Variants of the Anterior Subtemporal Approach to the Gasserian Ganglion and Related Structures: An Anatomical Study With Relevant Implications for Keyhole Surgery.

BACKGROUND: The advantages and limitations of different craniotomy positions and approach trajectories to the gasserian ganglion (GG) and related structures using an anterior subtemporal approach have not been studied systematically. Knowledge of these features is of importance when planning keyhole anterior subtemporal (kAST) approaches to the GG to optimize access and minimize risks. METHODS: Eight formalin-fixed heads were used bilaterally to assess temporal lobe retraction (TLR), trigeminal exposure, and relevant anatomical aspects of extra- and transdural classic anterior subtemporal (CLAST) approaches compared with slightly dorsally and ventrally allocated corridors. RESULTS: TLR to the GG and foramen ovale was found to be lower via the CLAST approach (P < 0.001). Using the ventral variant, TLR to access the foramen rotundum was minimized (P < 0.001). The overall TLR was maximal using the dorsal variant (P < 0.001) owing to interposition of the arcuate eminence. An extradural CLAST approach required wide exposure of the greater petrosal nerve (GPN) and middle meningeal artery (MMA) sacrifice. Both maneuvers were spared using a transdural approach. Using CLAST, medial dissection >39 mm can enter the Parkinson triangle, jeopardizing the intracavernous internal carotid artery. The ventral variant enabled access to the anterior portion of the GG and foramen ovale without the need for MMA sacrifice or GPN dissection. CONCLUSIONS: The CLAST approach provides high versatility to approach the trigeminal plexus, minimizing TLR. However, an extradural approach jeopardizes the GPN and requires MMA sacrifice. The risk of cavernous sinus violation exists when progressing medially beyond 4 cm. The ventral variant has some advantages to access the ventral structures and avoid MMA and GPN manipulation. In contrast, the usefulness of the dorsal variant is rather limited owing to the greater TLR required.

Endoscopic-assisted paramedian supracerebellar infratentorial approach to the posterior portion of the third ventricle. Anatomical study and surgical cases.

BACKGROUND: To date, morphometrical data providing a systematic quantification of accessibility and operability parameters to the boundaries of the posterior portion of the third ventricle (PTV) when applying an endoscopic-assisted paramedian supracerebellar infratentorial approach (EPSIA) are lacking. We performed an anatomical study and complemented our findings with surgical cases. METHODS: Eight EPSIAs towards the PTV were performed in cadaveric specimens. Optimal approach angles (OA), surgical freedom (SF) and operability indexes (Oi) to the PTV boundaries were assessed. Additionally, a 54-year-old man and 33-year-old woman were operated on PTV tumors applying the EPSIA. RESULTS: Sagittal OA to ventricle's roof and floor was 36±1.4° and 25.5±3.5° respectively, axial OA to the ipsilateral and contralateral ventricle's wall were 9.5±1.3° and 28.5±1.6°. SF was maximal on the contralateral wall (121.2±19.3mm2), followed by the roof (112.7±18.8mm2), floor (106.6±19.2mm2) and ipsilateral wall (94.1±15.7mm2). SF was significantly lower along the ipsilateral compared the contralateral wall (p<0.01) and roof (p<0.05). Facilitated surgical maneuvers with multiangled exposure were possible up to 8.5±1.07mm anterior to ventricle's entrance, whereas surgical maneuvers were possible but difficult up to 15.25±3.7mm. Visualization of more anterior was possible up to a distance of 27±2.9mm, but surgical maneuvers were barely feasible. EPSIA enabled successful resection of both PTV tumors and postoperative course was uneventful. CONCLUSIONS: EPSIA can be effective for approaching the PTV, enabling surgery along all boundaries, but especially on its roof and contralateral wall. In the not-enlarged ventricle, surgical maneuvers are feasible up to the level of the Monro foramen, becoming more limited anteriorly.

Two-stage endoscopic assisted approach for large pineal region and falcotentorial meningioma: first stage paramedian supracerebellar infratentorial approach, second stage interhemispheric occipital transtentorial approach: surgical cases and anatomical study.

