Morphological redifferentiation in a malignant astrocytic tumor after gamma knife radiosurgery

2002 ◽  
Vol 97 ◽  
pp. 627-630 ◽  
Author(s):  
György T. Szeifert ◽  
Nicolas Massager ◽  
Jacques Brotchi ◽  
Marc Levivier

Object. The purpose of this study was to demonstrate positron emission tomography (PET), histological, and immunohistochemical data supporting the notion of morphological redifferentiation in a malignant astrocytic tumor after gamma knife radiosurgery (GKS). Methods. The 11C- methionine-PET activity, Ki-67 labeling index (LI), and p53 protein expression were examined using immunohistochemical methods to assess tumor proliferative capacity. Tissue samples were obtained before and after radiosurgery in a patient with a malignant (Grade III) cerebellar astrocytoma. Positron emission tomography scans obtained 5.5 months following radiosurgery were suggestive of decreased tumor proliferative capacity and radionecrosis. Histological examination of tumor tissue removed 42 months before GKS was characteristic of a diffuse Grade III astrocytoma in every part of the resected tumor. Similar material removed 6 months after GKS was consistent with a Grade II astrocytoma in the great majority of the resected tumor. Conclusions. Histopathological examination showed positive phenotypic modification (redifferentiation) consistent with a Grade II astrocytoma in the majority of tumor specimens after radiosurgery. After GKS both the Ki-67 LI and p53 reaction decreased considerably as did 11C methionine uptake. Because p53 is one of the essential genes involved in the radiation response, mutations induced by the ionizing effect of gamma rays might promote partial repair of this gene's tumor suppressor function.

2001 ◽  
Vol 95 (5) ◽  
pp. 746-750 ◽  
Author(s):  
Olivier De Witte ◽  
Ilan Goldberg ◽  
David Wikler ◽  
Sandrine Rorive ◽  
Philippe Damhaut ◽  
...  

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.


2002 ◽  
Vol 97 ◽  
pp. 542-550 ◽  
Author(s):  
Marc Levivier ◽  
David Wikler ◽  
Nicolas Massager ◽  
Philippe David ◽  
Daniel Devriendt ◽  
...  

Object. The authors review their experience with the clinical development and routine use of positron emission tomography (PET) during stereotactic procedures, including the use of PET-guided gamma knife radiosurgery (GKS). Methods. Techniques have been developed for the routine use of stereotactic PET, and accumulated experience using PET-guided stereotactic procedures over the past 10 years includes more than 150 stereotactic biopsies, 43 neuronavigation procedures, and 34 cases treated with GKS. Positron emission tomography—guided GKS was performed in 24 patients with primary brain tumors (four pilocytic astrocytomas, five low-grade astrocytomas or oligodendrogliomas, seven anaplastic astrocytomas or ependymomas, five glioblastomas, and three neurocytomas), five patients with metastases (single or multiple lesions), and five patients with pituitary adenomas. Conclusions. Data obtained with PET scanning can be integrated with GKS treatment planning, enabling access to metabolic information with high spatial accuracy. Positron emission tomography data can be successfully combined with magnetic resonance imaging data to provide specific information for defining the target volume for the radiosurgical treatment in patients with recurrent brain tumors, such as glioma, metastasis, and pituitary adenoma. This approach is particularly useful for optimizing target selection for infiltrating or ill-defined brain lesions. The use of PET scanning contributed data in 31 cases (93%) and information that was specifically utilized to adapt the target volume in 25 cases (74%). It would seem that the integration of PET data into GKS treatment planning may represent an important step toward further developments in radiosurgery: this approach provides additional information that may open new perspectives for the optimization of the treatment of brain tumors.


