Functional imaging: where do we go from here?

As highly invasive and infiltrative tumors, gliomas are hard to delineate from healthy brain parenchyma, even with the microscope enhanced eye of an experienced neurosurgeon. However, the surgical goal remains maximum extent of tumor volume resection with a preservation of neurological function. With functional data integrated and visualized in the navigation system, postoperative morbidity can be reduced. With the so far well established techniques diffusion-tensor-imaging (DTI) based fiber tractography and functional MRI (fMRI), white matter tracts or eloquent cortical areas can be displayed. With magnetic resonance spectroscopy (MRS) and also positron emmission computed tomography (PET), methods displaying brain metabolism are also widely used. However, further technical and computational development of these methods has already shown extended insights in brain networks and pathologies and promises further reduction of postoperative morbidity, while used in navigation systems. In addition to these methods, novel techniques have already been implemented and successfully used in the clinical routine. In this way, this review summarizes recent developments in DTI, fMRI, MRSI and PET, also with their use during neurosurgical operations, but also gives introduction in novel methods like navigated transcranial magnetic stimulation (nTMS) or advanced diffusion models as base for fiber tracking.

Operative treatment of prolactinomas: indications and results in a current consecutive series of 212 patients.

OBJECTIVE: Medical therapy with dopamine agonists (DA) is the primary treatment of choice in most patients with prolactinomas. 'Classical' surgical indications are intolerance or lack of efficiency of DA therapy. Focusing on a possible shift of recent indications, we retrospectively analyzed our results of surgical treatment in prolactinomas. PATIENTS AND METHODS: Between 1990 and 2005, we have operated on 212 consecutive patients with prolactinomas. Surgical indications were divided into 'classical' indications and 'modern' indications defined as cystic prolactinomas or patients with microprolactinomas who individually decided on a primary surgical treatment. RESULTS: Initial overall remission was accomplished in 53.2% including giant prolactinomas. However, in microadenomas, the remission rate was significantly higher with 91.3%. Overall remission at the latest follow-up was 42.7%, but 72.5% in intrasellar tumors, 80% in cystic prolactinomas, and 84.8% in microprolactinomas. The overall recurrence rate was 18.7%. Relapse of hyperprolactinemia in microprolactinomas was 7.1%. In our series, continually less patients were surgically treated for 'classical' indications. By contrast, the number of patients who individually decided on a primary surgical therapy has increased considerably. CONCLUSION: Remission rates after surgical treatment of prolactinomas remain excellent, particularly in microadenoma and intrasellar macroadenomas, whereas morbidity of transsphenoidal surgery is low in the hands of experienced pituitary surgeons. Our remission rates not only confirm the already interdisciplinarily accepted surgical indications, but also emphasize the value of primary transsphenoidal surgery as a discussion-worthy alternative to dopaminergic therapy in young patients with microprolactinomas or cystic tumors.

Correction of susceptibility artifacts in diffusion tensor data using non-linear registration.

Diffusion tensor imaging can be used to localize major white matter tracts within the human brain. For surgery of tumors near eloquent brain areas such as the pyramidal tract this information is of importance to achieve an optimal resection while avoiding post-operative neurological deficits. However, due to the small bandwidth of echo planar imaging, diffusion tensor images suffer from susceptibility artifacts resulting in positional shifts and distortion. As a consequence, the fiber tracts computed from echo planar imaging data are spatially distorted. We present an approach based on non-linear registration using Bézier functions to efficiently correct distortions due to susceptibility artifacts. The approach makes extensive use of graphics hardware to accelerate the non-linear registration procedure. An improvement presented in this paper is a more robust and efficient optimization strategy based on simultaneous perturbation stochastic approximation (SPSA). Since the accuracy of non-linear registration is crucial for the value of the presented correction method, two techniques were applied in order to prove the quality of the proposed framework. First, the registration accuracy was evaluated by recovering a known transformation with non-linear registration. Second, landmark-based evaluation of the registration method for anatomical and diffusion tensor data was performed. The registration was then applied to patients with lesions adjacent to the pyramidal tract in order to compensate for susceptibility artifacts. The effect of the correction on the pyramidal tract was then quantified by measuring the position of the tract before and after registration. As a result, the distortions observed in phase encoding direction were most prominent at the cortex and the brainstem. The presented approach allows correcting fiber tract distortions which is an important prerequisite when tractography data are integrated into a stereotactic setup for intra-operative guidance.