Resection of complex falcotentorial meningiomas, growing along the pineal region (PR), and posterior incisural space (PIS) represents a neurosurgical challenge. Here, we present our strategy for effective resection of large falcotentorial meningiomas applying a paramedian supracerebellar infratentorial and interhemispheric occipital transtentorial approach in staged surgeries. We further systematically compared the effectiveness of midline (MSIA) and paramedian (PSIA) supracerebellar infratentorial, as well as interhemispheric occipital transtentorial approaches (IOTA) to operate along the PR and PIS in 8 cadaveric specimens. The staged PSIA and IOTA enabled successful resection of both falcotentorial meningiomas with an uneventful postoperative course. In our anatomo-morphometrical study, superficial vermian veins at an average depth of 11.38 ± 1.5 mm and the superior vermian vein (SVV) at 54.13 ± 4.12 mm limited the access to the PIS during MSIA. MSIA required sacrifice of these veins and retraction of the vermian culmen of 20.88 ± 2.03 mm to obtain comparable operability indexes to PSIA and IOTA. Cerebellar and occipital lobe retraction averaged 14.31 ± 1.014 mm and 14.81 ± 1.17 mm during PSIA and IOTA respectively, which was significantly lower than during MSIA (p < 0.001). Only few minuscule veins were encountered along the access through PSIA and IOTA. The application of PSIA provided high operability scores around the pineal gland, ipsilateral colliculus and splenium, and acceptable scores on contralateral structures. The main advantage of IOTA was improving surgical maneuvers along the ipsilateral splenium. In summary, IOTA and PSIA may be advantageous in terms of brain retraction, vein sacrifice, and operability along the PR and PIS and can be effective for resection of complex falcotentorial meningiomas.

Load Distribution in the Lumbar Spine During Modeled Compression Depends on Lordosis.

Excessive or incorrect loading of lumbar spinal structures is commonly assumed as one of the factors to accelerate degenerative processes, which may lead to lower back pain. Accordingly, the mechanics of the spine under medical conditions, such as scoliosis or spondylolisthesis, is well-investigated. Treatments via both conventional therapy and surgical methods alike aim at restoring a "healthy" (or at least pain-free) load distribution. Yet, surprisingly little is known about the inter-subject variability of load bearings within a "healthy" lumbar spine. Hence, we utilized computer tomography data from 28 trauma-room patients, whose lumbar spines showed no visible sign of degeneration, to construct simplified multi-body simulation models. The subject-specific geometries, measured by the corresponding lumbar lordosis (LL) between the endplates of vertebra L1 and the sacrum, served as ceteris paribus condition in a standardized forward dynamic compression procedure. Further, the influence of stimulating muscles from the M. multifidus group was assessed. For the range of available LL from 28 to 66°, changes in compressive and shear forces, bending moments, as well as facet joint forces between adjacent vertebrae were calculated. While compressive forces tended to decrease with increasing LL, facet forces were tendentiously increasing. Shear forces decreased between more cranial vertebrae and increased between more caudal ones, while bending moments remained constant. Our results suggest that there exist significant, LL-dependent variations in the loading of "healthy" spinal structures, which should be considered when striving for individually appropriate therapeutic measures.

Comparison of Unruptured Intracranial Aneurysm Treatment Score and PHASES Score in Subarachnoid Hemorrhage Patients With Multiple Intracranial Aneurysms.