2000 ◽  
Vol 92 (6) ◽  
pp. 1009-1015 ◽  
Author(s):  
Seiji Yamamoto ◽  
Weiyu Teng ◽  
Shigeru Nishizawa ◽  
Takeharu Kakiuchi ◽  
Hideo Tsukada

Object. The hydroxyl radical scavenger (±)-N,N′-propylenedinicotinamide (AVS) has been shown to ameliorate the occurrence of vasospasm following experimental subarachnoid hemorrhage (SAH) and to reduce the incidence of delayed ischemic neurological deficits (DINDs) in patients with SAH. The authors investigated whether prophylactic administration of AVS could improve cerebral blood flow (CBF) and cerebral glucose utilization (CGU) following SAH in rats.Methods. Anesthetized rats were subjected to intracisternal injection of blood (SAH group) or saline (control group). Either AVS (1 mg/kg/min) or saline (vehicle group) was continuously injected into the rat femoral vein. Forty-eight hours later, positron emission tomography scanning was used with the tracers 15O-H2O and 18F-2-fluoro-d-glucose to analyze quantitatively CBF and CGU, respectively, in the frontoparietal and occipital regions (12 regions of interest/group).In SAH rats receiving only vehicle, CBF decreased significantly (p < 0.05, Tukey's test) and CGU tended to decrease, compared with values obtained in control (non-SAH) rats receiving vehicle. In rats that were subjected to SAH, administration of AVS significantly (p < 0.05, Tukey's test) improved CBF and CGU in both the frontoparietal and occipital regions compared with administration of vehicle alone.Conclusions. Prophylactic administration of AVS improves CBF and CGU in the rat brain subjected to SAH, and can be a good pharmacological treatment for the prevention of DINDs following SAH.


1999 ◽  
Vol 91 (4) ◽  
pp. 605-609 ◽  
Author(s):  
Petra M. Klinge ◽  
Georg Berding ◽  
Thomas Brinker ◽  
Wolfram H. Knapp ◽  
Madjid Samii

Object. In this study the authors use positron emission tomography (PET) to investigate cerebral blood flow (CBF) and cerebrovascular reserve (CVR) in chronic hydrocephalus.Methods. Ten patients whose mean age was 67 ± 10 years (mean ± standard deviation [SD]) were compared with 10 healthy volunteers who were 25 ± 3 years of age. Global CBF and CVR were determined using 15O—H2O and PET prior to shunt placement and 7 days and 7 months thereafter. The CVR was measured using 1 g acetazolamide. Neurological status was assessed based on a score assigned according to the methods of Stein and Langfitt.Seven months after shunt placement, five patients showed clinical improvement (Group A) and five did not (Group B). The average global CBF before shunt deployment was significantly reduced in comparison with the control group (40 ± 8 compared with 61 ± 7 ml/100 ml/minute; mean ± SD, p < 0.01). In Group A the CBF values were significantly lower than in Group B (36 ± 7 compared with 44 ± 8 ml/100 ml/minute; p < 0.05). The CVR before surgery, however, was not significantly different between groups (Group A = 43 ± 21%, Group B = 37 ± 29%). After shunt placement, there was an increase in the CVR in Group A to 52 ± 37% after 7 days and to 68 ± 47% after 7 months (p < 0.05), whereas in Group B the CVR decreased to 14 ± 18% (p < 0.05) after 7 days and returned to the preoperative level (39 ± 6%) 7 months after shunt placement.Conclusions. The preliminary results indicate that a reduced baseline CBF before surgery does not indicate a poor prognosis. Baseline CBF before shunt placement and preoperative CVR are not predictive of clinical outcome. A decrease in the CVR early after shunt placement, however, is related to poor late clinical outcome, whereas early improvement in the CVR after shunt placement indicates a good prognosis.


2005 ◽  
Vol 102 (5) ◽  
pp. 927-929 ◽  
Author(s):  
Michail Plotkin ◽  
Hubertus Hautzel ◽  
Bernd Joachim Krause ◽  
Stephan Mohr ◽  
Karl Josef Langen ◽  
...  

✓ The authors report on a patient suffering from acute Lyme borreliosis who underwent two consecutive [18F]fluorodeoxyglucose—positron emission tomography (FDG-PET) studies demonstrating the course of the disease. The first FDG-PET study revealed markedly increased glucose metabolism in the brainstem, matching exactly the signal abnormalities exhibited on magnetic resonance images and indicating a brainstem tumor. A second PET scan demonstrated no abnormality in this region, thus reflecting clinical remission following antibiotic therapy. Data in the present case indicate that hypermetabolic findings on FDG-PET studies in the brainstem region should be regarded with caution and that neuroborreliosis must be considered as a possible differential diagnosis.


