The Risk of Haemorrhage after Image Guided Stereotactic Biopsy of Intra-Axial Brain Tumours – A Prospective Study

Summary  Objective. To analyze prospectively the frequency and the risk of symptomatic and asymptomatic haemorrhage after image guided stereotactic biopsy of intra-axial brain tumours.  Methods. The study was conducted within a time frame of 24 months (April 1998–April 2000). 326 patients (150 males, 176 females; mean age 56.8 years) were included and 345 computerized tomography (CT)-guided stereotactic biopsies were performed/supervised by a specialized stereotactic neurosurgeon. A modified Riechert Stereotaxy System and a workstation for multiplanar trajectory planning were used in all patients. Serial biopsies (median, 5 samples) were done with small forceps (diameter 1 mm), smear preparations of the biopsy specimens were intra-operatively examined. Frequency, size, and location of any detectable bleeding were analyzed by post-biopsy CT-scan investigation. For risk estimation, logistic regression analysis was performed. The chi-square statistic was used for comparative analysis of the study results with available data from the literature.  Results. A conclusive tissue diagnosis could be achieved in 98%. Overall treatment morbidity was 3.1%. There was no mortality. Haemorrhage related morbidity was 0.9%. Age, Karnofsky score, mass effect of the tumour, tumour histology, tumour location and the number of specimens taken did not have any prognostic significance. The clinically silent bleeding rate was 9.6% and more often seen in patients with high grade gliomas (p=0.03). Both the silent and non-silent bleeding rate were significantly lower as compared to available prospective data in the literature. (p<0.01).  Conclusion. Using multiplanar image guided trajectory planning, small biopsy forceps and intra-operative smear preparations the risk of major haemorrhage related morbidity after stereotactic brain tumour biopsy is extremely low (<1%) in experienced hands.     

The effective application of segmental image fusion in spinal radiosurgery for improved targeting of spinal tumours

Purpose  As a result of experiences of failed image fusion, an improved protocol for effective CT and MRI image fusion was developed. Image fusion is a critical part of image-guided stereotactic radiosurgery (IG-SRS) and greatly influences the accurate measurement of gross tumour volume (GTV) and optimal dosimetry. Avoidance of any positional discrepancy is vital for optimal image fusion and results in improved targeting, which improves clinical results. This paper describes a protocol for effective image fusion and how it impacted on the clinical outcome of stereotactic radiosurgery for spinal tumours. Methods  Fused MRI/CT images from 20 patients were examined and compared. A protocol for fusing images from thin slice MR images and CTs was developed for improved identification and measurement of tumour volume. Differences in individual GTV values both before and after image fusion were evaluated. The effectiveness of tumour targeting was also assessed by comparing discrepancies in individual and overall GTV values. Results  Differences in mean GTVs using either CT or MRI alone compared with the mean found through combined CT/MR image fusion showed a difference of 30.5 ± 4.8% and 14.5 ± 3.3% respectively. Additionally, the median GTV values from CT- and MR-based imaging were 11.64 ± 7.8 cm³ and 11.72 ± 6.6 cm³ vs 14.06 ± 8.0 cm³. Median GTV from CT–MR fusion was 14.06 ± 8.0 cm³. Improved information provided by the fused images enabled us to prescribe more effective dosages, as the fused images gave more accurate information about tumour se due to better delineation of tumour perimeters. Conclusions  This protocol provides improved visualisation of spinal tumours and enables better treatment planning. Segmented image fusion was shown to provide significant advantages for planning stereotactic radiosurgery. Fused images provided more precise and accurate data and allowed better targeting of tumours, with improved tumour coverage that resulted in better clinical outcomes.     

Review of radiosurgery of pineal parenchymal tumors. Long survival following 125-iodine brachytherapy of pineoblastomas in 2 cases.