Objective: Unruptured Intracranial Aneurysm (UIA) Treatment Score (UIATS) and PHASES score are used to inform treatment decision making for UIAs (treatment or observation). We assessed the ability of the scoring systems to discriminate between ruptured aneurysms and UIAs in a subarachnoid hemorrhage (SAH) cohort with multiple aneurysms. Methods: We retrospectively applied PHASES and UIATS scoring to the aneurysms of 40 consecutive patients with SAH and multiple intracranial aneurysms. Results: PHASES score discriminated better between ruptured aneurysms and UIAs than UIATS. PHASES scores and the difference between the UIATS subscores were higher for ruptured aneurysms compared with UIAs, which reached significance for the PHASES score. PHASES score estimated a low 5-year rupture risk in a larger proportion of the UIAs (≤0.7% in 62.3%, ≤1.7% in 98.4%) than of the ruptured aneurysms (≤0.7% in 22.5%, ≤1.7% in 82.5%). In the 40 ruptured aneurysms, UIATS provided recommendation for treatment in 11 (27.5%), conservative management in 14 (35.0%), and was inconclusive in 15 cases (37.5%). In the 61 UIAs, UIATS recommended treatment in 16 (26.2%), conservative management in 29 (47.5%), and was inconclusive in 16 (26.2%) cases. Conclusion: Similar to previous SAH cohorts, a significant proportion of the ruptured aneurysms exhibited a low-rupture risk. Nevertheless, PHASES score discriminated between ruptured aneurysms and UIAs in our cohort; the lower discriminatory power of UIATS was due to high weights of aneurysm-independent factors. We recommend careful integration of the scores for individual decision making. Large-scale prospective trials are required to establish score-based treatment strategies for UIAs.

An age-dependent outcome analysis of microvascular decompression and percutaneous thermocoagulation in trigeminal neuralgia.

BACKGROUND: Trigeminal neuralgia (TN) is a severe pain condition and the most common facial neuralgia. While microvascular decompression (MVD) presents an excellent treatment in neurovascular compression cases, percutaneous thermocoagulation (PT) of the ganglion Gasseri is an alternative option. This study aimed to evaluate post-operative complication rate and outcome of both treatment strategies related to the patient's age. METHODS: The medical records of all patients with the diagnosis of trigeminal neuralgia undergoing an MVD or PT of the ganglion Gasseri (between January 2007 and September 2017) were reviewed to determine the efficacy and the complication rate of both methods in regard to the patient's age. RESULTS: Seventy-nine patients underwent MVD surgery and 39 a PT. The mean age of patients in the MVD group was 61 years and 73 years in the PT group. There were 59 (50%) female patients. Nerve-vessel conflict could be identified in 78 (98.7%) MVD and 17 (43.6%) PT patients on preoperative MRI. Charlson comorbidity index was significantly higher in PT group (2.4 (1.8) versus 3.8 (1.8) p < 0.001). The Barrow pain score (BPS) at the last follow-up demonstrated higher scores after PT (p = 0.007). The complication rate was markedly higher in PT group, mostly due to the facial hypesthesia (84.6% versus 27.8%; p < 0.001). Mean symptom-free survival was significantly shorter in the PT group (9 vs. 26 months, p < 0.001). It remained statistically significant when stratified into age groups: (65 years and older: 9 vs. 18 months, p = 0.001). Duration of symptoms (OR 1.005, 95% CI 1.000-1.010), primary procedure (OR 6.198, 95% CI 2.650-14.496), patient age (OR 1.033, 95% CI 1.002-1.066), and postoperative complication rate (OR 2.777, 95% CI 1.309-5.890) were associated with treatment failure. CONCLUSION: In this patient series, the MVD is confirmed to be an excellent treatment option independent of patient's age. However, while PT is an effective procedure, time to pain recurrence is shorter, and the favorable outcome (BPS 1 and 2) rate is lower compared to MVD. Hence MVD should be the preferred treatment and PT should remain an alternative in very selected cases when latter is not possible but not in the elderly patient per se.

Muscle-driven and torque-driven centrodes during modeled flexion of individual lumbar spines are disparate.

