Exploring complications following cranioplasty after decompressive hemicraniectomy: A retrospective bicenter assessment of autologous, PMMA and CAD implants.

Cranioplasty (CP) after decompressive hemicraniectomy (DHC) is a common neurosurgical procedure with a high complication rate. The best material for the repair of large cranial defects is unclear. The aim of this study was to evaluate different implant materials regarding surgery related complications after CP. Type of materials include the autologous bone flap (ABF), polymethylmethacrylate (PMMA), calcium phosphate reinforced with titanium mesh (CaP-Ti), polyetheretherketone (PEEK) and hydroxyapatite (HA). A retrospective, descriptive, observational bicenter study was performed, medical data of all patients who underwent CP after DHC between January 1st, 2016 and December 31st, 2022 were analyzed. Follow-up was until December 31st, 2023. 139 consecutive patients with a median age of 54 years who received either PMMA (56/139; 40.3%), PEEK (35/139; 25.2%), CaP-Ti (21/139; 15.1%), ABF (25/139; 18.0%) or HA (2/139; 1.4%) cranial implant after DHC were included in the study. Median time from DHC to CP was 117 days and median follow-up period was 43 months. Surgical site infection was the most frequent surgery-related complication (13.7%; 19/139). PEEK implants were mostly affected (28.6%; 10/35), followed by ABF (20%; 5/25), CaP-Ti implants (9.5%; 2/21) and PMMA implants (1.7%, 1/56). Explantation was necessary for 9 PEEK implants (25.7%; 9/35), 6 ABFs (24.0%; 6/25), 3 CaP-Ti implants (14.3%; 3/21) and 4 PMMA implants (7.1%; 4/56). Besides infection, a postoperative hematoma was the most common cause. Median surgical time was 106 min, neither longer surgical time nor use of anticoagulation were significantly related to higher infection rates (p = 0.547; p = 0.152 respectively). Ventriculoperitoneal shunt implantation prior to CP was noted in 33.8% (47/139) and not significantly associated with surgical related complications. Perioperative lumbar drainage, due to bulging brain, inserted in 38 patients (27.3%; 38/139) before surgery was protective when it comes to explantation of the implant (p = 0.035). Based on our results, CP is still related to a relatively high number of infections and further complications. Implant material seems to have a high effect on postoperative infections, since surgical time, anticoagulation therapy and hydrocephalus did not show a statistically significant effect on postoperative complications in this study. PEEK implants and ABFs seem to possess higher risk of postoperative infection. More biocompatible implants such as CaP-Ti might be beneficial. Further, prospective studies are necessary to answer this question.

Simultaneous Interference with HER1/EGFR and RAC1 Signaling Drives Cytostasis and Suppression of Survivin in Human Glioma Cells in Vitro.

We have previously reported that combined inhibition of the epidermal growth factor receptor by erlotinib and of RAC1 by NSC23766 yielded a synergistic antiproliferative effect on established and primary cultured glioblastoma cells. The current study aimed at identifying the molecular mechanism. Staining for annexin V/PI or carboxyfluorescein succinimidyl ester was performed in order to determine the induction of apoptosis, necrosis or cytostasis in established and primary cultured glioblastoma cells. Moreover, expression of Ki-67 was determined by immunofluorescence, and the expression of cell cycle proteins was analysed by Western blot. Our data show that combined treatment with erlotinib and NSC23766 resulted in a reduced number of cell divisions, a significantly decreased Ki-67 expression, increased apoptosis and autophagy when compared to single agent treatments. On the molecular level, concomitant treatment with both agents resulted in a pronounced downregulation of cyclin D1, cyclin-dependent kinases 2, 4 and 6, as well as of survivin when compared to treatments with either agent alone. In conclusion, we demonstrate that combined treatment of human glioma cell lines in vitro with erlotinib and NSC23766 markedly inhibits cell division, induces apoptosis independent of caspase-3 activation and induces autophagy concomitant with suppression of survivin.

Intraoperative magnetic resonance imaging.

