Kirsten Schmieder

Registration of CT and Intraoperative 3-D Ultrasound Images of the Spine Using Evolutionary and Gradient-Based Methods

A system for the registration of computed tomography and 3-D intraoperative ultrasound images is presented. Three gradient-based methods and one evolutionary algorithm are compared with regard to their suitability to solve this image registration problem. The system has been developed for pedicle screw insertion during spinal surgery. With clinical preoperative and intraoperative data, it is demonstrated that precise registration is possible within a realistic range of initial misalignment. Significant differences can be observed between the optimization methods. The covariance matrix adaptation evolution strategy shows the best overall performance, only four of 12 000 registration trials with patient data failed to register correctly.

Percutaneous placement of pedicle screws in the lumbar spine using a bone mounted miniature robotic system: first experiences and accuracy of screw placement.

Study Design. A prospective analysis. Objective. The idea of this study was to evaluate a new miniature robotic system providing passive guidance for pedicle screw placement at the lumbar spine. Special focus was laid on the postoperative accuracy of screw placement. Summary and Background Data. Recent technical developments lead to a minimization of pedicle screw fixation techniques. However, the use of navigational techniques is still under controversy. Methods. Patients selected for a minimal invasive posterior lumbar interbody fusion received a spiral computer tomographic scan before surgery. The miniature hexapod robot was mounted to the spinous process and the system moves to the exact entry point according to the trajectory of the surgeon’s preoperative plan. After minimal invasive screw placement all patients received routinely a postoperative spiral computer tomographic scan. Screws placed exactly within the pedicle were evaluated as group A, screws deviating <2 mm were evaluated as group B, ≥2 mm to <4 mm (group C); ≥4 mm to <6 mm (group D); and more than 6 mm (group E). Results. Thirty-one patients received a PLIF with percutaneous posterior pedicle screw insertion using the bone mounted miniature robotic device. A total of 133 pedicle screws were placed. The majority of the screws were placed in L5 (58 screws; 43.6%). In axial plane, 91.7% of the screws were evaluated as group A and 6.8% were evaluated as group B. In longitudinal plane, 81.2% of the screws were evaluated as group A and 9.8% were evaluated as group B. In 1 screw (L5 right) the postoperative evaluation was done as group C (axial plane) and D (longitudinal plane). In 29/31 cases the integration of the miniature robotic system was successful. Conclusion. In our study the first clinical assessment of a new bone mounted robot system guiding percutaneous pedicle screw placement was done. A deviation <2 mm to the surgeon ′s plan in 91.0% to 98.5% verifies the system’s accuracy.

Detection of IDH1 mutations in gliomatosis cerebri, but only in tumors with additional solid component: evidence for molecular subtypes

The current WHO classification of brain tumors defines gliomatosis cerebri (GC) as an extensively infiltrating astrocytic glioma involving at least three cerebral lobes. The relation of GC to diffuse astrocytomas and glioblastoma is uncertain. Due to malignant biological behavior, GC is allotted to WHO grade III. Recent reports showed IDH1 mutations in astrocytic and oligodendroglial tumors WHO grades II and III and in secondary glioblastomas with a frequency of up to 90%, whereas IDH1 mutations occurred in only 5% of primary glioblastomas. Here, we examined the frequency of IDH1 mutations in 35 GC samples by direct sequencing, derived cleaved amplified polymorphic sequence analysis and immunohistochemistry. We identified IDH1 mutations in 10/24 (42%) cases, which also included a solid tumor portion (type 2 GC), but not in 11 “classical” cases without solid tumor mass (type 1 GC). TP53 mutations were revealed in two type 2 GC, but not in any type 1 GC, while combined chromosomal losses of 1p and 19q were not found at all. Our data suggest that GC consists of two histological/molecular subtypes, type 1 being clearly distinct from diffuse astrocytoma, and type 2 sharing features with diffuse astrocytoma.