Lumbar spine biomechanics during the forward-bending of the upper body (flexion) are well investigated by both in vivo and in vitro experiments. In both cases, the experimentally observed relative motion of vertebral bodies can be used to calculate the instantaneous center of rotation (ICR). The timely evolution of the ICR, the centrode, is widely utilized for validating computer models and is thought to serve as a criterion for distinguishing healthy and degenerative motion patterns. While in vivo motion can be induced by physiological active structures (muscles), in vitro spinal segments have to be driven by external torque-applying equipment such as spine testers. It is implicitly assumed that muscle-driven and torque-driven centrodes are similar. Here, however, we show that centrodes qualitatively depend on the impetus. Distinction is achieved by introducing confidence regions (ellipses) that comprise centrodes of seven individual multi-body simulation models, performing flexion with and without preload. Muscle-driven centrodes were generally directed superior-anterior and tail-shaped, while torque-driven centrodes were located in a comparably narrow region close to the center of mass of the caudal vertebrae. We thus argue that centrodes resulting from different experimental conditions ought to be compared with caution. Finally, the applicability of our method regarding the analysis of clinical syndromes and the assessment of surgical methods is discussed.

Automated Grading of Cerebral Vasospasm to Standardize Computed Tomography Angiography Examinations After Subarachnoid Hemorrhage.

Background: Computed tomography angiography (CTA) is frequently used with computed tomography perfusion imaging (CTP) to evaluate whether endovascular vasospasm treatment is indicated for subarachnoid hemorrhage patients with delayed cerebral ischemia. However, objective parameters for CTA evaluation are lacking. In this study, we used an automated, investigator-independent, digital method to detect vasospasm, and we evaluated whether the method could predict the need for subsequent endovascular vasospasm treatment. Methods: We retrospectively reviewed the charts and analyzed imaging data for 40 consecutive patients with subarachnoid hemorrhages. The cerebrovascular trees were digitally reconstructed from CTA data, and vessel volume and the length of the arteries of the circle of Willis and their peripheral branches were determined. Receiver operating characteristic curve analysis based on a comparison with digital subtraction angiographies was used to determine volumetric thresholds that indicated severe vasospasm for each vessel segment. Results: The automated threshold-based volumetric evaluation of CTA data was able to detect severe vasospasm with high sensitivity and negative predictive value for predicting cerebral hypoperfusion on CTP, although the specificity and positive predictive value were low. Combining the automated detection of vasospasm on CTA and cerebral hypoperfusion on CTP was superior to CTP or CTA alone in predicting endovascular vasospasm treatment within 24 h after the examination. Conclusions: This digital volumetric analysis of the cerebrovascular tree allowed the objective, investigator-independent detection and quantification of vasospasms. This method could be used to standardize diagnostics and the selection of subarachnoid hemorrhage patients with delayed cerebral ischemia for endovascular diagnostics and possible interventions.

Multicolor 3D Printing of Complex Intracranial Tumors in Neurosurgery.

Three-dimensional (3D) printing technologies offer the possibility of visualizing patient-specific pathologies in a physical model of correct dimensions. The model can be used for planning and simulating critical steps of a surgical approach. Therefore, it is important that anatomical structures such as blood vessels inside a tumor can be printed to be colored not only on their surface, but throughout their whole volume. During simulation this allows for the removal of certain parts (e.g., with a high-speed drill) and revealing internally located structures of a different color. Thus, diagnostic information from various imaging modalities (e.g., CT, MRI) can be combined in a single compact and tangible object. However, preparation and printing of such a fully colored anatomical model remains a difficult task. Therefore, a step-by-step guide is provided, demonstrating the fusion of different cross-sectional imaging data sets, segmentation of anatomical structures, and creation of a virtual model. In a second step the virtual model is printed with volumetrically colored anatomical structures using a plaster-based color 3D binder jetting technique. This method allows highly accurate reproduction of patient-specific anatomy as shown in a series of 3D-printed petrous apex chondrosarcomas. Furthermore, the models created can be cut and drilled, revealing internal structures that allow for simulation of surgical procedures.

Image-Guided Transcranial Doppler Ultrasound for Monitoring Posthemorrhagic Vasospasms of Infratentorial Arteries: A Feasibility Study.

