Integrated pre- and intraoperative imaging in a patient with an arteriovenous malformation located in eloquent cortex.

INTRODUCTION: The use of integrated pre- and intraoperative imaging may be useful when resecting brain lesions in close proximity to eloquent areas, such as the primary motor cortex and language cortices. CASE REPORT: A 32-year-old woman with an arteriovenous malformation (AVM) located in the primary motor cortex underwent surgery using functional neuronavigation. Blood-oxygenation-level-dependent functional magnetic resonance imaging (BOLD fMRI) and diffusion tensor tractography (DTT) were used for preoperative mapping of primary motor areas and the corticospinal tracts, respectively. The BOLD fMRI activations and DTT tractograms were integrated into the neuronavigation system and visualized intraoperatively throughout the operation. Furthermore, stereoscopic visualizations of the angioarchitecture based on 3D MRI angiograms were used to rehearse the surgical approach to the feeder vessels. Finally, intraoperative ultrasound was used to locate and clip the feeding vessels. CONCLUSION: The AVM was carefully resected with the aid of the above-mentioned imaging techniques, and the intuitive usefulness of the techniques was further substantiated by the rewarding postoperative outcome.

Surgical resection of high-grade gliomas in eloquent regions guided by blood oxygenation level dependent functional magnetic resonance imaging, diffusion tensor tractography, and intraoperative navigated 3D ultrasound.

OBJECTIVE: The aims of this study of patients with high-grade gliomas in eloquent brain areas were 1) to assess the postoperative functional outcome, 2) to determine the extent of tumour resection in these difficult locations, 3) to evaluate the practical usefulness of navigated blood oxygenation level-dependent functional magnetic resonance imaging and diffusion tensor tractography. PATIENTS AND METHODS: 25 consecutive patients were included in the study. The patients' gross functional neurological status was determined using the 7-step modified Rankin scale. The extent of tumour resection was determined using pre- and postoperative T(1)-weighted or T(1)-weighted, contrast-enhanced MRI images. RESULTS: The average preoperative modified Rankin scale was 1.56+/-0.77, whereas the average postoperative modified Rankin scale was 1.08+/-1.29. There was a significant improvement in mean modified Rankin scale score after surgery. The mean percentage of residual tumour was calculated to 16+/-22% of the original tumour volume (median 8%). Blood oxygenation level-dependent functional magnetic resonance imaging and diffusion tensor tractography were performed in 23 and 18 patients, respectively. Blood oxygenation level-dependent functional magnetic resonance imaging and diffusion tensor tractography facilitated identification of probable functional regions in 91% and 94% of the respective investigations. CONCLUSION: We feel that the combination of blood oxygenation level-dependent functional magnetic resonance imaging, diffusion tensor tractography, and 3D ultrasound facilitated maximal tumour resection with minimal deficits. The method permits an image-based functional monitoring of the brain during surgery that may aid the preservation of motor and language function.

Clinical validation of vessel-based registration for correction of brain-shift.

In this paper, we have tested and validated a vessel-based registration technique for correction of brain-shift using retrospective clinical data from five patients: three patients with brain tumors, one patient with an aneurysm and one patient with an arteriovenous malformation. The algorithm uses vessel centerlines extracted from segmented pre-operative MRA data and intra-operative power Doppler ultrasound images to compute first a linear fit and then a thin-plate spline transform in order to achieve non-linear registration. The method was validated using (i) homologous landmarks identified in the original data, (ii) selected vessels, excluded from the fitting procedure and (iii) manually segmented, non-vascular structures. The tracking of homologous landmarks show that we are able to correct the deformation to within 1.25 mm, and the validation using excluded vessels and anatomical structures show an accuracy of 1mm. Pre-processing of the data can be completed in 30 s per dataset, and registrations can be performed in less than 30s. This makes the technique well suited for intra-operative use.

Functional neuronavigation combined with intra-operative 3D ultrasound: initial experiences during surgical resections close to eloquent brain areas and future directions in automatic brain shift compensation of preoperative data.

