmus was more common in the Capox-RT group than in the Cap-RT group (5.4% vs. 2.0%), as were grade 3–4 nausea (2.2% vs. 0%), grade 3–4 vomiting (1.8% vs. 0%), and grade 3–4 fatigue (3.1% vs. 0.4%). Conclusions: The interim analysis revealed that inclusion of oxaliplatin into capecitabine based postoperative chemoradiotherapy was feasible and could decrease cumulative locoregional recurrence rate for patients with locally advanced rectal cancer.