2000 ◽  
Vol 92 (1) ◽  
pp. 64-69 ◽  
Author(s):  
Karen D. Davis ◽  
Ethan Taub ◽  
Frank Duffner ◽  
Andres M. Lozano ◽  
Ronald R. Tasker ◽  
...  

Object. Deep brain stimulation (DBS) of the sensory thalamus has been used to treat chronic, intractable pain. The goal of this study was to investigate the thalamocortical pathways activated during thalamic DBS.Methods. The authors compared positron emission tomography (PET) images obtained before, during, and after DBS in five patients with chronic pain. Two of the five patients reported significant DBS-induced pain relief during PET scanning, and the remaining three patients did not report any analgesic effect of DBS during scanning. The most robust effect associated with DBS was activation of the anterior cingulate cortex (ACC). An anterior ACC activation was sustained throughout the 40 minutes of DBS, whereas a more posteriorly located ACC activation occurred at a delay after onset of DBS, although these activations were not dependent on the degree of pain relief reported during DBS. However, implications specific to the analgesic effect of DBS require further study of a larger, more homogeneous patient population. Additional effects of thalamic DBS were detected in motor-related regions (the globus pallidus, cortical area 4, and the cerebellum) and visual and association cortical areas.Conclusions. The authors demonstrate that the ACC is activated during thalamic DBS in patients with chronic pain.


2002 ◽  
Vol 96 (2) ◽  
pp. 263-268 ◽  
Author(s):  
Arun K. Gupta ◽  
Peter J. Hutchinson ◽  
Tim Fryer ◽  
Pippa G. Al-Rawi ◽  
Dot A. Parry ◽  
...  

Object. The benefits of measuring cerebral oxygenation in patients with brain injury are well accepted; however, jugular bulb oximetry, which is currently the most popular monitoring technique used has several shortcomings. The goal of this study was to validate the use of a new multiparameter sensor that measures brain tissue oxygenation and metabolism (Neurotrend) by comparing it with positron emission tomography (PET) scanning. Methods. A Neurotrend sensor was inserted into the frontal region of the brain in 19 patients admitted to the neurointensive care unit. After a period of stabilization, the patients were transferred to the PET scanner suite where C15O, 15O2, and H215O PET scans were obtained to facilitate calculation of regional cerebral blood volume, O2 metabolism, blood flow, and O2 extraction fraction (OEF). Patients were given hyperventilation therapy to decrease arterial CO2 by approximately 1 kPa (7.5 mm Hg) and the same sequence of PET scans was repeated. For each scanning sequence, end-capillary O2 tension (PvO2) was calculated from the OEF and compared with the reading of brain tissue O2 pressure (PbO2) provided by the sensor. In three patients the sensor was inserted into areas of contusion and these patients were eliminated from the analysis. In the subset of 16 patients in whom the sensor was placed in healthy brain, no correlation was found between the absolute values of PbO2 and PvO2 (r = 0.2, p = 0.29); however a significant correlation was obtained between the change in PbO2 (ΔPbO2) and the change in PvO2 (ΔPvO2) produced by hyperventilation in a 20-mm region of interest around the sensor (ρ = 0.78, p = 0.0035). Conclusions. The lack of correlation between the absolute values of PbO2 and PvO2 indicates that PbO2 cannot be used as a substitute for PvO2. Nevertheless, the positive correlation between ΔPbO2 and ΔPvO2 when the sensor had been inserted into healthy brain suggests that tissue PO2 monitoring may provide a useful tool to assess the effect of therapeutic interventions in brain injury.


1999 ◽  
Vol 90 (3) ◽  
pp. 478-483 ◽  
Author(s):  
Richard G. Bittar ◽  
André Olivier ◽  
Abbas F. Sadikot ◽  
Frederick Andermann ◽  
Roch M. Comeau ◽  
...  