OBJECTIVE: The aim of the present work is to report the volumetric changes of tumor in two pineoblastoma patients treated with stereotactic interstitial irradiation and to present a review on radiosurgery of pineal parenchymal tumors. METHODS: Two of our patients with pineoblastoma were treated with CT and image-fusion guided 125-iodine brachytherapy. The tumor volumes were determined with outlined contours on planning and control CT/MRI images and were compared. RESULTS: Until January 2006, there were 61- and 58-month follow-up periods in the two cases. 56 and 53 months after irradiation the MRI images showed significant tumor shrinkage. In case 1 tumor volume was 0.76 cm (3) on the last control MRI image, compared to the 2.87 cm (3) at the time of interstitial irradiation, which means 73% shrinkage. In case 2, tumor volume measured with the last control MRI examination was 0.29 cm (3), which represents 77% shrinkage of the original tumor volume. In both Cases 1 and 2, PET examinations using (11)C-methionine showed no active tumor mass 56 and 53 months following brachytherapy. CONCLUSION: Two successful treatments of pineoblastoma are reported. The interstitial irradiation of the tumors decreased their volumes significantly. The CT and image fusion-guided 125-iodine stereotactic brachytherapy can be planned well dosimetrically and is surgically precise.     

Open MRI-Guided Neurosurgery

Summary  Objectives. A number of different image-guided surgical techniques have been developed during the past decade. None of these methods can provide the surgeon with information about the dynamic changes that occur intra-operatively.  Material and Method. The first vertical open 0.5 T MRI-scanner for intra-operative MRI-guided neurosurgery in Germany was installed at the University of Leipzig during the summer 1996. Since autumn 1996 a number of surgical procedures including biopsies (n=31), craniotomies (n=32), transsphenoidal procedures (n=8) and interstitial lasertherapies (n=3) have been performed using intra-operative MR image guidance.  Results. The development of MR-compatible and MR-safe non-magnetic instruments and components had to be solved. Specific surgical instruments were developed to perform biopsies, craniotomies, microsurgical tumour resections and transsphenoidal procedures in the 0.5-T open MRI. Several components required adaptation including the head holder, the stereotactic navigation device, the high speed drill, the suction unit, the ultrasonic aspirator, the bipolar coagulation, the laser probe and the surgical microscope. All these newly developed technical features enable the neurosurgeon to perform a large number of surgical procedures under direct control and guidance of intra-operative MR imaging. In contrast to frame-based for framless navigation systems, intra-operative MRI provides accurate and immediate information during the progress of surgery. These intra-operative images allow definitive localization and targeting of the lesions and accommodate anatomical changes that may occur during surgery.  Conclusion. Intra-operative MRI is helpful for navigation as well as determining of tumour margins to achieve a complete and safe resection of intracranial lesions. Complications related to the surgical procedure are reduced and the risk of neurological deterioration due to tumour removal and postoperative complications is minimized. It can be concluded that the intra-operative application of interventional MRI technology may represent a major step forward in the field of neurosurgery.     

Mechanical Accuracy of a New Stereotactic Guide

Summary ? Objective. A new stereotactic guide using a navigational computer is developed for stereotactic procedures. In order to compare the mechanical accuracy of the guide to frame based systems, an error analysis study was designed.  Methods. A biopsy procedure was simulated using a phantom model. Targets with known co-ordinates in a three-dimensional Cartesian co-ordinate system were positioned inside the skull model. A biopsy needle was inserted along computer set trajectories from three different entry points. The position of the biopsy needle in the co-ordinate system was measured. Distance from needle tip to target was calculated and defined as the error of the system for each trial. The results were statistically analyzed for precision and biasedness.  Results. A total of 242 accuracy measurements (182 on two MRI scans, 60 on one CT scan) were carried out. Mean incision length along the trajectories was 59 mm. Mean error using MRI scans was 3.8 mm and for the CT scan 2.9 mm. The error of the stereotactic computer was found to be 1.0 mm with both MR and CT imaging. The main cause of error for the MRI based trials was distortion of the magnetic field.  Conclusion. The results indicate a stereotactic system with high degree of accuracy. This is confirmed by a clinical study of 39 biopsies where all tumours were reached. MRI affected the mechanical accuracy significantly due to distortion of the magnetic field. The accuracy is comparable to other studies performed on both stereotactic computers and frame based systems.     