BACKGROUND: A considerable number of patients with subarachnoid hemorrhage (SAH) develop vasospasms of the infratentorial arteries. Transcranial Doppler sonography (TCD) is used to screen for vasospasm. In this study, we used a technical modification that combines TCD with an image guidance device that the operator can use to navigate to the ultrasonic window and to predefined intracranial vascular targets. Our aim was to analyze the feasibility, spatial precision, and spatial reproducibility of serial image-guided TCD of infratentorial and-for comparison-supratentorial arteries in the clinical setting of monitoring for vasospasm after SAH. METHODS: The study included 10 SAH patients, who each received 5 serial image-guided TCD examinations. Using computed tomography angiography data, trajectories to the infratentorial and supratentorial cerebral arteries were planned and loaded into an image guidance device tracking the Doppler probe. As a measure of spatial precision and spatial reproducibility, we analyzed the distances between the positions of preplanned vascular targets and optimal Doppler signals. RESULTS: The mean distance between preplanned and optimal target points was 4.8 ± 2.1 mm (first exam), indicating high spatial precision. The spatial precision decreased with increasing depth of the vascular target. In all patients, image-guided TCD detected all predefined supratentorial and infratentorial vascular segments. There were no significant changes in spatial precision in serial exams, indicating high reproducibility. CONCLUSIONS: Image-guided TCD is feasible for supratentorial and infratentorial arteries. It shows high spatial precision and reproducibility. This study provides a basis for future clinical studies on image-guided TCD for post-SAH vasospasm screening.

Neutrophils mediate early cerebral cortical hypoperfusion in a murine model of subarachnoid haemorrhage.

Cerebral hypoperfusion in the first hours after subarachnoid haemorrhage (SAH) is a major determinant of poor neurological outcome. However, the underlying pathophysiology is only partly understood. Here we induced neutropenia in C57BL/6N mice by anti-Ly6G antibody injection, induced SAH by endovascular filament perforation, and analysed cerebral cortical perfusion with laser SPECKLE contrast imaging to investigate the role of neutrophils in mediating cerebral hypoperfusion during the first 24 h post-SAH. SAH induction significantly increased the intracranial pressure (ICP), and significantly reduced the cerebral perfusion pressure (CPP). At 3 h after SAH, ICP had returned to baseline and CPP was similar between SAH and sham mice. However, in SAH mice with normal neutrophil counts cortical hypoperfusion persisted. Conversely, despite similar CPP, cortical perfusion was significantly higher at 3 h after SAH in mice with neutropenia. The levels of 8-iso-prostaglandin-F2α in the subarachnoid haematoma increased significantly at 3 h after SAH in animals with normal neutrophil counts indicating oxidative stress, which was not the case in neutropenic SAH animals. These results suggest that neutrophils are important mediators of cortical hypoperfusion and oxidative stress early after SAH. Targeting neutrophil function and neutrophil-induced oxidative stress could be a promising new approach to mitigate cerebral hypoperfusion early after SAH.

Doppler sonography enhances rtPA-induced fibrinolysis in an in vitro clot model of spontaneous intracerebral hemorrhages.

BACKGROUND: Transcranial Doppler (TCD) was shown to enhance intravascular fibrinolysis by rtPA in ischemic stroke. Studies revealed that catheter-based administration of rtPA induces lysis of intracerebral hemorrhages (ICH). However, it is unknown whether TCD would be suitable to enhance rtPA-induced fibrinolysis in patients with ICH. The aim of this study was to assess the potential of TCD to enhance rtPA-induced fibrinolysis in an in vitro clot system. METHODS: Reproducible human blood clots of 25 ml were incubated in a water bath at 37°C during treatments. They were weighed before and after 6 different treatments: (I) control (incubation only), (II) rtPA only, (III) one Doppler probe, (IV) two Doppler probes placed vis-à-vis, (V) one probe and rtPA and (VI) two probes and rtPA. To quantify lysis of the blood clots and attenuation of the Doppler through a temporal squama acoustic peak rarefaction pressure (APRP) was measured in the field of the probes. Temperature was assessed to evaluate possible side effects. RESULTS: Clot weight was reduced in all groups. The control group had the highest relative end weight of 70.2%±7.2% compared to all other groups (p<0,0001). Most efficient lysis was achieved using (VI) 2 probes and rtPA 36.3%±4.4% compared to (II, III, IV) (p<0.0001; p = 0.0002; p = 0.048). APRP was above lysis threshold (535.5±7.2 kPa) using 2 probes even through the temporal squama (731.6±32.5 kPa) (p = 0.0043). There was a maximal temperature elevation of 0.17±0.07°C using both probes. CONCLUSIONS: TCD significantly enhances rtPA-induced lysis of blood clots, and the effect is amplified by using multiple probes. Our results indicate that bitemporal TCD insonation of hematomas could be a new and safe approach to enhance fibrinolysis of ICH´s treated with intralesional catheter and rtPA.

