Nanoscaled ultrasound contrast agents for enhanced sonothrombolysis.

Sonothrombolysis, the enhancement of thrombolysis with ultrasound (US), is widely used in clinical practice. The use of an ultrasound contrast agent can lead to a further reduced recanalization time of the occluded blood vessel and thus to better outcome for the patient. In this study the sonothrombolytic efficacy of our new nanoscaled ultrasound contrast agent (NUSCA) was investigated. This new contrast agent has a size of less than 100 nm and should thus be able to penetrate the thrombus and achieve a thrombolysis from inside out. In this study human whole blood clots were exposed to US, US and NUSCA, US and recombinant tissue plasminogen activator (rt-Pa) or urokinase (UK), or a combination of US, NUSCA and thrombolytic drug in a closed-loop flow model. We sonicated with diagnostic US at a frequency of 2.85 MHz for 30 min. Clot mass loss of 50.6 ± 6.0% for the combination of US, NUSCA and rt-PA was found. Using UK as thrombolytic drug 57.7 ± 9.0% clot mass loss could be seen. Thus the weight loss exceeded the conventional values of up to 30%. Scanning electron microscopy (SEM) images revealed changes of the fibrin network on the thrombus surface. The NUSCA was able to loosen the network and induce large pores in the thrombus surface. The high rates of clot mass loss and the obvious changings of fibrin structure make our NUSCA a promising tool for sonothrombolytic therapy.

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.

[Transcranial magnetic stimulation and motor cortex stimulation in neuropathic pain]. / Transkranielle Magnetstimulation und Motorkortexstimulation bei neuropathischen Schmerzen.

Non-invasive and invasive cortical stimulation allows the modulation of therapy-refractory neuropathic pain. High-frequency repetitive transcranial magnetic stimulation (rTMS) of the contralateral motor cortex yields therapeutic effects at short-term and predicts the benefits of epidural motor cortex stimulation (MCS). The present article summarizes the findings on application, mechanisms and therapeutic effects of cortical stimulation in neuropathic pain.

The MRI volumetry of the posterior fossa and its substructures in trigeminal neuralgia: a validated study.

PURPOSE: Our aim was to determine whether the anatomical configuration of the posterior fossa and its substructures might represent a predisposition factor for the occurrence of clinical neurovascular conflict in trigeminal neuralgia (TN). METHODS: We used MRI volumetry in 18 patients with TN and 15 controls. The volume of the pontomesencephalic cistern, Meckel's cave and the trigeminal nerve on the clinical and non-affected sides was compared. The reliability has been assessed in all measurements. RESULTS: The posterior fossa volume was not different in the clinical and control groups; there was no difference between the affected and non-affected sides when measuring the pontomesencephalic cistern and Meckel's cave volume either. The volume of the clinically affected trigeminal nerve was significantly reduced, but with a higher error of measurement. CONCLUSIONS: We did not find any association between the clinical neurovascular conflict (NVC) and the size of the posterior fossa and its substructures. MRI volumetry may show the atrophy of the affected trigeminal nerve in clinical NVC.

[Treatment of intraventricular hemorrhage and hydrocephalus]. / Behandlung von intraventrikulären Blutungen und Hydrozephalus.

Most cases of intraventricular hemorrhage (IVH) occur secondary to spontaneous intracerebral or subarachnoid hemorrhage. The main concern is development of hydrocephalus, which is related to a poor prognosis. Over the last years, several treatment options for IVH have been introduced, but prospective data regarding the efficacy of those therapies (external ventricular drainage, intraventricular fibrinolysis, lumbar drainage, endoscopic hematoma evacuation) do not yet exist. This review focuses on combined therapy using an external ventricular drain and intraventricular fibrinolysis with r-TPA for IVH-associated initial occlusive hydrocephalus. Moreover, a continuing treatment strategy for persistent malresorptive communicating hydrocephalus using lumbar drainage is described.

Flat-panel detector volumetric CT for visualization of subarachnoid hemorrhage and ventricles: preliminary results compared to conventional CT.

INTRODUCTION: The aim of this study was to compare flat-panel volumetric CT (VCT) to conventional CT (cCT) in the visualization of the extent of subarachnoid hemorrhage (SAH) and the width of the ventricles in patients with acute SAH. METHODS: Included in the study were 22 patients with an acutely ruptured cerebral aneurysm who received VCT during coil embolization. VCT image quality, the extent of SAH (using a modified Fisher score and total slice number with SAH visible) and the width of the ventricles (Evans index) were evaluated by two experienced neuroradiologists (RAD1 and RAD2) and compared to the findings on cCT. Ten patients undergoing VCT for reasons other than SAH served as negative controls. RESULTS: Interobserver agreement in rating image quality was excellent for cCT (Kendall W value 0.94) and good for VCT (0.74). SAH was identified by RAD1 and RAD2 on VCT images in all patients. The modified Fisher scores underestimated the extent of SAH on VCT images in comparison with cCT images. Pearson's correlation coefficient (r) regarding the number of image slices with SAH visible on cCT images compared with the number on VCT images was 0.85 for RAD1 and 0.84 for RAD2. The r value for the degree of interobserver agreement for the number of slices with SAH visible was 0.99 for cCT, and 0.95 for VCT images (n=19), respectively. The width of the ventricles measured in terms of the Evans Index showed excellent concordance between the modalities (r=0.81 vs. 0.82). CONCLUSION: Our preliminary results indicate that VCT is helpful in evaluating SAH in the angiography suite. Additionally, reliable evaluation of ventricle width is feasible. However, there are limitations with regard to the visibility of SAH on VCT images in comparison to cCT images.

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.