Intraoperative magnetic resonance imaging is a widely accepted method for resection control of glial tumors. Increasingly, it is also used during the resection of skull base tumors. Several studies have independently demonstrated an increase in the extent of resection in these tumors with improved prognosis for the patients. Technical innovations combined with the easier operation of this imaging modality have led to its widespread implementation. The development of digital image processing has also brought other modalities such as ultrasound and computed tomography to the focus of skull base surgery.

[Intraoperative navigation, with focus on the skull base]. / Intraoperative Navigation mit Fokus auf der Schädelbasis.

Intraoperative navigation systems are widely used in ENT, oral and maxillofacial, and neurosurgery. The benefits of such systems have been demonstrated in various applications, including intracranial and skull base surgery. Intraoperative shift, "brain shift" and changes in anatomy caused by the surgical procedure itself impair the accuracy of navigation and represent factors limiting its application, particularly in glioma and metastatic brain surgery. For this reason, intraoperative imaging was incorporated into neurosurgery. A specific application of navigation is thus skull base surgery, where shifts are often negligible due to the bony structures in which pathologies are embedded. Development of new systems with seamless integration into the operative workflow propagated routine use of navigation in neuro- and ENT surgery. Navigation proved especially helpful in interdisciplinary surgery with pathologies located in anatomic regions where competences of different surgical disciplines overlap, as in the skull base. While this increased radicality in tumour resection, there was a high risk of morbidity. The integration of electrophysiological function monitoring served to preserve function and reduce morbidity, and has led to less invasive and radical strategies in skull base surgery. New radiosurgical methods to adjuvantly treat possible tumour remnants have also supported this development. Systems allowing resection borders to be marked in the navigational coordinates would enable direct linking of these data to radiotherapy planning and better interpretation of follow-up imaging. Navigation is thus a valuable tool supporting interdisciplinary cooperation in skull base surgery for the benefit of patients.

CD95 maintains stem cell-like and non-classical EMT programs in primary human glioblastoma cells.

Glioblastoma (GBM) is one of the most aggressive types of cancer with limited therapeutic options and unfavorable prognosis. Stemness and non-classical epithelial-to-mesenchymal transition (ncEMT) features underlie the switch from normal to neoplastic states as well as resistance of tumor clones to current therapies. Therefore, identification of ligand/receptor systems maintaining this privileged state is needed to devise efficient cancer therapies. In this study, we show that the expression of CD95 associates with stemness and EMT features in GBM tumors and cells and serves as a prognostic biomarker. CD95 expression increases in tumors and with tumor relapse as compared with non-tumor tissue. Recruitment of the activating PI3K subunit, p85, to CD95 death domain is required for maintenance of EMT-related transcripts. A combination of the current GBM therapy, temozolomide, with a CD95 inhibitor dramatically abrogates tumor sphere formation. This study molecularly dissects the role of CD95 in GBM cells and contributes the rational for CD95 inhibition as a GBM therapy.

[Intraoperative magnetic resonance imaging. Fifteen years' experience in the neurosurgical hybrid operating suite]. / Intraoperative Magnetresonanztomographie. Erfahrungen aus 15 Jahren Hybridoperationssaal in der Neurochirurgie.

Intraoperative magnetic resonance imaging was established 15 years ago due to special requirements for the resection of cerebral gliomas. Several studies have independently shown an increase of the extent of resection of the tumor and also an improved survival of the patients. Technical innovations combined with an easier operation of this imaging modality led to widespread implementation of this method. The introduction of functional and metabolic imaging opened up new prospects of further improving the therapeutic outcome.

Lows and highs: 15 years of development in intraoperative magnetic resonance imaging.

Intraoperative magnetic resonance imaging (ioMRI) during neurosurgical procedures was first implemented in 1995. In the following decade ioMRI and image guided surgery has evolved from an experimental stage into a safe and routinely clinically applied technique. The development of ioMRI has led to a variety of differently designed systems which can be basically classified in one- or two-room concepts and low- and high-field installations. Nowadays ioMRI allows neurosurgeons not only to increase the extent of tumor resection and to preserve eloquent areas or white matter tracts but it also provides physiological and biological data of the brain and tumor tissue. This article tries to give a comprehensive review of the milestones in the development of ioMRI and neuronavigation over the last 15 years and describes the personal experience in intraoperative low and high-field MRI.