Accuracy of stereotactic localisation with magnetic resonance compared to CT scan: experimental findings

Summary  Background. Stereotactic localisation of proper targets can be obtained with Magnetic Resonance imaging (MRI), pending correction of the well-known inaccuracy of MRI in reproducing exact geometrical dimension. The aim of the experimental work was to determine the real extent of the MRI distortion and to correct it.  Methods. PVC phantoms and fixed human brains were used as target simulators; stereotactic targeting was obtained with CT and MRI; the results were compared and, finally, the real stereotactic values were measured on a commercial stereotactic device. To optimise MRI targeting it was necessary to abate the “chemical-shift”, to modify the head-coil receiver (tuning the “off-resonance” frequencies) and to correct the targeting directly on the images (especially for the Y axis values); careful quality control and environmental tests were also necessary to maintain good performances along the time.  Results. 172 measurements were carried out using both CT, plain X-ray and MRI on PVC phantom. The values obtained from CT were considered as reference. Significant geometrical accuracy was found with CT targeting, except for the Z co-ordinate, due to the slice thickness. Mean value differences between the targets on MRI and their real geometric position are about 1 mm on X and Z axises and about 2 mm on Y axis. Similar results were obtained on fixed brains, where absolute values of X and Y co-ordinates of the simulators were measured using a millimetre grid placed over the brain slice.  Interpretation. Experimental findings concerning stereotactic targeting with MRI suggest accuracy adequate for clinical practice, even when extreme geometrical precision is required, such as in radiosurgery or functional stereotaxy. Careful quality control and intensive experimental setting of the MRI device are mandatory to obtain satisfactory results.     

Metastatic Brain Tumours from Oesophageal Carcinoma: Neuro-Imaging and Clinicopathological Characteristics in Japanese Patients

Summary  Background. Since metastatic brain tumours from esophageal carcinoma are essentially rare, previous reports have not determined the common neuro-radiological findings and its clinical aspects.  Findings. We report the neuro-imaging and clinicopathological features of our 8 metastatic brain tumours from an esophageal site. Histologically, 6 of our 8 patients had squamous cell carcinoma and 2 had small cell carcinoma, a rare variant form. Both histological types mainly exhibited cystic lesions with a thin enhanced rim on magnetic resonance images (MRI, 4 of 6 squamous cell carcinomas and 1 of 2 small cell carcinomas). Combination therapy (irradiation and chemotherapy) after surgical treatment, the number of metastatic brain tumours, and the interval between their appearance and the diagnosis of the primary lesion could be prognostic factors in our series.  Interpretation. Among Japanese, the vast majority of primary esophageal cancers are squamous cell carcinomas. Therefore, MRI findings of a cystic tumour with a thin enhanced rim may alert one to the possibility of a metastatic brain tumour from the esophagus.     

Whole-Body [18F]FDG PET in the Management of Metastatic Brain Tumours

Summary Background To determine its roles in the diagnosis and the systemic evaluation of metastatic brain tumours, whole-body positron emission tomography (PET) using [¹⁸F]FDG was performed in 20 consecutive patients. Methods  All patients were thought to be suffering or needing to be differentiated from metastatic brain tumours. Nine patients had multiple brain lesions; six were older and showed a rim-enhancing lesion with surrounding oedema; seven had homogeneously enhancing periventricular lesion(s) on computed tomography (CT) and/or magnetic resonance (MR) imaging, thought to be central nervous system lymphomas. Two patients had skull mass(es) and two patients had a solid mass suspected to be, respectively, a haemorrhagic metastasis and a metastatic malignant melanoma. All of them received whole-body [¹⁸F]FDG PET and conventional systemic work-up for metastasis in order to compare the results of the two methods. Results  Metastatic brain tumours were diagnosed on whole-body [¹⁸F]FDG PET in eleven patients who had extracranial and intracranial hypermetabolic lesions. In nine of these, a conventional work-up also detected primary lesions which on whole-body [¹⁸F]FDG PET were seen to be hypermetabolic foci. Systemic lymph node metastases were detected by whole-body [¹⁸F]FDG PET only in two patients and histological diagnosis was possible by biopsy of lymph nodes rather than of brain lesions. In the remaining nine patients who had only intracranial hypermetabolic foci, histological diagnosis was made by craniotomy or stereotactic biopsy. It was confirmed that seven of nine patients were suffering from a primary brain tumour and two from metastatic carcinoma. None of the nine showed evidence of systemic cancer on conventional work-up. Histological diagnoses of the primary brain tumours were four cases of primary central nervous system lymphoma and one each of multifocal glioblastoma, Ewing's sarcoma, and cavernous angioma.  Patients felt no discomfort during the whole-body [¹⁸F]FDG PET procedure and there were no complications. The false negative rate in [¹⁸F]FDG PET and in conventional work-up was 15.4% and 30.7% respectively. There were no false positives on either [¹⁸F]FDG PET or conventional work-up. Conclusion  It is suggested that whole-body [¹⁸F]FDG PET is a safe, reliable, and convenient method for the diagnosis and systemic evaluation of patients thought to be suffering or needing to be differentiated from a metastatic brain tumour.     