Adequacy of herniated disc tissue as a cell source for nucleus pulposus regeneration

OBJECT The object of this study was to characterize the regenerative potential of cells isolated from herniated disc tissue obtained during microdiscectomy. The acquired data could help to evaluate the feasibility of these cells for autologous disc cell transplantation. METHODS From each of 5 patients (mean age 45 years), tissue from the nucleus pulposus compartment as well as from herniated disc was obtained separately during microdiscectomy of symptomatic herniated lumbar discs. Cells were isolated, and in vitro cell expansion for cells from herniated disc tissue was accomplished using human serum and fibroblast growth factor-2. For 3D culture, expanded cells were loaded in a fibrin-hyaluronan solution on polyglycolic acid scaffolds for 2 weeks. The formation of disc tissue was documented by histological staining of the extracellular matrix as well as by gene expression analysis of typical disc marker genes. RESULTS Cells isolated from herniated disc tissue showed significant signs of dedifferentiation and degeneration in comparison with cells from tissue of the nucleus compartment. With in vitro cell expansion, further dedifferentiation with distinct suppression of major matrix molecules, such as aggrecan and Type II collagen, was observed. Unlike in previous reports of cells from the nucleus compartment, the cells from herniated disc tissue showed only a weak redifferentiation process in 3D culture. However, propidium iodide/fluorescein diacetate staining documented that 3D assembly of these cells in polyglycolic acid scaffolds allows prolonged culture and high viability. CONCLUSIONS Study results suggested a very limited regenerative potential for cells harvested from herniated disc tissue. Further research on 2 major aspects in patient selection is suggested before conducting reasonable clinical trials in this matter: 1) diagnostic strategies to predict the regenerative potential of harvested cells at a radiological or cell biology level, and 2) clinical assessment strategies to elucidate the metabolic state of the targeted disc.

Non-fusion rates in anterior cervical discectomy and implantation of empty polyetheretherketone cages.

Study Design. A prospective analysis. Objective. Our aim was to assess the radiographically detectable bony fusion in patients with anterior cervical discectomy (ACD) and polyetheretherketone (PEEK)-cage implantation without additional filling. Furthermore, clinical data of patients with and without fusion were compared. Summary of Background Data. PEEK-cage implantation is performed in cervical spinal surgery because of its benefits. However, fusion rates without filling of the cage have not been reported. Methods. Patients selected for ACD with PEEK-cage implantation prospectively underwent plain radiography in anterior-posterior and lateral projections during the postoperative hospital stay and at follow-up. Furthermore, clinical status was evaluated using the Odom scale, the Short Form-36, the Visual Analog Scale (VAS) for arm and neck pain, and the cervical Oswestry score. Fusion status, migration, and subsidence of the PEEK cage were evaluated on the basis of the lateral radiographs. Fusion was confirmed by presence of continuous trabecular bone bridges in the disc space. To exclude an influence of the cage on the evaluation of fusion rates, fusion was evaluated in analogous fashion retrospectively in a control group. Results. A total of 52 patients underwent ACD and interbody fusion. One-level surgery was performed in 44 patients and 2-level surgery in 8 patients. A total of 60 ACD and interbody fusions with a PEEK cage were analyzed. A majority of operations were at the C5/6 level (40 patients, 77%). Cage height was 4 mm in 32 cases, 5 mm in 23 cases, and 6 mm in 5 cases. Bony fusion was present at 43 treated levels (71.7%), whereas at 17 levels (28.3%) no fusion was found. Statistical analysis revealed no significant difference between the fusion and non-fusion groups regarding time to follow-up, implanted cage height. Short Form-36, cervical Oswestry score, VAS arm and neck, or Odom criteria. In the control group, ACD was performed in 29 patients (42 levels; 18 one-level and 12 two-level operations). Bony fusion was present at 30 levels (71.4%), whereas non-fusion was present at 12 treated levels (28.6%). Statistically analysis revealed no significant difference between the study group and the control group regarding time to follow-up or fusion rates. Conclusion. Implantation of empty PEEK cages after ACD shows an unexpectedly low rate effusion according to radiologic criteria, although no statistically significant difference could be observed clinically.