Diffusion tensor imaging and white matter tractography in patients with brainstem lesions.

BACKGROUND: Diffusion tensor imaging (DTI) and white matter tractography (WMT) are promising techniques for estimating the course, extent, and connectivity patterns of the white matter (WM) structures in the human brain. In this study, we investigated the ability of DTI and WMT to visualize white matter tract involvement for the preoperative surgical planning and postoperative assessment of brainstem lesions. METHODS: Preoperative and postoperative DTI data (echo-planar, 1.5T) were retrospectively analyzed in 10 patients with brainstem lesions (3 diffuse, 7 focal). WMT applying a tensor deflection algorithm was used to reconstruct WM tracts adjacent to the lesions. Reconstructed tracts included corticospinal tracts and medial lemnisci. The clinical and imaging follow-up data were also compared and analyzed. FINDINGS: WMT revealed a series of tract alteration patterns including deviation, deformation, infiltration, and apparent tract interruption. WMT reconstructions showed that the major WM tracts were preserved during surgery and improved in position and appearance postoperatively. These findings correlated with the improvement or preservation of neurological function as determined by clinical assessment. CONCLUSIONS: Compared with the information provided by conventional MR imaging, DTI and WMT provided superior quantification and visualization of lesion involvement in eloquent fibre tracts of the brainstem. Moreover, DTI and WMT were found to be beneficial for white matter recognition in the neurosurgical planning and postoperative assessment of brainstem lesions.

Multimodal coregistration in patients with temporal lobe epilepsy--results of different imaging modalities in lateralization of the affected hemisphere in MR imaging positive and negative subgroups.

BACKGROUND AND PURPOSE: In this study, intensive video electroencephalogram (EEG) monitoring, high-resolution MR imaging (MR imaging), proton MR spectroscopy ((1)H-MR spectroscopy) and single-photon emission CT (SPECT) were compared in patients with temporal lobe epilepsy (TLE) to evaluate lateralization of affected hemisphere with regard to bilateral affection and postoperative outcome. PATIENTS AND METHODS: Recall ratio of each technique for indicating the affected hemisphere was determined in 49 patients with TLE. Postoperative outcome was established by Engel classification. RESULTS: Twenty-two of 25 patients with TLE with evidence for hippocampal sclerosis in MR imaging (MR imaging-positive) were graded as unilateral by EEG findings whereas 3 were classified as bilateral. Fourteen of 24 MR imaging-negative patients were graded as unilateral by EEG and 10 as bitemporal. (1)H-MR spectroscopy indicated concordant lateralization to EEG in 82% of MR imaging-positive patients and 71% of MR imaging-negative patients and to SPECT in 84% of MR imaging-positive patients and 67% of MR imaging-negative patients with TLE. In unilateral TLE, the concordance rate of both modalities was 74% in MR imaging-positive patients and 67% in MR imaging-negative patients. Contralateral findings to EEG focus were found in 28% by (1)H-MR spectroscopy and in 27% by SPECT. Concordant findings to the operated side of different modalities revealed a clear tendency (P = .08) for a better postoperative outcome compared with bitemporal or contralateral findings. CONCLUSION: Our data demonstrate that multimodal imaging in patients with TLE improves lateralization of affected hemispheres, especially in patients without pathologic findings in MR imaging, and indicates bilateral effect, which is important to identify patients who will benefit from surgery.

Changes in fiber integrity, diffusivity, and metabolism of the pyramidal tract adjacent to gliomas: a quantitative diffusion tensor fiber tracking and MR spectroscopic imaging study.