Open MRI-Guided Microsurgery of Intracranial Tumours. Preliminary Experience Using a Vertical Open MRI-Scanner

Summary ? Objectives. A number of different image-guided surgical techniques have been developed during the past decade. None of these methods can provide the surgeon with information about the dynamic changes that occur intra-operatively. The development of open configurated MRI-scanners leads to new perspectives in the intra-operative management and resection control of intracranial tumours.  Material and Method. Using a vertical open 0.5 T MRI-scanner for intra-operative MR image guided neurosurgery, forty-four patients (20 female/24 male) with different intracranial tumours have been operated on since August 1997. The patients ranged in age from 20 to 70 years (mean±standard deviation=47.2±15.9 ys).  Results. In 36 (82%) of 44 patients the tumours were completely removed with the aid of MR image-guidance. In 8 cases (18%) complete removal was not achieved. Postoperatively 6 (14%) of 44 patients developed neurological deficits which were transient in 5 cases (paresis, dysphasia). In these patients the tumours were located in or near eloquent brain areas (sensorimotor cortex/speech center).  Conclusion. Intra-operative MRI is helpful for navigation as well as determining of tumour margins to achieve a complete and safe resection of intracranial lesions. Complications related to the surgical procedure are reduced and the risk of neurological deterioration due to tumour removal and postoperative complications is minimized. It can be concluded that the intra-operative application of interventional MRI technology may represent a major step foreward in the field of neurosurgery.     

Open MRI-Guided Microsurgery of Intracranial Tumours in or Near Eloquent Brain Areas

Summary  Objectives. Preservation of brain function while maximizing resection is the main aim of brain tumour surgery. The purpose of this study was to evaluate the efficacy of intra-operative magnetic resonance imaging to preserve brain function in patients with tumours in or near eloquent brain areas.  Methods and Material. Between August 1997 and January 1999 fifty-eight craniotomies for intracranial tumours or vascular malformations have been performed at the University of Leipzig using a 0.5 T superconducting MR system “SIGNA SP” (General Electric Medical Systems, USA). In 32 of these patients (15 male/17 female) with intracranial tumours, located in or near eloquent brain areas (sensorimotor cortex/speech center), 34 craniotomies were performed using the image guidance of the interventional MRI.  Results. Using intra-operative MRI criteria, complete tumour removal could be achieved in 28 (82%) of 34 procedures. In 3 patients only subtotal tumour removal was possible, because the residual tumour was not visible on the intra-operative MR images, but could be identified on early diagnostic follow-up MR-scans. In 3 patients, incomplete tumour resection was performed in order to avoid neurological impairment. In these patients intra-operative MR-images revealed residual tissue abnormalities involving or encroaching on deep brain structures or motor/language cortex. Pre-operative neurological status was unchanged in 24 patients (70%), worsened in 4 patients (12%) and improved in 6 patients (18%).  Conclusions. Intra-operative MRI is helpful for navigation as well as to demonstrate the tumour margins to achieve a complete and safe resection of intracranial lesions located in or near eloquent brain areas. It enables an image based functional monitoring of the brain which is critical for motor, sensory or language function. Complications related to the surgical procedure are reduced and the risk of neurological deterioration due to tumour removal and postoperative complications is minimized.     