Image guided aneurysm surgery in a Brainsuite® ioMRI Miyabi 1.5 T environment.

OBJECTIVE: Current literature only gives sparse account of aneurysm surgery in an intraoperative MRI environment. After installation of a BrainSuite(®) ioMRI Miyabi 1.5 T at our institution the aim of the present preliminary study was to evaluate feasibility, pros and cons of aneurysm surgery in this special setting. MATERIAL AND METHODS: Since February 2009, during a 3 months period we performed elective image guided aneurysm surgery in 4 ACM and 1 ACOM aneurysm (four patients) in this ioMRI setting. The patients' heads were rigidly fixed in the Noras 8-Channel OR Head Coil. Our imaging protocol included MP-RAGE, T2-TSE axial, TOF-MRA and diffusion-/perfusion-imaging immediately before surgery and after clip application. Presurgical 3D-planning was performed using the iPlan®-Software. RESULTS: All five aneurysms were operated without temporary clipping. There were no intra- or postoperative complications. Patient positioning and head fixation with the integrated Noras Head Clamp was feasible, but there were significant limitations particularly with regard to more complex approaches and patient physiognomy. Image quality especially TOF-MRA was good in 4, insufficient in 1 aneurysm. Presurgical planning especially vessel extraction from TOF-MRA was possible but certainly needs significant future improvement. Diffusion- and perfusion weighted examinations yielded good image quality. CONCLUSION: Our limited experience is encouraging so far. Further improvement particularly concerning flexibility of patient positioning and presurgical 3D-planning for vascular procedures is most necessary. As a future perspective image guided aneurysm surgery in an ioMRI-environment may be helpful especially in complex aneurysms and provide neurosurgeons and neuroanaesthesiologists with additional information about cerebral haemodynamics and perfusion pattern in the vascular territory distal to the target vessel.

Intraoperative MRI for interventional neurosurgical procedures and tumor resection control in children.

INTRODUCTION: Despite the introduction of neuronavigational systems, radical tumor removal is still problematic in many neurosurgical procedures. Thus, direct intraoperative imaging for tumor resection control was implemented with an intraoperative magnetic resonance imaging (ioMRI) scanner installed in the operating room. Whereas most procedures with ioMRI were carried out in adults, we summarize 7 years of experience using ioMRI in children for interventional neurosurgical procedures or for tumor resection control. METHOD: An open magnetic resonance scanner (Magnetom Open 0.2 T) was installed in the neurosurgical operating room. For tumor resection control, ioMRI was performed in 35 procedures. After the ioMRI scans were analyzed with respect to quality, the identification of residual tumor was considered by the attending neuroradiologist and neurosurgeon. If residual tumor tissue was present, a new three-dimensional (3D) dataset was acquired to update the neuronavigation; subsequently, the tumor resection was extended. In all these procedures, the results of the ioMRI were checked by an early postoperative high-field magnetic resonance imaging (MRI) study. In addition, ioMRI was carried out in ten other children to monitor interventional neurosurgical procedures. RESULTS: In all children, ioMRI was adequate both for tumor resection control and monitoring of interventional procedures. Primary radical removal of tumor was reached in 40% as confirmed by ioMRI, but in 60% of the patients, the tumor resection procedure was extended after residual tumor was detected using the new 3D dataset for navigational update. By using ioMRI, radical tumor removal improved up to 83% as confirmed by early postoperative MRI. Procedure-related complications were not seen in our series. For all MR-guided biopsies, histology findings could be confirmed, and aspiration of intracranial cysts or abscesses could be monitored online. CONCLUSION: IoMRI using the open magnetom is suitable for detecting residual tumor tissue, can compensate for the phenomenon of brain shift using a new intraopertive 3D dataset for extended tumor resection, and is capable of monitoring interventional neurosurgical procedures. By using ioMRI for tumor resection control, the degree of tumor resection could be significantly improved.

3D ultrasound navigation in syrinx surgery - a feasibility study.