BACKGROUND AND PURPOSE: The underlying changes in the neuronal connectivity adjacent to brain tumors cannot always be depicted by conventional MR imaging. The hypothesis of this study was that preoperative sensorimotor deficits are associated with impairment in pyramidal fiber bundles. Hence, we investigated the potential of combined quantitative diffusion tensor (DT) fiber tracking and MR spectroscopic imaging (MRSI) to determine changes in the pyramidal tract adjacent to gliomas. MATERIALS AND METHODS: Quantitative DT fiber tracking and proton MRSI were performed in 20 patients with gliomas with WHO grades II-IV. Eight patients experienced preoperative sensorimotor deficits. Mean diffusivity (MD), fractional anisotropy (FA), and number of fibers per voxel (FpV) were calculated for the pyramidal tract of the ipsilateral and contralateral hemisphere. Metabolite concentrations for choline-containing compounds (Cho), creatine (Cr), and N-acetylaspartate (NAA) were computed, using LCModel, for all voxels located at the pyramidal tracts. RESULTS: For the whole pyramidal tract, quantitative DT fiber tracking resulted in significantly lower FpV and FA values (P < .001), but not MD values, for the ipsilateral hemisphere. For the section of the fiber bundle closest to the lesion, we found significantly decreased FpV and FA (P < .001) and increased MD (P = .002). MRSI showed, for the same volumes of interest, significantly decreased NAA (P = .001), increased Cho (P = .034) and Cho/NAA (P = .001) for the ipsilateral pyramidal tract. In patients suffering sensorimotor deficits, we found significantly lower FA (P = .022) and higher MD values (P = .026) and a strongly negative correlation between FA and MD (R = -0.710, P = .024) but no correlation in patients without deficits (R = 0.078, ns). CONCLUSION: Quantitative DTI was able to show significant differences in diffusivity of the pyramidal tract in patients with sensorimotor deficits in relation to patients without them. The additional use of proton MRSI may be helpful to discern whether these diffusivity changes in fiber tracts are caused by tumor infiltration or peritumoral edema.

Periventricular nodular heterotopia: A challenge for epilepsy surgery.

Pharmacoresistant focal epilepsies due to periventricular nodular heterotopia are a diagnostic and therapeutic challenge because of the need of invasive presurgical diagnostics and the selection of an optimal surgical approach. Invasive investigations in previous studies showed that focal epileptic activity can be correlated predominantly either with one of the nodular heterotopia or with neocortical epileptogenic zones distant to the periventricular nodules. Up to now, invasive recordings were required for localization of epileptic activity and its correlation to heterotopia. The following case presentation reports on a non-invasive approach using magnetic source imaging (MSI) combined with intraoperative ECoG. MSI combines preoperative data from magnetic resonance imaging (MRI) with magnetoencephalography (MEG). The MSI data for definition of the localization of the epileptic activity and functional important areas were coregistered with the intraoperative high-field-MRI and diffusion tensor imaging-based fiber tracking (DTI) of the visual pathway using a neuronavigational system. A neuronavigation-guided surgical resection of the epileptogenic area was performed leaving the heterotopia and the visual tract fibers intact. Postoperatively preservation of the visual fields was documented and the frequency of seizures was markedly reduced.

Alveolar rhabdomyosarcoma of the clivus with intrasellar expansion: Case report.

Rhabdomyosarcomas are common tumors of the head and neck region in children. However, a primarily intracranial localization of this tumor entity is rare. We report on a 3-year-old boy presenting with double vision due to left VI (th) nerve palsy. No other neurological deficits were recognized by clinical inspection. MRI scans visualized an enhancing mass lesion in the upper clivus compressing the cavernous sinus and the pituitary gland. Transsphenoidal biopsy was performed and histopathological examination as well as molecular diagnostics confirmed the diagnosis of an alveolar rhabdomyosarcoma (ARMS). Staging identified a metastatic lesion in the fourth thoracic vertebra resulting in the diagnosis of stage IV disease. Treatment modality included stereotactic radio- and chemotherapy.

Uncertainty in diffusion tensor based fibre tracking.