OBJECTIVE: The aims of this study were: 1) To develop protocols for, integration and assessment of the usefulness of high quality fMRI (functional magnetic resonance imaging) and DTI (diffusion tensor imaging) data in an ultrasound-based neuronavigation system. 2) To develop and demonstrate a co-registration method for automatic brain-shift correction of pre-operative MR data using intra-operative 3D ultrasound. METHODS: Twelve patients undergoing brain surgery were scanned to obtain structural and fMRI data before the operation. In six of these patients, DTI data was also obtained. The preoperative data was imported into a commercial ultrasound-based navigation system and used for surgical planning and guidance. Intra-operative ultrasound volumes were acquired when needed during surgery and the multimodal data was used for guidance and resection control. The use of the available image information during planning and surgery was recorded. An automatic voxel-based registration method between preoperative MRA and intra-operative 3D ultrasound angiography (Power Doppler) was developed and tested postoperatively. RESULTS: The study showed that it is possible to implement robust, high-quality protocols for fMRI and DTI and that the acquired data could be seamlessly integrated in an ultrasound-based neuronavigation system. Navigation based on fMRI data was found to be important for pre-operative planning in all twelve procedures. In five out of eleven cases the data was also found useful during the resection. DTI data was found to be useful for planning in all five cases where these data were imported into the navigation system. In two out of four cases DTI data was also considered important during the resection (in one case DTI data were acquired but not imported and in another case fMRI and DTI data could only be used for planning). Information regarding the location of important functional areas (fMRI) was more beneficial during the planning phase while DTI data was more helpful during the resection. Furthermore, the surgeon found it more user-friendly and efficient to interpret fMRI and DTI information when shown in a navigation system as compared to the traditional display on a light board or monitor. Updating MRI data for brain-shift using automatic co-registration of preoperative MRI with intra-operative ultrasound was feasible. CONCLUSION: In the present study we have demonstrated how both fMRI and DTI data can be acquired and integrated into a neuronavigation system for improved surgical planning and guidance. The surgeons reported that the integration of fMRI and DTI data in the navigation system represented valuable additional information presented in a user-friendly way and functional neuronavigation is now in routine use at our hospital. Furthermore, the present study showed that automatic ultrasound-based updates of important pre-operative MRI data are feasible and hence can be used to compensate for brain shift.

Quality of life after treatment for incidental, unruptured intracranial aneurysms.

BACKGROUND: Discovering an intracranial aneurysm may profoundly affect the patient's quality of life. Patients living with unruptured and untreated aneurysms often report symptoms of anxiety and depression. There are few trials studying the quality of life after treatment of unruptured intracranial aneurysms. We aimed to compare the quality of life and symptoms of anxiety or depression after endovascular coiling or open surgery clipping of unruptured intracranial aneurysms, in patients with no prior subarachnoid haemorrhage. METHOD: 73 living patients were included. 44 had undergone open surgery clipping and 31 had undergone endovascular coiling within the last 5.5 years. We registered a number of parameters from medical records and the patients' current quality of life was assessed by a questionnaire. 63 of 73 (86.3%) returned our questionnaire, which included the Norwegian version of SF-36 and the Hospital Anxiety and Depression Scale (HAD). FINDINGS: Many patients treated for unruptured intracranial aneurysms have a relatively low quality of life. The low scores indicate that the patients experience limitations in their ability to work or accomplish desired activities due to perceived physical or mental handicaps. There were no significant differences between the open surgery group and the endovascular group when comparing quality of life parameters after treatment. A subgroup analysis of patients with a favourable functional outcome also showed reduced quality of life without any differences in the two treatment groups. There were no signs of improvement in quality of life over time. CONCLUSION: Quality of life after treatment does not seem to be a strong argument for choosing one modality of treatment over the other in patients with unruptured intracranial aneurysms. There are no significant differences in the quality of life of patients successfully treated using endovascular technique and patients who underwent craniotomy and clipping. We speculate that the low quality of life scores are due to factors unrelated to the aneurysms. The scores possibly reflect characteristics of a patient group where incidental aneurysms are more frequently diagnosed while undergoing extensive imaging procedures due to unrelated symptoms.

Endoscopy guided by an intraoperative 3D ultrasound-based neuronavigation system.