BACKGROUND: The prototype of a 3D ultrasound navigation system, with a trackable 4- to 8-MHz phased-array ultrasound probe was used in syrinx-surgery. The aim of this study was to evaluate the advantages offered by 3D ultrasound and navigation in syringomyelial surgery. METHODS AND MATERIALS: After laminectomy, with a free-handed tilt of the ultrasound probe, the 3D volume of the target area is acquired within 15 seconds. The data are visualized after reconstruction in an axial, coronal, and sagittal view, offering the possibility of ultrasound-based guided surgery. RESULTS: Based on the intraoperative volume information, it was possible to navigate with the 3D ultrasound images in all cases. The orientation and image quality with respect to resolution, spatial information, and the identification of anatomical structures facilitated the surgery in all seven cases. The navigation tool, with a length of 12 cm and a tip diameter of 1 mm, was simple to place into the surgical site. The availability of an up-to-date 3D-image resulted in less interruption of the surgical procedure, with no need to repeatedly fill the cavity with sterile saline for new ultrasound acquisitions. New ultrasound images were only required if shift occurred. The coronal and "trajectory-plane" views, offer additional information about the syrinx cavity. The target borders are easier to determine and orientation in separated cavities was possible. Particularly in syringomyelial surgery it was helpful to determine the surface point of the syrinx to place the myelotomy or insert a catheter. CONCLUSION: 3D ultrasound offers the advantages of visualizing the third dimension of the target. For orientation and border determination navigation within the 3D ultrasound volume is very helpful and can take place with the ultrasound probe out of the way. Any disruption in the surgical procedure is minimized by not having to repeatedly fill the cavity with a sterile saline solution, there are fewer difficulties with image orientation because of new image adjustments.

Treatment of trigeminal neuralgia associated with multiple sclerosis: case report.

The incidence of trigeminal neuralgia (TN) in patients with multiple sclerosis is higher than in the general population. If pharmacologic therapy fails, invasive procedures in the gasserian ganglion are usually offered. Microvascular decompression is not routinely performed. The authors report a patient with persistent TN after repetitive trigeminal radiofrequency rhizotomy and finally successful microvascular decompression after demonstration of neurovascular compression with high-resolution MRI.

High-resolution laser surface scanning for patient registration in cranial computer-assisted surgery.

OBJECTIVE: Markerless patient registration is a new procedure that may reduce logistical efforts and possibly also the radiation load on the patients prior to a computer-assisted intervention. Congruent surfaces, such as bone surfaces or skin surfaces, represented in a data set and in the surgical site, can be overlapped using surface-matching. Previous studies describing this kind of markerless registration, however, show inaccuracies of up to 10 mm during computer-assisted navigation. Furthermore, these systems use less than 1000 surface points of the soft tissue surface in order to establish a correlation between the patient and the data set. Previous papers did not answer the question whether it is this scanning resolution that induces these inaccuracies in registration or rather intraoperative skin deformations. STUDY DESIGN: In the present study therefore a new navigation system (SSN++) was used which is able to register up to 180,000 surface points of the surgical site. SSN++ is an infrared navigation system enlarged by a Minolta VI 900 3D volume digitizer. Three different kinds of laser scan-resolution were used for data correlation. An additional congruence analysis was performed in order to assess the geometry of the matched skin surfaces. 22 patients suffering from different cranial diseases (tumors, bony malformations, foreign bodies) were prepared for a computer-assisted intervention. Intraoral titanium-markers, rigidly fixed on the patients by a maxillary splint, were placed as targets while the CT data sets were made. These targets were - after markerless laser scan registration of the patients - supposed to serve for validating the new high-resolution navigation system SSN++. RESULTS: The accuracy of markerless laser scan registration depends on the intraoperative laser scan's resolution. A high accuracy of the data correlation can be achieved if the number of the laser scan cloud points is about the same as the number of voxels of the corresponding surface on the CT data set. A reduction of the laser scan cloud points to less than 10 % compared to the number of voxels of the CT surface, however, leads to a significant loss of accuracy after markerless patient registration. CONCLUSION: The markerless laser scan registration of the surgical site may achieve the same accuracy as a patient registration made by rigidly fixed titanium screws (mean accuracy: 1.2 mm) as long as a high-resolution laser scan is being used.