Changes of Cerebral Blood Flow Following Dexamethasone Treatment in Brain Tumour Patients. A Xe/CT Study

Summary  Background. It is not exactly known how dexamethasone improves the function of brain that is affected by tumour. Whether and in what sense dexamethasone influences cerebral blood flow has rarely been addressed and previous investigations have yielded inconsistent results.  Method. Stable xenon-enhanced computed tomography (Xe/CT) was used to assess the regional cerebral blood flow (rCBF) in 67 patients with supratentorial primary and secondary brain tumours. rCBF studies were done at least once prior to resection or stereotactic biopsy of the tumours. In nine patients repeated studies before surgery and in 15 patients additional studies after resective surgery were obtained. Dexamethasone was administered according to the clinical needs before surgery and systematically after surgery. Of the preoperative studies 30 were obtained before and 47 during dexamethasone treatment. The rCBF data were analysed upon correlations with daily dose, cumulative dose, and duration of dexamethasone treatment. Moreover, individual courses before and after surgery were examined.  Findings. Mainly inverse correlations were found between the treatment parameters, particularly the daily dose of dexamethasone, and rCBF. Only in the subgroup of glioblastoma patients, a positive correlation was found of both duration and cumulative dose of dexamethasone with rCBF in oedema. Serial observations of individual patients confirmed the above findings, yet with possible exceptions. After tumour resection a clear improvement of rCBF was regularly observed.  Interpretation. The beneficial effect of dexamethasone is not attributed to an increase of cerebral blood flow, because rather decreases of rCBF are mostly observed.     

A Stereotactic Device for Experimental Rat and Mouse Irradiation Using Gamma Knife Model B – Technical Note

Summary  Background. For radiobiological experiments using the Gamma Knife model B, we constructed a stereotactic device to irradiate rat and mouse brains and verify the absorbed dose at the target using thermoluminescence dosimetry and a head phantom.  Methods. Our stereotactic device is primarily designed for rats using the fixation principles of a stereotactic atlas. A head-fixation adapter for a mouse was constructed to enable targeted irradiation of mouse brains. We built simple phantoms to simulate rat and mouse heads. We placed thermoluminescent dosimeters at various positions on the phantom for dose measurements. Dose planning employed the Leksell Gamma Plan version 4.11 software, assuming a spherical skull geometry for all calculations.  Findings. The measurements demonstrated that the actual absorbed dose agreed with our calculations within the errors of thermoluminescence dosimetry and the accuracy of our irradiation technique and dose calculations.  Interpretation. This device provides an accurate method for irradiating rat and mouse brains using the Gamma Knife model B.     

A New Procedure for Frameless Computer Navigated Stereotaxy

Summary ? Objective. Stereotactic procedures using frame-based systems have become well established in neurosurgery. Later, stereotactic computers have provided the neurosurgeon with a broader range of applications. A new, frameless stereotactic guide which utilizes the navigational abilities of a computer has been developed. This clinical study evaluates the accuracy and safety of the system when applied for puncture of tumours and abscesses in the cerebrum.  Methods. Using a frameless setup 36 patients were operated on for a total of 39 intracranial processes over a period of two years. Three patients were operated on twice. Computer data, time of surgery, anesthesia, complications, tumour localization and tissue examinations were recorded.  Results. Biopsies were obtained from all lobes of the cerebrum and a diagnosis established in all cases except two. Mean age and total range was 52 years and 15–82 years, respectively. Median time of surgery was approximately 60 minutes including positioning of the patient and the registration process on the stereotactic computer. Local anesthesia was used for 25 operations and general anesthesia for 14 operations. There was one postoperative abscess formation in a previously immunosupressed patient and a per-operative epileptic seizure caused by electrocoagulation of the dura in a second patient.  Conclusions. Based on this clinical study a new procedure for obtaining stereotactic biopsies of intracranial processes is introduced. All tumours were successfully reached with two cases of complications.     