Vibrography During Tumor Neurosurgery

The aim of this study was to determine whether elastography, a sonographically based real‐time strain imaging method for registering the elastic properties of tissue, can be used in brain tumor surgery.

Pharmacokinetic studies of 68Ga-labeled bombesin ( 68Ga-BZH3) and F-18 FDG PET in patients with recurrent gliomas and comparison to grading: Preliminary results

Purpose: Dynamic PET studies with a 68Ga-Bombesin analog, the 68Ga-BZH3, were performed in patients with highly suspected recurrent gliomas to investigate the effect of the receptor scintigraphy on tumor grading. Furthermore, dynamic F-18 Fluorodeoxyglucose (FDG) studies were performed for comparison. Methods: The study consisted of 15 patients with histologically confirmed recurrent gliomas. Dynamic PET scans using 68Ga-BZH3 and FDG were obtained on 2 different days within 1 week. Multivariate analysis was used for the evaluation of the kinetic data. Standardized uptake values were calculated and a compartment (2-tissue) as well as a noncompartment model was used for data evaluation of both tracers. Results: The evaluation includes 6 patients with a WHO II, 6 patients with a WHO III, and 3 patients with a WHO IV recurrent gliomas. Of the 15 patients, 10 patients demonstrated an increased 68Ga-BZH3 uptake visually, 3 of them with a WHO II, 4 with a WHO III, and 3 with a WHO IV tumor. Of the 15 patients, 6 patients revealed an enhanced FDG metabolism visually, 3 of them with a WHO II, and 3 with a WHO III. None of the 3 patients with WHO IV tumor demonstrated an enhanced FDG-uptake. Discriminant analysis based on a combination of FDG influx and binding potential of 68Ga-BZH3 best discriminated between low- and high-grade gliomas with a correct classification rate of 100%. Conclusions: 68Ga-BZH3 seems to be helpful in patients with recurrent gliomas for the differentiation between low- and high-grade gliomas. Overall, the quantitative evaluation was superior to the visual analysis and the parameters of the 68Ga-BZH3 kinetics were more helpful than those of FDG for the differentiation between low- and high-grade gliomas.

Intracerebral abscess after abutment change of a bone anchored hearing aid (BAHA).

Objective Brain abscesses are life-threatening and sometimes difficult to detect. A brain abscess after placement, manipulation of a bone anchored hearing aid, or a periauricular implant for fixation of an ear prosthesis has never been reported in the literature. Patient A 42-year-old man suffered from a right-sided temporodorsal brain abscess after change of a bone anchored hearing aid abutment. The fixture itself had been inserted 8 years before without any complications in the peri- or postoperative period. A CT-guided puncture of the abscess could be performed via the screw-hole in the temporal bone after removal of the fixture, and the patient was treated with antibiotics. Results The outcome of the procedure was good without neurologic deficits for the patient. Conclusion The insertion of periauricular screw implants bears the risk of meningeal lesions as well as a small risk of purulent intracranial and intracerebral complications perioperatively or in the context of later manipulations. Minimally invasive therapy of such brain abscesses can be performed by removal of the foreign body, CT-guided puncture, and antibiotic medication.

High prevalence of heterotopic ossification after cervical disc arthroplasty: outcome and intraoperative findings following explantation of 22 cervical disc prostheses