A flexible registration framework for multimodal image data.

This paper describes a registration framework based on the insight segmentation and registration toolkit (ITK) which can be used for matching multimodal image data. Different target groups with individual needs and precognition are addressed. The framework offers tools for supporting different matching tasks in a clinical environment. A setup editor defines specific rigid or non rigid matching approaches and the appropriate parameters. Different metrics including a correlation metric, a difference metric and mutual information based metrics are available. Furthermore, a test series editor can be used to evaluate the selected setup. The evaluation results, which are expressed in statistical figures, trends and performance measures, can be visualized and used for an optimal adapted setup configuration. Tests for matching precision, quality and parameter adjustments are offered. For export and import of image data, the most frequently used file formats of clinical environments like DICOM and ANALYZE are supported. We demonstrate some registration examples which frequently occur in the neurosurgical routine of a University Hospital.

[A computer system for planning and carrying out neurosurgical interventions]. / Ein Computersystem zur Planung und Durchführung Neurochirurgischer Interventionen.

Neurosurgical interventions have to be planned carefully using different sources of information like anatomical MR images, segmented brain structures, functional data (EEG, MEG, fMRI) and atlas information. We developed a 3D planning system that incorporates this important data. The planning procedure is performed by the neurosurgeon in less than 15 minutes. The results of the planning phase, i.e. an optimal trajectory, localizations of the electrical sources and information about the brain tissue can be used intraoperatively. Therefore the planning system is connected with a navigation system. The simultaneous visualization of the planning information and the actual position of the instrument during the surgical procedure is extremely valuable for the outcome and quality of the intervention.

Initial experience with an ultrasound-integrated single-RACK neuronavigation system.

A prototype ultrasound-integrated neuronavigation system was tested in 34 operations as regards image quality, stability, and handling during daily use in the operating theatre. The system consists of a high-end ultrasound scanner, a navigation computer, and an active optical positioning and digitiser system, all integrated in a single rack. An Ethernet interface between the two hardware devices enables digital data transfer between the ultrasound scanner and the navigation device without loss of image quality. The integration of an ultrasound scanner and a navigation device offers the opportunity of navigating directly to an intracranial or intraspinal lesion using intra-operative 3D ultrasound images. The brainshift problem is thus avoided. The ability to directly compare MR images and 3D ultrasound simplifies the interpretation of ultrasound images. The single-rack solution is an advantage in times of restricted space in the operating theatre caused by the increasing volume of technical equipment needed for a neurosurgical operation. In 30 cases the prototype system showed good reliability. In four cases the navigation system failed during the operation; however, the capacity of the ultrasound scanner was still available as a stand-alone function. With the single-rack concept, the flexibility of the system is high and the complete device can easily be moved from one operating theatre to another.

Low-field interventional MRI in neurosurgery: finding the right dose of contrast medium.

MRI is increasingly being used as an interventional tool in neurosurgery. The field strength of "intraoperative" MR systems is usually lower than that of imagers commonly used for diagnostic purposes. However, lesion enhancement and apparent lesion extent depend on field strength. The aim of this study was to compare the contrast between intracranial, contrast-enhancing space-occupying lesions and the surrounding white matter obtained with low-field (0.2 T) and high-field (1.5 T) MR imaging and to find the contrast medium dosage for low-field MRI that produces the same lesion-to-white-matter contrast as the one obtained with high-field MRI after the administration of a standard dose of the contrast medium. A total of 38 patients with intracranial metastases or high-grade glioma were enrolled in this study. T1-weighted spin-echo sequences were acquired. High-field (1.5 T) studies were performed after the i.v. administration of 0.1 mmol gadolinium-DTPA/kg body weight. For low-field MRI (0.2 T) a dose escalation technique was used. T1-weighted sequences were repeated after each of three i. v. injections of 0.1 mmol gadolinium-DTPA/kg body weight. Thus, at the low-field examinations three T1-weighted sequences with a contrast medium dosage of 0.1, 0.2 and 0.3 mmol gadolinium-DTPA/kg body weight were obtained. Lesion-to-white-matter contrasts were calculated and compared. The average lesion-to-white-matter contrast obtained with high-field MR examinations was 1.63 (standard deviation 0.32). In the low-field MR examinations the average lesion-to-white-matter contrast was 1.34 (0.2) after a single dose, 1.57 (0.2) after a double dose, and 1.71 (.19) after a triple dose of contrast medium. The lesion-to-white-matter contrast of the high-field MR examination after a single dose of contrast medium was significantly higher than that of the low-field study after a single dose (P < 0.0001), but did not differ significantly from the low-field studies after a double (P = 0.28) or a triple dose (P = 0.17) of contrast medium. In a series of patients with contrast-enhancing space occupying brain lesions low-field MRI (0.2 T) after a double dose of contrast medium yielded the same lesion-to-white-matter contrasts as high-field MRI (1.5 T) after a standard dose. This is an important finding to avoid errors in intraoperative MRI due to the immanently lower degree of lesion enhancement in low-field MR imaging.