Interstitial brachytherapy for low-grade cerebral gliomas: Analysis of results in a series of 36 cases

Summary The results obtained with interstitial brachytherapy in thirty-six low-grade cerebral gliomas (2 pilocytic astrocytomas, 23 astrocytomas and 11 oligodendrogliomas) are reported (mean follow-up: 75 months, range 37–159). All tumours were situated in locations which did not call for surgical removal as the treatment of choice. Their volume ranged from 4 to 82 cc (m=32); the Karnofsky performance status (KPS) of the treated patients lay between 0.60 and 0.90.The sources utilized (Iridium-192 in 32 cases and Iodine-125 in 4) were implanted permanently in 22 patients and temporarily in 14, using the Talairach stereotactic apparatus. The mean peripheral dose was 89.7 Gy for the permanent implants and and 42.8 Gy with a rate of 32.05 cGy/h for the temporary implants. External beam irradiation was added for tumour volumes greater than 35 cc (19 cases) on a second target volume extending 2 cm beyond the tumoural borders treated with interstitial irradiation.The survival estimates for the entire group showed a probability of 82.9% at 60 months, of 56.8% at 96, 39.4% at 120 (m.s.t.: 112 months). The quality of life in the treated patients was satisfactory, KPS never falling below a mean score of 0.70. The extent of the target volume turned out to be the most significant factor influencing survival at the multivariate analysis. Severe neurological impairment due to radionecrosis occurred in 4 patients (11%), three of them requiring surgical decompression. Target volume and radiation dose showed a direct correlation with the risk of radionecrosis at the regression analysis, the critical values being 35 cc and 100 Gy (permanent implants) or 50 Gy (42 cGy/h, temporary implants) respectively. The analysis of the results indicates that, even though many questions still remain open, brachytherapy can represent a valid alternative to surgery for tumours not suitable for surgical removal.Study partially supported by a grant from the Italian Ministry of University and of Scientific and Technological Research.     

Pineal region tumours treated with interstitial brachytherapy with low activity sources (192-iridium)

Summary Three patients with tumours of the pineal region underwent interstitial Ir-192 brachytherapy. Histological diagnoses were obtained in all patients, by stereotactic biopsy and included one germinoma, one mixed pineoblastoma/pineocytoma, and one astrocytoma grade III. Our approach to pineal region neoplasms is first to decide whether sterotactic biopsy or surgery should be performed. When a pineal lesion is thought to be benign on the basis of imaging, such as benign teratoma, surgery is performed to resect the entire lesion. When a definitive diagnosis is not possible, stereotactic biopsy is performed to obtain a histological diagnosis for treatment planning, using a Brown-Roberts-Wells (BRW) stereotactic apparatus with computed tomography (CT) or magnetic resonance imaging (MRI). When a lesion is malignant and localized, stereotactic implantation of catheters for interstitial brachytherapy is performed simultaneously. Radioactive Ir-192 seeds are inserted into the catheters and maintained for 5–10 days to give 36 Gy of irradiation at the tumour periphery. Sequential CT scans and MRI after treatment revealed tumour disappearance in two patients with germinoma and high grade astrocytoma and tumour reduction in the patient with mixed pineoblastoma/pineocytoma. No significant morbidity or mortality occurred in any of these patients after stereotactic biopsy and brachytherapy. The technique and the advantages of this therapeutic approach to selected pineal region tumours are described and discussed.     