Volumetric analysis of intracranial vessels: a novel tool for evaluation of cerebral vasospasm.

PURPOSE: Together with other diagnostic modalities, computed tomography angiography (CTA) is commonly used to indicate endovascular vasospasm treatment after subarachnoid hemorrhage (SAH), despite the fact that objective, user-independent parameters for evaluation of CTA are lacking. This exploratory study was designed to investigate whether quantification of vasospasm by automated volumetric analysis of the middle cerebral artery M1 segment from CTA data could be used as an objective parameter to indicate endovascular vasospasm treatment. METHODS: We retrospectively identified SAH patients who underwent transcranial Doppler sonography (TCD), CTA, and CT perfusion (CTP), with or without subsequent endovascular treatment. We determined vessel volume/vessel length of the M1 segments from CTA data and used receiver operating characteristic curve analysis to determine the optimal threshold of vessel volume to predict vasospasm requiring endovascular treatment. In addition, blinded investigators independently analyzed TCD, CTA, and CTP data. RESULTS: Of 45 CTA examinations with corresponding CTP and TCD examinations (24 SAH patients), nine indicated the need for endovascular vasospasm treatment during examination. In our patients, vessel volume < 5.8 µL/mm was moderately sensitive but fairly specific to detect vasospasm requiring endovascular treatment (sensitivity, 67%; specificity, 78%; negative predictive value (NPV), 89%; positive predictive value (PPV), 46%). For CTA, CTP, and TCD, we found NPVs of 96%, 92%, and 89%, PPVs of 40%, 35%, and 35%, sensitivities of 89%, 78%, and 67%, and specificities of 67%, 64%, and 69%, respectively. CONCLUSION: Vessel volumes could provide a new objective parameter for the interpretation of CTA data and could thereby improve multimodal assessment of vasospasm in SAH patients.

Re-purposing Chloroquine for Glioblastoma: Potential Merits and Confounding Variables.

There is a growing evidence that antimalarial chloroquine could be re-purposed for cancer treatment. A dozen of clinical trials have been initiated within the past 10 years to test the potential of chloroquine as an adjuvant treatment for therapy-refractory cancers including glioblastoma, one of the most aggressive human cancers. While there is considerable evidence for the efficacy and safety of chloroquine the mechanisms underlying the tumor suppressive actions of this drug remain elusive. Up until recently, inhibition of the late stage of autophagy was thought to be the major mechanism of chloroquine-mediated cancer cells death. However, recent research provided compelling evidence that autophagy-inhibiting activities of chloroquine are dispensable for its ability to suppress tumor cells growth. These unexpected findings necessitate a further elucidation of the molecular mechanisms that are essential for anti-cancer activities of CHQ. This review discusses the versatile actions of chloroquine in cancer cells with particular focus on glioma cells.

A Volumetric Method for Quantification of Cerebral Vasospasm in a Murine Model of Subarachnoid Hemorrhage.

Subarachnoid hemorrhage (SAH) is a subtype of hemorrhagic stroke. Cerebral vasospasm that occurs in the aftermath of the bleeding is an important factor determining patient outcome and is therefore frequently taken as a study endpoint. However, in small animal studies on SAH, quantification of cerebral vasospasm is a major challenge. Here, an ex vivo method is presented that allows quantification of volumes of entire vessel segments, which can be used as an objective measure to quantify cerebral vasospasm. In a first step, endovascular casting of the cerebral vasculature is performed using a radiopaque casting agent. Then, cross-sectional imaging data are acquired by micro computed tomography. The final step involves 3-dimensional reconstruction of the virtual vascular tree, followed by an algorithm to calculate center lines and volumes of the selected vessel segments. The method resulted in a highly accurate virtual reconstruction of the cerebrovascular tree shown by a diameter-based comparison of anatomical samples with their virtual reconstructions. Compared with vessel diameters alone, the vessel volumes highlight the differences between vasospastic and non-vasospastic vessels shown in a series of SAH and sham-operated mice.