Monocrystalline iron oxide nanoparticles: possible solution to the problem of surgically induced intracranial contrast enhancement in intraoperative MR imaging.

BACKGROUND AND PURPOSE: Intraoperative MR imaging is increasingly being used to control the extent of surgical resection; however, surgical manipulation itself causes intracranial contrast enhancement, which is a source of error. Our purpose was to investigate the potential of monocrystalline iron oxide nanoparticles (MIONs) to solve this problem in an animal model. METHODS: In male Wistar rats, surgical lesions of the brain were produced. The animals underwent MR examination immediately afterward. In the first group, a paramagnetic contrast agent was administered, whereas the second group of animals received MIONs 1 day before surgery. In a third group of animals, malignant glioma cells were stereotactically implanted in the caudoputamen. Two weeks later, MIONs were IV injected and the tumor was (partially) resected. Immediately after resection, MR examination was performed to determine the extent of residual tumor. RESULTS: Surgically induced intracranial contrast enhancement was seen in all animals in which a paramagnetic contrast agent was used. Conversely, when MIONs had been injected, no signal changes that could be confused with residual tumor were detected. In the animals that had undergone (partial) resection of experimental gliomas, MR assessment of residual tumor was possible without any interfering surgically induced phenomena. CONCLUSION: Because MIONs are stored in malignant brain tumor cells longer than they circulate in the blood, their use offers a promising strategy to avoid surgically induced intracranial contrast enhancement, which is known to be a potential source of error in intraoperative MR imaging.

Comparison of intraoperative MR imaging and 3D-navigated ultrasonography in the detection and resection control of lesions.

OBJECT: The authors undertook a study to compare two intraoperative imaging modalities, low-field magnetic resonance (MR) imaging and a prototype of a three-dimensional (3D)-navigated ultrasonography in terms of imaging quality in lesion detection and intraoperative resection control. METHODS: Low-field MR imaging was used for intraoperative resection control and update of navigational data in 101 patients with supratentorial gliomas. Thirty-five patients with different lesions underwent surgery in which the prototype of a 3D-navigated ultrasonography system was used. A prospective comparative study of both intraoperative imaging modalities was initiated with the first seven cases presented here. In 35 patients (70%) in whom ultrasonography was performed, accurate tumor delineation was demonstrated prior to tumor resection. In the remaining 30% comparison of preoperative MR imaging data and ultrasonography data allowed sufficient anatomical localization to be achieved. Detection of metastases and high-grade gliomas and intraoperative delineation of tumor remnants were comparable between both imaging modalities. In one case of a low-grade glioma better visibility was achieved with ultrasonography. However, intraoperative findings after resection were still difficult to interpret with ultrasonography alone most likely due to the beginning of a learning curve. CONCLUSIONS: Based on these preliminary results, intraoperative MR imaging remains superior to intraoperative ultrasonography in terms of resection control in glioma surgery. Nevertheless, the different features (different planes of slices, any-plane slicing, and creation of a 3D volume and matching of images) of this new ultrasonography system make this tool a very attractive alternative. The intended study of both imaging modalities will hopefully allow a comparison regarding sensitivity and specificity of intraoperative tumor remnant detection, as well as cost effectiveness.