OBJECTIVE: We have investigated the feasibility of using 3D ultrasound-based neuronavigation for guiding neuroendoscopy. METHODS: A neuronavigation system with an integrated ultrasound scanner was used for acquiring the 3D ultrasound image data. The endoscope with a tracking frame attached was calibrated to the navigation system. The endoscope was guided based on intraoperative 3D ultrasound data in 9 operations. In 5 of the operations, ultrasound angiography data were also obtained. Updated image data (e. g., more than one 3D ultrasound dataset) were obtained in 6 of the operations. RESULTS: We found that the image quality of 3D ultrasound was sufficient for image guidance of the endoscope. Planning of the entry point and trajectory as well as finding optimal sites for fenestration were successfully performed. Blood vessels were visualized by 3D ultrasound angiography. In one procedure of third ventriculostomy, the basilar artery was visualized. Updated image data were quickly obtained, and in two of the cases, a reduction of the size of cysts was demonstrated. CONCLUSIONS: 3D ultrasound gives accurate images of sufficiently high quality for image guidance of neuroendoscopy. Updated 3D ultrasound datasets can easily be acquired and may adjust for brain shift. Ultrasound angiography image data are also available with this technology and can visualize vessels of importance.

Intra-operative 3D ultrasound in neurosurgery.

In recent years there has been a considerable improvement in the quality of ultrasound (US) imaging. The integration of 3D US with neuronavigation technology has created an efficient and inexpensive tool for intra-operative imaging in neurosurgery. In this review we present the technological background and an overview of the wide range of different applications. The technology has so far mostly been applied to improve surgery of tumours in brain tissue, but it has also been found to be useful in other procedures such as operations for cavernous haemangiomas, skull base tumours, syringomyelia, medulla tumours, aneurysms, AVMs and endoscopy guidance.

Ability of navigated 3D ultrasound to delineate gliomas and metastases--comparison of image interpretations with histopathology.

BACKGROUND: The objective of the study was to test the ability of a 3D ultrasound (US) based intraoperative imaging and navigation system to delineate gliomas and metastases in a clinical setting. The 3D US data is displayed as reformatted 2D image slices. The quality of the displayed 3D data is affected both by the resolution of the acquired data and the reformatting process. In order to investigate whether or not 3D US could be used for reliable guidance in tumour surgery, a study was initiated to compare interpretations of imaged biopsy sites with histopathology. The system also enabled concomitant comparison of navigated preoperative MR with histopathology. METHOD: Eighty-five biopsies were sampled between 2-7 mm from the tumour border visible in the ultrasound images. Biopsies were collected from 28 operations (7 low-grade astrocytomas, 8 anaplastic astrocytomas, 7 glioblastomas and 6 metastases). Corresponding cross-sections of preoperative MR T1, MR T2 and intraoperative US were concomitantly displayed, steered by the biopsy forceps equipped with a positioning sensor. The surgeons' interpretation of the images at the electronically indicated biopsy sites were compared with the histopathology of the samples. FINDINGS: The ultrasound findings were in agreement with histopathology in 74% (n = 31) for low-grade astrocytomas, 83% (n = 18) for anaplastic astrocytomas, 77% (n = 26) for glioblastomas and 100% (n = 10) for metastases. Excluding irradiated patients, the results for glioblastomas improved to 80% concurrence (n = 20). As expected tumour cells were found in biopsies outside the US visible tumour border, especially in low-grade gliomas. Navigated 3D US have a significantly better agreement with histopathology than navigated MR T1 for low-grade astrocytomas. CONCLUSION: Reformatted images from 3D US volumes give a good delineation of metastases and the solid part of gliomas before starting the resection. Navigated 3D US is at least as reliable as navigated 3D MR to delineate gliomas and metastases.

Stereoscopic navigation-controlled display of preoperative MRI and intraoperative 3D ultrasound in planning and guidance of neurosurgery: new technology for minimally invasive image-guided surgery approaches.