BACKGROUND: Diffusion tensor imaging and related fibre tracking techniques have the potential to identify major white matter tracts afflicted by an individual pathology or tracts at risk for a given surgical approach. However, the reliability of these techniques is known to be limited by image distortions, image noise, low spatial resolution, and the problem of identifying crossing fibres. This paper intends to bridge the gap between the requirements of neurosurgical applications and basic research on fibre tracking uncertainty. METHOD: We acquired echo planar diffusion tensor data from both 1.5 T and 3.0 T scanners. For fibre tracking, an extended deflection-based algorithm is employed with enhanced robustness to impaired fibre integrity such as caused by diffuse or infiltrating pathological processes. Moreover, we present a method to assess and visualize the uncertainty of fibre reconstructions based on variational complex Gaussian noise, which provides an alternative to the bootstrap method. We compare fibre tracking results with and without variational noise as well as with artificially decreased image resolution and signal-to-noise. FINDINGS: Using our fibre tracking technique, we found a high robustness to decreased image resolution and signal-to-noise. Still, the effects of image quality on the tracking result will depend on the employed fibre tracking algorithm and must be handled with care, especially when being used for neurosurgical planning or resection guidance. An advantage of the variational noise approach over the bootstrap technique is that it is applicable to any given set of diffusion tensor images. CONCLUSIONS: We conclude that the presented approach allows for investigating the uncertainty of diffusion tensor imaging based fibre tracking and might offer a perspective to overcome the problem of size underestimation observed by existing techniques.

Intraoperative high-field MRI: anatomical and functional imaging.

Intraoperative high-field magnetic resonance (MR) imaging with integrated microscope-based navigation is at present one of the most sophisticated technical methods providing a reliable immediate intraoperative quality control. It enables intraoperative imaging at high quality that is up to the standard of up to date pre- and postoperative neuroradiological routine diagnostics. The major indications are pituitary tumor surgery and glioma surgery. In pituitary tumor surgery intraoperative MRI helps to localize hidden tumor remnants that would be otherwise overlooked. The same is true for glioma surgery, where the optimal extent of resection by simultaneous preservation of functional integrity can be achieved. This is possible since high-field MR imaging offers various modalities beyond standard anatomical imaging, such as MR spectroscopy, diffusion tensor imaging, and functional MR imaging which may also be applied intraoperatively, providing not only data on the extent of resection and localization of tumor remnants but also on metabolic changes, tumor invasion, and localization of functional eloquent cortical and deep-seated brain areas.

Visualization of the pyramidal tract in glioma surgery by integrating diffusion tensor imaging in functional neuronavigation.

OBJECT: The aim of this study was to investigate whether diffusion tensor imaging (DTI) can be integrated into functional navigation for the intraoperative visualization of the pyramidal tract. METHODS: A single-shot spin-echo diffusion-weighted echo planar imaging sequence on a 1.5 T magnetic resonance (MR) scanner was used for DTI. One null image and six diffusion-weighted images (high B value 1 000 mm/s (2)) were obtained. Color-encoded fractional anisotropy maps of the principal eigenvector rendered as a boxoid within each voxel were used for segmentation of the pyramidal tract. The segmented images were rigidly registered with a T(1)-weighted gradient echo 3D dataset for navigation in 16 patients with gliomas. In tumors adjacent to the motor cortex (n = 6) data from functional MR imaging were co-registered. RESULTS: The whole DTI processing lasted about 25-30 minutes in each case. In all cases DTI could be integrated into the navigational dataset resulting in an intraoperative visualization of the pyramidal tract by microscope-based navigation. Navigational accuracy measured as the target registration error was 1.2 +/- 0.46 mm. Registration of fractional anisotropy maps with the 3D navigational dataset was possible with an error of less than 2 mm. Co-registration with fMRI was consistent with DTI data. A neurological deterioration was observed only in one patient. CONCLUSIONS: DTI can be reliably integrated into navigational datasets. Thus, microscope-based neuronavigation can be used for an intraoperative visualization of the course of the pyramidal tract. However, a possible shifting of the pyramidal tract has to be taken into account after major tumor parts are removed.

An automated robotic approach with redundant navigation for minimal invasive extended transsphenoidal skull base surgery.