Demonstration of the Optic Pathway in Sellar/Juxtasellar Tumours with Visual Disturbance on MR Imaging

Summary  Objective. To prospectively compare the demonstration of the intracranial optic pathway in patients with sellar/juxtasellar tumours and with clinical evidence of visual disturbance using either spoiled gradient recalled acquisition in steady state (SPGR) or conventional spin echo (CSE) T1-weighted imaging.  Materials and Methods. We studied 108 patients with sellar/juxtasellar tumours presenting visual disturbance. Visualization of the optic pathway (nerves, chiasm, tracts) was compared between CSE T1-weighted coronal image and SPGR coronal image. In 18 patients, SPGR imaging was performed before and after administration of Gd-DTPA and visualization of the optic pathway was compared.  Results. On CSE T1-weighted coronal images of 108 patients with visual disturbance, the rates for visualization of the optic nerves, chiasms and tracts were 50%, 77.8% and 89.8% respectively. In contrast, on SPGR coronal image the rates were 80.6%, 96.3% and 92.6% respectively. The rates of visualization of the optic pathway were greater in non-enhanced that in those with enhancement. The rates of visualization in patients with recurrent tumours were less than those in patients with primary tumours. The rate of visualization of optic nerves in patients with meningioma was less than in patients with pituitary adenoma, craniopharyngioma or Rathke cleft cyst.  Conclusion. The rate of visualization of optic pathway structures on SPGR imaging (without enhancement) is greater than that on CSE T1-weighted imaging. It is important to understand the accurate position of the optic pathways with using new MR modality especially in surgical planning for lesions around the sella turcica.     

Prognostic Value of Vascular Endothelial Growth Factor and its Receptors Flt-1 and Flk-1 in Astrocytic Tumours

Summary  Background. Vascular endothelial growth factor (VEGF)/vascular permeability factor (VPF) is an important regulator of angiogenesis and vascular permeability.  Method. We examined immunohistochemically expressions of VEGF and its corresponding receptors Flt-1 and Flk-1 in a series of 50 astrocytic tumours, and correlated their expressions with the degree of angiogenesis, brain edema and prognosis.  Findings. There were significant relationships between VEGF, Flk-1 expressions and glioma malignancy grading, intratumoural vascularity and peritumoural brain edema, respectively. Patients with VEGF positive low grade astrocytoma and glioblastoma multiforme had a significantly shorter mean overall survival time than those with negative tumours (P=0.0010 and 0.0180, respectively). Flk-1 is also a significant prognostic factor within each tumour grade, which has a negative impact on overall survival. Additionally, overexpression of VEGF and Flk-1 were significantly associated with earlier recurrence in patients with low grade astrocytomas (P=0.0018 and 0.0240, respectively).  Interpretation. It is possible to subcategorize each grade of astrocytic tumours based on their VEGF and Flk-1 staining pattern, which may be crucial in predicting the biological behavior of tumours and thus provide useful information with regard to adequate treatment.     

Craniocervical junction instability: instrumentation and fusion with titanium rods and sublaminar wires. Effectiveness and failures in personal experience

Summary.  Background: The aim of the study was to evaluate the effectiveness, pitfalls and failures of instrumentation and fusion with titanium wires and rods in 12 h patients with craniovertebral junction instability.  Methods: Among nine adult patients (mean age 48.11 years) with craniovertebral junction instability, four had basilar impression, three metastatic disease, one rheumatoid arthritis and one Down's syndrome. Three children (mean age 7.33 years) with genetic (Down's syndrome, 2 cases) and metabolic (mucopolisaccarydoses type IV, i.e. Morquio Syndrome, 1 case) disease were studied as well. Each patient underwent preoperative radiological evaluation by means of X-Ray, CT scan and MRI of the craniocervical region. Occipitocervical instrumentation with a titanium U-shaped wired rod was performed in each patient. Autologous bone fusion was performed in all but the two cancer patients, in whom polymethylmetacrylate was used. Postoperatively, all the patients used an external orthosis for 3–6 months. Post-operative X-Ray, CT and MRI were performed on each patient. The Frankel clinical scale was used to asses the outcome at follow-up which ranged from 1 to 10 years. At maximum follow up, there was either clinical improvement or stabilization recorded in all but one patient. This patient with basilar impression transiently worsened from grade D to C and a spinal cord lesion was already evident before the operation on MRI examination.  Interpretation: The effectiveness of surgical management of craniovertebral junction instability by instrumentation and fusion was demonstratedly in our experience. Nevertheless, the choice of the surgical technique should be made with caution when a spinal cord lesion is revealed by preoperative neuroimaging studies. Published online April 28, 2003 Acknowledgments  We thank MS. Ciara Harraher for editorial assistance.  Correspondence: Visocchi Massimiliano MD, Institute of Neurosurgery, Catholic University of “Sacred Heart”, Lgo. A. Gemelli, 8, 00168 Rome, Italy.     