OBJECT Cervical disc arthroplasty (CDA) has been increasingly used for the treatment of cervical disc herniations. However, the impact of CDA on adjacent-segment degeneration and the degree of heterotopic ossification (HO) of the treated segment remain a subject of controversy. Due to a product failure of the Galileo-type disc prosthesis, 22 of these devices were explanted. The radiological and clinical course in each case was investigated in detail with an emphasis on the incidence of HO and facet joint degeneration 18 months following the operation. Intraoperative findings regarding ossification and implant fixation were documented. Thus, the authors were able to describe the true rate of adjacent-segment degeneration and HO following CDA and the clinical relevance thereof. METHODS In all 22 patients, functional radiographic imaging was performed prior to surgery, 3 and 12 months after surgery, and prior to disc prosthesis explantation. At all time points, the range of motion (ROM) in the operated and adjacent segments was determined. A motion index was calculated using the preoperative and all postoperative ROMs (preoperative ROM/postoperative ROM). Computed tomography was used preoperatively to measure the height of the index segment, extent of HO, and the degree of the progression of facet arthrosis, and was used postoperatively prior to prosthesis explantation. Patients completed clinical questionnaires that included a visual analog scale and the Neck Disability Index. RESULTS The motion index of the index segment declined gradually from 1.4 at 3 months postoperative to 1.2 prior to explantation, while the motion index of the adjacent upper segment increased from 0.9 to 1.3. The mean ROM of the index segment was 10.4° ± 6.7°, and fusion was observed in 2 (9%) of the 22 patients. Prosthesis migration was present in 3 patients (13.6%). Severe HO (Grades 3 and 4) was present in 17.4%. Computed tomography showed a significant increase of segmental height of the index segment (1.6 ± 1.1 mm, p = 0.035), and a significant increase of left-sided lateral osteophytes (1.7 ± 2.1 mm, p = 0.009). The incidence of severe osteophyte formation (> 2 mm) occurred in 40%. Intraoperative findings reflected the results from CT, with primary lateral proliferation of osteophytes found in approximately 25% of patients. The mean visual analog scale scores were 3.8 ± 2.7 (neck) and 2.4 ± 2.5 (arms), and the mean Neck Disability Index score was 30 ± 22. No correlation was found between radiological and clinical parameters. CONCLUSIONS In this study, a higher incidence of HO after CDA could be demonstrated using CT, compared with studies using fluoroscopy only. However, patient selection and/or the operative technique might have contributed to the high prevalence of osteophyte formation. Thus, the exact indication for CDA has to be reconsidered. Because implant migration was detected, using fixation in the present CDA model appears suboptimal.

The chemokines CXCL10 and XCL1 recruit human annulus fibrosus cells.

Study Design. Human annulus fibrosus tissue and cells were analyzed for the presence of chemokine receptors and the migratory effect of selected chemokines. Objective. To investigate spontaneous repair mechanisms and underlying cell recruitment in response to annular tears and degenerative defects. Summary of Background Data. Resorption of herniated disc tissue and the attempt to close annulus tears with repair tissue occur spontaneously. Although chemokines are suggested to play a role in resorption of herniated disc tissue, the role of chemokines in annulus fibrosus homeostasis and repair remains unclear. Methods. Cells were isolated from annulus fibrosus tissue and expanded in the presence of human serum. Multiwell chemotaxis assays were used to analyze the migratory effect of human serum and 0 to 1000 nM concentrations of the chemokines CXCL7, CXCL10, CXCL12, CCL25, and XCL1 on annulus fibrosus cells (AFCs) (n = 9 per chemokine and dose). Presence of corresponding chemokine receptors in AFCs was determined by real-time polymerase chain reaction analysis and immunohistochemistry. Results. Serum (0.1%–10%) significantly (P < 0.01) stimulates the migration of AFCs. Compared with untreated cells, the migration of cells was significantly (P < 0.01) enhanced upon stimulation with 100 to 1000 nM CXCL10 and 1000 nM XCL1. Chemokine receptors showed low expression levels in expanded AFCs as assessed by polymerase chain reaction. Immunohistochemical staining of the CXCL10 receptor CXCR3 and the XCL1 receptor XCR1 showed that the presence of the particular receptors in AFCs expanded under conventional cell culture conditions. In native annulus fibrosus tissue, CXCR3 was evident, whereas XCR1 could not be detected. Conclusion. The findings suggest that chemokines, in particular CXCL10, effectively recruit isolated AFCs. This suggests that chemokines are involved in annulus fibrosus homeostasis and potentially in spontaneous annulus repair attempts. This might have important implications for biological annulus-sealing strategies.