BACKGROUND: The aim of this work was to determine the feasibility of a robotic-assisted and fully automated approach to the sphenoid sinus. An image-guided robotic system was designed to address potential human errors in performing transsphenoidal sinus surgery by combining the reproducible accuracy of a robotic system with standard computer navigation. METHODS: A six-degrees of freedom robotic assistance system and an opto-electrical navigation system were combined for image-guided assistance with redundantly controlled robotics. Newly designed endoscopic instruments for robotic surgery have been developed and are described. Telemanipulatory, as well as fully automated procedures, were tested on cadaveric heads as part of a preclinical trial. RESULTS: A fully automated sphenoidotomy as well as a telemanipulatory sphenoidectomy were performed successfully on cadaveric heads. Intraoperative performance, accuracy assessment studies, as well as possible sources of stereotactic offsets are described. The mean measured robotic reproducibility accuracy was 0.056 mm (range: 0.02 - 0.14 mm) and the mean overall navigated robotic accuracy, including all transformation and registration errors was 1.53 mm (range: 1.13 - 1.89 mm) respectively. CONCLUSION: A system for robot-guided surgery in combination with redundant navigational control was developed. It allows highly accurate maneuvers, performed either in a telemanipulation mode as master-slave system or in a fully automated fashion. A sphenoidectomy on cadaveric heads was performed in both telemanipulation and fully automated modes. The overall intraoperative accuracy was in the range of the resolution of the CT images and stereotactic offsets were caused mainly due to deflections of the endoscopic operating instrument.

[Development of an active robot system for multi-modal paranasal sinus surgery]. / Entwicklung eines aktiven Robotersystems für die multimodale Chirurgie der Nasennebenhöhlen.

BACKGROUND: Severe complications in endoscopic paranasal sinus surgery are rare, however, when they occur they are often fatal. Injuries to the optic nerve or the internal carotid artery mostly occur after penetration of the sphenoid sinus' anterior wall. METHODS: We present the robot system "A 73" with its newly designed 4-canal-microendoscope and special instruments that meets the demands of endoscopic paranasal sinus surgery. A fully automated perforation of the sphenoid sinus' anterior wall was performed in five cadaveric specimens. RESULTS: The sphenoid sinus' anterior wall could be perforated without damaging the surrounding structures in all cases. Subsequently, the approach was enlarged to the desired diameter using telemanipulation mode. The analysis of both the transformation error and intraopertive accuracy showed values in the submillimeter range. CONCLUSIONS: Using a newly developed robotic system, a fully automated perforation of the sphenoid sinus' anterior wall was performed precisely and reproducibly. This approach can be enlarged in a telemanipulation mode.

Determination of the elasticity parameters of brain tissue with combined simulation and registration.

Reliable elasticity parameters describing the behavior of a given material are an important issue in the context of physically-based simulation. In this paper we introduce a method for the determination of the mechanical properties of brain tissue. Elasticity parameters Young's modulus E and Poisson's ratio nu are estimated in an iterative framework coupling a finite element simulation with image registration. Within this framework, the outcome of the simulation is parameterized with both elasticity moduli that are automatically varied until optimal image correspondence between the simulated and the intraoperative data is achieved. We calculated optimal mechanical properties of brain tissue in six cases. The statistical analysis of the obtained values showed a good correlation of the results, thus proving the value of the method. An approach combining simulation and registration for the determination of the mechanical brain tissue properties is presented. This contributes to performing reliable physically-based simulation of soft tissue movement.

Magnetic source imaging supports clinical decision making in glioma patients.

OBJECTIVE: This study addresses the potential utility of preoperative functional imaging with magnetoencephalography (MEG) for the selection of glioma patients who are likely to benefit from resective surgical treatment regarding postoperative morbidity. METHODS: One hundred and nineteen patients with gliomas adjacent to sensorimotor, visual and speech related brain areas were investigated preoperatively with a MAGNES II biomagnetometer. In each patient the pre-surgical evaluation was focussed on the visual, sensorimotor cortex and/or of the speech related brain areas. A grading system was then used according to the distance of the MEG activation sources to the nearest tumour border to determine the further treatment. The therapeutic options consisted in conservative treatment, stereotactic biopsy and/or a radiation and chemotherapy, substantial cytoreduction and the gross total removal of the lesion. RESULTS: From 119 investigated patients, 55 patients (46.2%) were not considered for surgery due to tumour invasion to functional cortex. Sixty four patients (53.8%) were chosen for resective surgery. In the surgical group only four patients (6.2%) suffered from neurological deterioration. CONCLUSIONS: Magnetic source imaging (MSI) proved to be a valuable help in the clinical decision making process of lesions adjacent to functional important brain areas. The relative high number of patients in whom MSI warns of the postoperative crippling sequelae may lead to a better selection of patients who benefit from resective surgery. This method may help to find the patients for whom conservative treatment seems to be more favourable concerning quality of life in the surviving time.

Functional neuronavigation and intraoperative MRI.