Object. To investigate the utility of [15O]H2O positron emission tomography (PET) activation studies in the presurgical mapping of primary somatosensory cortex, the authors compared the magnitude and location of activation foci obtained using PET scanning with the results of intraoperative cortical stimulation (ICS).Methods. The authors used PET scanning and vibrotactile stimulation (of the face, hand, or foot) to localize the primary somatosensory cortex before surgical resection of mass lesions or epileptogenic foci affecting the central area in 20 patients. With the aid of image-guided surgical systems, the locations of significant activation foci on PET scanning were compared with those of positive ICS performed at craniotomy after the patient had received a local anesthetic agent. In addition, the relationship between the magnitude and statistical significance of blood flow changes and the presence of positive ICS was examined.In 22 (95.6%) of 23 statistically significant (p < 0.05) PET activation foci, spatially concordant sites on ICS were also observed. Intraoperative cortical stimulation was positive in 40% of the PET activation studies that did not result in statistically significant activation. In the patients showing these results, there was a clearly identifiable t-statistic peak that was spatially concordant with the site of positive ICS in the sensorimotor area. All PET activation foci with a t statistic greater than 4.75 were associated with spatially concordant sites of positive ICS. All PET activation foci with a t statistic less than 3.2 were associated with negative ICS.Conclusions. Positron emission tomography is an accurate method for mapping the primary somatosensory cortex before surgery. The need for ICS, which requires local anesthesia, may be eliminated when PET foci with high (> 4.75) or low (< 3.20) t-statistic peaks are elicited by vibrotactile stimulation.


2000 ◽  
Vol 93 (supplement_3) ◽  
pp. 233-238 ◽  
Author(s):  
Marc Levivier ◽  
David Wikier ◽  
Serge Goldman ◽  
Philippe David ◽  
Thierry Metens ◽  
...  

✓ The purpose of this study was to assess the use of positron emission tomography (PET) as a stereotactic planning modality for gamma knife radiosurgery (GKS). The authors developed and validated a technique for fiducial marker imaging, importation, and handling of PET data for integration into GammaPlan planning software. The clinical feasibility in applying this approach to a selected group of patients presenting with recurrent glial tumors or metastases was evaluated. Positron emission tomography data can be integrated into GammaPlan, allowing a high spatial accuracy, as validated using a phantom. Positron emission tomography data were successfully combined with magnetic resonance (MR) images to define the target volume for the radiosurgical treatment of patients with recurrent glioma or metastasis. This approach may contribute to optimizing target selection for infiltrating or ill-defined brain lesions. Because PET is also useful for the pretreatment and follow-up evaluation, the use of stereotactic PET in these patients can enable an accurate comparison of PET-based metabolic data with MR-based anatomical data. This could give a better understanding of the metabolic changes following radiosurgery. The ability to use PET data in GKS represents a crucial step toward further developments in radiosurgery, as this approach provides additional information that may open new perspectives for the optimization of the treatment of brain tumors.


2004 ◽  
pp. 381-389 ◽  
Author(s):  
Timothy D. Solberg ◽  
Nzhde Agazaryan ◽  
Bryan W. Goss ◽  
Magnus Dahlbom ◽  
Steve P. Lee

Object. The authors hypothesized that the efficacy of intensity-modulated radiation therapy (IMRT) can be enhanced by selectively increasing the radiation dose to the biologically active positron emission tomography (PET)-documented positive tumor subregions while simultaneously maintaining the overall clinically established target dose. Methods. The authors undertook a feasibility study to evaluate IMRT PET/computerized tomography (CT) protocol for boost treatment in selected cancer patients. Prior to treatment, FDG-PET and CT scans were acquired using an integrated PET/CT scanner, ensuring accurate correlation between image sets. After acquisition, tumor volume and objects-at-risk (OARs) were outlined on the CT scans; any PET-positive tumor subregions were similarly outlined. Daily dosages of 1.8 to 2 Gy were prescribed to tumor volume and the margin whereas additional dosages of 10 to 20% were delivered to PET-positive subregions. Dosage—volume histogram—derived constraints were used in inverse planning to specify the desired dose to one or more PET-positive tumor subregions, CT-delineated tumor volume, and OARs. The IMRT treatment was delivered using a micromultileaf collimator. Simultaneous integrated boost radiation was successfully delivered using IMRT with PET/CT planning. Excellent dose conformality was achieved in the tumor volume and the dose to PET-positive tumor subregions was increased while minimizing the dose to OARs. Conclusions. When coupled with IMRT, PET/CT scanning allows dose escalation to biologically active subregions within the tumor volume. Further study is needed to determine if dose escalation to FDG-PET—active sites correlates with improved treatment outcome. Finally, in extracranial sites, PET scanning should only be performed with a dedicated PET/CT device because present image fusion technologies are inadequate for accurately registering deformable objects.


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