Correction: Combination of ultrasound and rtPA enhances fibrinolysis in an In Vitro clot system.

[This corrects the article DOI: 10.1371/journal.pone.0188131.].

Combination of ultrasound and rtPA enhances fibrinolysis in an In Vitro clot system.

BACKGROUND: Catheter-based lysis with recombinant tissue plasminogen activator (rtPA) is a well-established therapy for spontaneous intracerebral hemorrhage (ICH). The effectiveness of this therapy can be increased with ultrasound, but the optimal conditions are not yet clearly established. Using a novel in vitro system of blood clots previously developed by our group, we investigated various parameters of intralesional sonothrombolysis using an endosonography catheter in combination with rtPA. METHODS: Standardized human blood clots were equipped with a drainage catheter and weighed before and after 4 treatments: control (drainage only), rtPA only, ultrasound only and the combination of rtPA+ultrasound. The effectiveness of ultrasound was further analysed in terms of optimal frequency, duration and distance to the probe. Temperature and acoustic peak rarefaction pressure (APRP) were assessed to analyse potential adverse effects and quantify lysis. Histo-morphological analysis of the treated clots was performed by H&E staining and confocal laser scanning microscopy using fluorescent fibrinogen. RESULTS: The combined treatment rtPA+ultrasound achieved the highest lysis rates with a relative weight of 30.3%±5.5% (p≤0.0001) compared to all other groups. Similar results were observed when treating aged clots. Confocal fluorescent microscopy of the treated clots revealed a rarefied fibrin mesh without cavitations. No relevant temperature increase occurred (0.53±0.75°C). The optimal insonation treatment time was 1 hour. APRP measurements showed a lysis threshold of 515.5±113.4 kPa. Application of 10 MHz achieved optimal lysis and lysis radius, while simultaneously proving to be the best frequency for morphologic imaging of the clot and surrounding tissue. CONCLUSIONS: These promising data provide the basis for an individualized minimal invasive ICH therapy by rtPA and sonothrombolysis independent of ICH age.

Three-dimensional Cross-Platform Planning for Complex Spinal Procedures: A New Method Adaptive to Different Navigation Systems.

STUDY DESIGN: A feasibility study. OBJECTIVE: To develop a method based on the DICOM standard which transfers complex 3-dimensional (3D) trajectories and objects from external planning software to any navigation system for planning and intraoperative guidance of complex spinal procedures. SUMMARY OF BACKGROUND DATA: There have been many reports about navigation systems with embedded planning solutions but only few on how to transfer planning data generated in external software. MATERIALS AND METHODS: Patients computerized tomography and/or magnetic resonance volume data sets of the affected spinal segments were imported to Amira software, reconstructed to 3D images and fused with magnetic resonance data for soft-tissue visualization, resulting in a virtual patient model. Objects needed for surgical plans or surgical procedures such as trajectories, implants or surgical instruments were either digitally constructed or computerized tomography scanned and virtually positioned within the 3D model as required. As crucial step of this method these objects were fused with the patient's original diagnostic image data, resulting in a single DICOM sequence, containing all preplanned information necessary for the operation. By this step it was possible to import complex surgical plans into any navigation system. RESULTS: We applied this method not only to intraoperatively adjustable implants and objects under experimental settings, but also planned and successfully performed surgical procedures, such as the percutaneous lateral approach to the lumbar spine following preplanned trajectories and a thoracic tumor resection including intervertebral body replacement using an optical navigation system. To demonstrate the versatility and compatibility of the method with an entirely different navigation system, virtually preplanned lumbar transpedicular screw placement was performed with a robotic guidance system. CONCLUSIONS: The presented method not only allows virtual planning of complex surgical procedures, but to export objects and surgical plans to any navigation or guidance system able to read DICOM data sets, expanding the possibilities of embedded planning software.