Functional MRI and 18F FDG-positron emission tomography for presurgical planning: comparison with electrical cortical stimulation

Summary.  Background: In patients with mass lesions near “eloquent” cortical areas different preoperative mapping techniques can be used. Two of the most widely used approaches include positron emission tomography (PET) and functional MRI (fMRI). We employed both methods in the same patients undergoing presurgical evaluation and compared the results to those obtained by direct electrical cortical stimulation (DECS).  Method: 22 patients with tumours of different aetiology near the central region were investigated. FMRI was performed using a T2^*-weighted gradient-echo BOLD sequence at 1.5 T, PET was performed after injection of 122–301 MBq ¹⁸F-Fluorodeoxyglucose (18-FDG) under rest and activation conditions. DECS was performed in all patients with recordings of muscles primarily involved in the investigated tasks.  Findings: In 19 patients all three modalities could be compared, 1 patient demonstrated discordance between fMRI and PET with DECS speaking in favour of fMRI, 6 patients had neighbouring results of PET and fMRI (between 1–2 cm distance), 12 patients had overlapping results.  Interpretation: The high incidence of neighbouring results is presumably related to fMRI specific artefacts. Advantages of fMRI are: Higher spatial and temporal resolution, more and different functional runs, shorter examination time, wider availability, longitudinal examinations, non-invasiveness and cost-effectiveness, easy registration to anatomical images. Advantages of PET are: higher signal-to-noise ratio, lesser susceptibility to artefacts (motion, draining veins), evaluation of tumour metabolism. It is our opinion that the neurosurgeon has to decide on a case-by-case basis which study suits his specific needs in the presurgical evaluation of his patient. Published online September 2, 2002 Acknowledgments  This study was supported by a grant from the German research council (Deutsche Forschungsgemeinschaft – DFG) (KR 2008 2/1). Correspondence: Timo Krings M.D., Department of Neuroradiology, University Hospital of the Technical University Aachen, Pauwelsstrasse 30, 52057 Aachen, Germany.     

Proton Magnetic Resonance Chemical Shift Imaging (1H CSI)-Directed Stereotactic Biopsy

Summary  Introduction. To add metabolic information during stereotactic biopsy target selection, the authors adopted proton chemical shift imaging (¹H CSI)-directed stereotactic biopsy. Currently, proton single voxel spectroscopy (SVS) technique has been reported in stereotactic biopsy. We performed ¹H CSI in combination with a stereotactic headframe and selected targets according to local metabolic information, and evaluated the pathological results.  Patients and Method. The ¹H CSI-directed stereotactic biopsy was performed in four patients. ¹H CSI and conventional Gd-enhancement stereotactic MRI were performed simultaneously after the fitting of a stereotactic frame. After reconstructing the metabolic maps of N-acetylaspartate (NAA)/phosphocreatine (Cr), phosphocholine (Cho)/Cr, and Lactate/Cr ratios, focal areas of increased Cho/Cr ratio and Lac/Cr ratios were selected as target sites in the stereotactic MR images.  Result. ¹H CSI is possible with the stereotactic headframe in place. No difficulty was experienced performing ¹H CSI or making a diagnosis. Pathological samples taken from areas of increased Cho/Cr ratios and decreased NAA/Cr ratios provided information upon increased cellularity, mitoses and cellular atypism, and facilitated diagnosis. Pathological samples taken from areas of increased Lac/Cr ratio showed predominant feature of necrosis.  Conclusion. ¹H CSI was feasible with the stereotactic headframe in place. The final pathological results obtained were concordant with the local metabolic information from ¹H CSI. We believe that ¹H CSI-directed stereotatic biopsy has the potential to significantly improve the accuracy of stereotactic biopsy targeting.