OBJECTIVE: This paper demonstrates a method that brings together three essential technologies for surgery planning and guidance: neuronavigation systems, 3D visualization techniques and intraoperative 3D imaging technologies. We demonstrate the practical use of an in-house interactive stereoscopic visualization module that is integrated with a 3D ultrasound based neuronavigation system. MATERIALS AND METHODS: A stereoscopy volume visualization module has been integrated with a 3D ultrasound based neuronavigation system, which also can read preoperative MR and CT data. The various stereoscopic display modalities, such as "cut plane visualization" and "interactive stereoscopic tool guidance" are controlled by a pointer, a surgical tool or an ultrasound probe. Interactive stereoscopy was tested in clinical feasibility case studies for planning and guidance of surgery procedures. RESULTS: By orientating the stereoscopic projections in accordance to the position of the patient on the operating table, it is easier to interpret complex 3D anatomy and to directly take advantage of this 3D information for planning and surgical guidance. In the clinical case studies, we experienced that the probe-controlled cut plane visualization was promising during tumor resection. By combining 2D and 3D display, interpretation of both detailed and geometric information may be achieved simultaneously. The possibilities of interactively guiding tools in a stereoscopic scene seemed to be a promising functionality for use during vascular surgery, due to specific location of certain vessels. CONCLUSION: Interactive stereoscopic visualization improves perception and enhances the ability to understand complex 3D anatomy. The practical benefit of 3D display is increased considerably when integrated with surgical navigation systems, since the orientation of the stereoscopic projection corresponds to the orientation of the patient on the operating table. Stereoscopic visualizations work well on MR and CT images, although volume rendering techniques are especially suitable for intraoperative 3D ultrasound image data.

Warm and cold sensory thresholds in patients with unilateral sciatica: C fibers are more severely affected than A-delta fibers.

OBJECTIVES: In order to evaluate if nerve root compression or inflammation is the most important pathogenetic mechanism in lumbar radicular pain, we investigated unmyelinated C-fiber function (warm sensation) and myelinated A-delta fiber function (cold sensation) in patients with unilateral L5 or S1 sciatica. MATERIAL AND METHODS: Forty consecutive patients with clinical and radiological evidence of unilateral L5 (n = 29) or S1 (n = 11) sciatica were studied. The warm and cold sensory thresholds (Somedic thermotest, method of limits) were measured on the anterolateral leg (L5 dermatome) and on the calf (S1 dermatome) on both sides. RESULTS: Warm thresholds were significantly higher on the symptomatic side compared to the non-symptomatic side (8.4+/-3.0 vs 6.2+/-2.5 degrees C, P < 0.0005) in the affected dermatome. In a subgroup with confirmed disk herniation at surgery (32 of the 34 operated), significant differences between the symptomatic and the non-symptomatic side for the affected dermatome, were found for both warm (P < 0.0005) and cold (P = 0.003) thresholds. No threshold difference was seen in patients with disk herniations contained within the outer annulus fibrosis (n = 22) compared to those with non-contained herniations (n = 10). CONCLUSIONS: Patients with unilateral sciatica and L5 or S1 nerve root involvement had increased warm thresholds suggesting impaired C-fiber function. Cold thresholds were significantly elevated in a subgroup with operatively confirmed disk herniation. Because myelinated axons are affected more by compression than unmyelinated ones, our results suggest that nerve root inflammation is more important than compression per se in the generation of sciatic pain.

Interstitial chemotherapy with carmustine-loaded polymers for high-grade gliomas: a randomized double-blind study.

OBJECTIVE: To find out the effect of carmustine (bischloroethyl-nitrosourea) combined with a biodegradable polymer in the treatment of malignant (Grades III and IV) gliomas, applied locally, at the time of the primary operation. METHODS: Prospective, randomized double-blind study of an active treatment group versus a placebo group. Conducted at the Departments of Neurosurgery of the University Hospitals of Helsinki, Tampere, and Turku in Finland and Trondheim in Norway. The study consisted of 32 patients (16 in each treatment group) enrolled between March 23, 1992, and March 19, 1993. The study was planned to include 100 patients but had to be terminated prematurely, because the drug that was being used had become unobtainable. The main outcome measures included the survival times of patients after the operations and the application of an active drug or placebo. RESULTS: The median time from surgery to death was 58.1 weeks for the active treatment group versus 39.9 weeks for the placebo group (P = 0.012). For 27 patients with Grade IV tumors, the corresponding times were 39.9 weeks for the placebo group and 53.3 weeks for the active treatment group (P = 0.008). At the end of the study, six patients were still alive, five of whom belonged to the active treatment group. CONCLUSION: Carmustine applied locally in a biodegradable polymer at the time of primary operation, seems to have a favorable effect on the life span of patients with high-grade gliomas.

Incorporation of ultrasonic imaging in an optically coupled frameless stereotactic system.