Evaluation of robot-guided minimally invasive implantation of 2067 pedicle screws.

Objective Recent studies have investigated the role of spinal image guidance for pedicle screw placement. Many authors have observed an elevated placement accuracy and overall improvement of outcome measures. This study assessed a bi-institutional experience following introduction of the Renaissance miniature robot for spinal image guidance in Europe. Methods The medical records and radiographs of all patients who underwent robot-guided implantation of spinal instrumentation using the novel system (between October 2011 and March 2015 in Mainz and February 2014 and February 2016 in Regensburg) were reviewed to determine the efficacy and safety of the newly introduced robotic system. Screw position accuracy, complications, exposure durations to intraoperative radiation, and reoperation rate were assessed. Results Of the 413 surgeries that used robotic guidance, 406 were via a minimally invasive approach. In 7 cases the surgeon switched to conventional screw placement, using a midline approach, due to referencing problems. A total of 2067 screws were implanted using robotic guidance, and 1857 screws were evaluated by postoperative CT. Of the 1857 screws, 1799 (96.9%) were classified as having an acceptable or good position, whereas 38 screws (2%) showed deviations of 3-6 mm and 20 screws (1.1%) had deviations > 6 mm. Nine misplaced screws, implanted in 7 patients, required revision surgery, yielding a screw revision rate of 0.48% of the screws and 7 of 406 (1.7%) of the patients. The mean ± SD per-patient intraoperative fluoroscopy exposure was 114.4 (± 72.5) seconds for 5.1 screws on average and any further procedure required. Perioperative and direct postoperative complications included hemorrhage (2 patients, 0.49%) and wound infections necessitating surgical revision (20 patients, 4.9%). Conclusions The hexapod miniature robotic device proved to be a safe and robust instrument in all situations, including those in which patients were treated on an emergency basis. Placement accuracy was high; peri- and early postoperative complication rates were found to be lower than rates published in other series of percutaneous screw placement techniques. Intraoperative radiation exposure was found to be comparable to published values for other minimally invasive and conventional approaches.

A segmentation-based volumetric approach to localize and quantify cerebral vasospasm based on tomographic imaging data.

INTRODUCTION: Quantification of cerebral vasospasm after subarachnoid hemorrhage (SAH) is crucial in animal studies as well as clinical routine. We have developed a method for computer-based volumetric assessment of intracranial blood vessels from cross-sectional imaging data. Here we demonstrate the quantification of vasospasm from micro computed tomography (micro-CT) data in a rodent SAH model and the transferability of the volumetric approach to clinical data. METHODS: We obtained rodent data by performing an ex vivo micro-CT of murine brains after sham surgery or SAH by endovascular filament perforation on day 3 post hemorrhage. Clinical CT angiography (CTA) was performed for diagnostic reasons unrelated to this study. We digitally reconstructed and segmented intracranial vascular trees, followed by calculating volumes of defined vessel segments by standardized protocols using Amira® software. RESULTS: SAH animals demonstrated significantly smaller vessel diameters compared with sham (MCA: 134.4±26.9µm vs.165.0±18.7µm, p<0.05). We could highlight this difference by analyzing vessel volumes of a defined MCA-ICA segment (SAH: 0.044±0.017µl vs. sham: 0.07±0.006µl, p<0.001). Analysis of clinical CTA data allowed us to detect and volumetrically quantify vasospasm in a series of 5 SAH patients. Vessel diameters from digital reconstructions correlated well with those measured microscopically (rodent data, correlation coefficient 0.8, p<0.001), or angiographically (clinical data, 0.9, p<0.001). CONCLUSIONS: Our methodological approach provides accurate anatomical reconstructions of intracranial vessels from cross-sectional imaging data. It allows volumetric assessment of entire vessel segments, hereby highlighting vasospasm-induced changes objectively in a murine SAH model. This method could also be a helpful tool for analysis of clinical CTA.