Our concept of computer assisted surgery is based on the combination of intraoperative magnetic resonance (MR) imaging with microscope-based neuronavigation, providing anatomical and functional guidance simultaneously. Intraoperative imaging evaluates the extent of a resection, while the additional use of functional neuronavigation, which displays the position of eloquent brain areas in the operative field, prevents increasing neurological deficits, which would otherwise result from extended resections. Up to mid 2001 we performed intraoperative MR imaging using a low-field 0.2 Tesla scanner in 330 patients. The main indications were the evaluation of the extent of resection in gliomas, pituitary tumours, and in epilepsy surgery. Intraoperative MR imaging proved to serve as intraoperative quality control with the possibility of an immediate modification of the surgical strategy, i.e. extension of the resection. Integrated use of functional neuronavigation prevented increased neurological deficits. Compared to routine pre- or postoperative imaging being performed with high-Tesla machines, intraoperative image quality and sequence spectrum could not compete. This led to the development of the concept to adapt a high-field MR scanner to the operating environment, preserving the benefits of using standard microsurgical equipment and microscope-based neuronavigational guidance with integrated functional data, which was successfully implemented by April 2002. Up to the end of 2002, 95 patients were investigated with the new setup. Improved image quality, intraoperative workflow, as well as enhanced sophisticated intraoperative imaging possibilities are the major benefits of the high-field setup.

Frameless stereotactic brain biopsy procedures using the Stealth Station: indications, accuracy and results.

This study presents the results of 57 stereotactic brain biopsies using a frameless neuronavigation system, the Stealth Station. The supratentorial lesions had a mean diameter of 33 mm and a mean distance of 32 mm from the entry point at brain surface. In all cases the stereotactic procedure was planned in the preoperative 3-D magnetic resonance data set. In seven cases additional data for identification of eloquent brain areas was integrated from magnetoencephalography or functional magnetic resonance imaging. During surgery the samples were sent to neuropathological examination and the operation completed after the confirmation of pathological tissue. Using this method, in 56 cases a pathological tissue was obtained and a diagnostic yield of 98% was achieved. In two cases (3.5%) a new neurological deficit remained (hemiparesis and visual field deficit). The mean operation time was 92 minutes including examination of frozen sections. The results of our series demonstrate, that frameless stereotactic systems can also be reliably applied for biopsy of supratentorial lesions larger than 15 mm. Frameless stereotaxy in combination with intraoperative pathological confirmation is a safe and reliable method for stereotactic brain biopsy with a diagnostic yield comparable to frame-based stereotaxy.

Preliminary experience in glioma surgery with intraoperative high-field MRI.

OBJECTIVE: To apply a new setup, combining the benefits of high-field magnetic resonance imaging (MRI) with microscope-based neuronavigation, providing anatomical and functional guidance, in glioma surgery. MATERIAL AND METHODS: MR imaging was performed using a 1.5 T scanner, located in a radiofrequency-shielded operating theatre. The patient is lying on a rotating operating table, which is locked at the 160 degree position for surgery at the 5 G zone and turned into the scanner for imaging. The microscope, placed in the 5 G zone, in combination with a ceiling mounted navigation system enables microscope-based neuronavigation; integrated data from magnetoencephalography and functional MRI provide functional guidance. RESULTS: 126 patients were investigated with intraoperative high-field MRI, among them were 37 patients with gliomas. In the biopsy/catheter group (n = 8) MRI reliably depicted the needle position or the location of catheter placement. In the group with glioma resection (n = 29) intraoperative MRI revealed that the surgical objective was not achieved in 28%, leading to further tumour removal. We did not observe complications attributable to intraoperative high-field MRI. Image quality was not diminished by the operating room equipment, so that there was nearly no noticeable difference between pre- and intraoperative image quality. Neuronavigational guidance was applied in 31 patients: the integrated use of functional data prevented an increased morbidity despite extended resections. CONCLUSION: Intraoperative high-field MRI allows a reliable delineation of the extent of resection in glioma surgery. If the surgical objective was not met, a modification of the surgical strategy during the same operation is possible, thus leading to more radical resections. Furthermore, high-field MRI offers increased image quality and a much broader spectrum of different imaging modalities, compared to previous intraoperative low-field systems.