Frameless stereotactic interactive tracking systems relate a point in the surgical field to a corresponding point on the patients MR or CT scans in multiple planes. A basic weakness with these systems is that they cannot compensate for movement of target points due to brain shift caused by CSF drainage or lesion removal. Real time images can be obtained using ultrasonic techniques but the poor quality and definition and the ill-defined scan plane make interpretation difficult and reduce the usefulness of this modality. The authors have combined these two modalities by mounting light emitting diodes (LEDs) on the ultrasonic probe, thus allowing a "virtual tip" to be developed in the centre of the ultrasonic beam, and tracked via an optically coupled frameless stereotactic system (Radionics, OTS). This has allowed a direct correlation between pre-operative MR and the per-operative ultrasonic images using reformatted MR images. Ultrasound images are obtained through a separate skull opening and the image plane is determined by the position of the virtual tip. The ultrasonic and MR images are presented side by side for visual comparison. Minimally invasive tumour resection or haematoma removal could be carried out under ultrasonic guidance with direct interactive relation to the preoperative MR scans. Alternatively interactive image directed surgical procedures can be up-dated in real time by dynamic ultrasonic images taken in clearly defined scan planes.

EGF-effects in vitro and in vivo on a carcinoma cell line rich in EGFR.

T-CAR1 is a human carcinoma cell line established from a brain metastasis. The tumour cells overexpress EGFR and contain an amplified EGFR gene. In vitro in the presence of 5% human serum the tumour cells grow as adherent cells in monolayer. Shortly after exposure to EGF a large number of tumour cells round up and detach, whereas some remain adherent. At the same time a redistribution of actin occurs. Cytochalazin B prevented this reaction, which indicates that actin is involved in the detachment of the tumour cells. The EGF-detached tumour cells however, did not differ from the tumour cells which remained adherent after EGF-exposure with regard to parameters such as growth in soft agar, growth response to EGF, tumour necrosis factor-alpha, interferon-gamma, and carmustin (BCNU), level of EGFR gene expression and EGFR gene amplification, S-phase fraction, and amount of DNA. It was speculated whether the EGF-induced cellular detachment in vitro could be correlated to metastatic potential in vivo or not. In order to address this issue, in vivo studies with subcutaneous T-CAR1 tumours in nude mice were performed. Administration of EGF resulted in growth stimulation in contrast to growth inhibition in vitro, whereas no effect of EGF on the metastatic potential was observed. Thus, the EGF-mediated tumour cell detachment seems to be restricted to in vitro conditions only.

C-erbB-2/HER-2 protein in human intracranial tumours.

Normal and neoplastic human intracranial tissues were examined by immunohistochemistry for c-erbB-2/HER-2 protein expression. Positive staining was observed in 1/41 gliomas, 1/2 medulloblastomas, 1/1 germinoma, 11/16 meningiomas, 1/3 anaplastic meningiomas and 11/19 metastatic brain carcinomas. No positive staining was observed in normal intracranial tissues. Thus, the expression of the c-erbB-2/HER-2 protein is limited to intracranial tumour tissues, principally meningiomas and metastatic carcinomas to the brain.

Epidermal growth-factor and transforming growth factor-alpha in human meningiomas.

Recently we have shown that human meningiomas overexpress epidermal growth factor receptor (EGFR) (Torp SH et al APMIS 100: 797-802, 1992). We therefore wanted to examine these tumours for the expression of the EGFR ligands epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha). Normal human meningeal tissues were used as controls. Immunohistochemistry (IH) and radioimmunoassay (RIA) demonstrated the presence of EGF and/or TGF-alpha. immunoreactivity in sixteen of nineteen meningiomas. By means of RIA detectable amount of TGF-alpha was also recorded in normal leptomeninges. Discrepancies between IH and RIA were noted and are discussed. Our findings suggest that EGFR/EGF/TGF-alpha play a role in growth regulatory mechanisms in human meningiomas.

Expression of epidermal growth factor receptor in human meningiomas and meningeal tissue.

The aim of this study was to examine meningeal tissue under normal, reactive, and neoplastic conditions for expression of epidermal growth factor receptor (EGFR) using an improved histochemical method, namely biotinylated epidermal growth factor. EGFR was found in all the examined meningiomas (12 benign and three anaplastic) and in neonatal rat meninges, whereas normal and injured adult human and rat meninges did not exhibit detectable EGFR. These observations indicate that EGFR is involved in the development of meningeal tissue. Further, EGFR is abnormally expressed in meningeal tumours, indicating a role of EGFR in the neoplastic process of these tumours. The regular expression of EGFR in human meningiomas suggests EGFR as a tumour marker for this tumour type.

Expression of the epidermal growth factor receptor gene in human brain metastases.

Biopsy specimens of human brain metastases were examined for amplification and expression of the proto-oncogene c-erbB1 (located on chromosome 7) encoding the epidermal growth factor receptor (EGFR). Moreover, the tumour DNA was also examined for amplification of other cancer-related genes on this chromosome: the proto-oncogene c-met, the gene for platelet-derived growth factor A-chain, and the gene for plasminogen activator inhibitory type 1. All 18 brain metastases demonstrated positive binding of biotinylated EGF on cryosections. Three out of 18 metastases had amplification of the EGFR gene; the other chromosome-7 genes tested were not amplified. Thus, an increased EGFR gene expression seems to be a general finding in a wide range of carcinomas metastatic to the brain, whereas we found only occasional selective EGFR gene amplifications in single cases.

Relationships between Ki-67 labelling index, amplification of the epidermal growth factor receptor gene, and prognosis in human glioblastomas.

The aim of this study was to determine possible relationships between Ki-67 labelling index (Ki-67 LI), amplification of the epidermal growth factor receptor (EGFR) gene, and prognosis in human glioblastomas. Ki-67 LI was determined on cryosections of biopsy specimens of 20 human glioblastomas with a mouse anti-human Ki-67 monoclonal antibody. Amplification of the EGFR gene was determined by slot blot and Southern blot analyses of DNA extracted from the tumour biopsies. The Ki-67 LI was higher in the glioblastoma group with EGFR gene amplification (8 tumours, median value of Ki-67 LI 4.2, range 0.4-24.6) than in those without EGFR gene amplification (12 tumours, median value of Ki-67 LI 0.8, range 0.2-11.8) (0.05 p less than 0.1). The glioblastoma patients with Ki-67 LI greater than 1.5 (10 tumours) had a statistically significant shorter survival than those with Ki-67 LI less than 1.5 (10 tumours) (p less than 0.05). The glioblastoma patients with EGFR gene amplification lived shorter time than those without EGFR gene amplification (p greater than 0.05).

Amplification of the epidermal growth factor receptor gene in human gliomas.

Biopsy specimens of 19 human gliomas (10 glioblastomas, 2 anaplastic astrocytomas, 4 astrocytomas, one mixed glioma, one oligodendroglioma and one ependymoma) were examined for amplification of tumour-related genes located on chromosome 7: the proto-oncogene c-erb-B1 (encoding the epidermal growth factor receptor (EGFR], the proto-oncogene c-met, the platelet-derived growth factor A-chain gene, and the plasminogen activator inhibitor type-1 gene. Gene amplification was observed in 6 glioblastomas, and the EGFR gene was the only chromosome-7-gene examined that was amplified. The selective EGFR gene amplification in human glioblastomas suggests its potential role in the progression of some of these tumours.

Epidermal growth factor receptor expression in human gliomas.

The expression of epidermal growth factor receptor (EGFR) was determined in cryosections of 42 human gliomas using biotinylated epidermal growth factor (B-EGF) and two monoclonal antibodies (mAb) against EGFR. All gliomas were found to express EGFR when examined with B-EGF, whereas 33 expressed EGFR when examined with the two mAbs. The highly malignant gliomas (glioblastomas and anaplastic astrocytomas) had a more heterogeneous staining strongly with B-EGF than did the low-grade gliomas (astrocytomas, oligodendrogliomas, mixed gliomas, and ependymomas). This indicates that high-grade gliomas contain more tumour cells rich in EGFR than do the low-grade gliomas. Reactive astrocytes, ependymal cells, and many types of nerve cells (cerebral cortical pyramidal cells, pyramidal and granular hippocampal cells, Purkinje cells, cerebellar granular cells and neurons in the molecular layer of the cerebellum) expressed EGFR, whereas small neurons and normal glial cells were not found to express EGFR.