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BACKGROUND: In patients with aneurysmal subarachnoid haemorrhage, short-term antifibrinolytic therapy with tranexamic acid has been shown to reduce the risk of rebleeding. However, whether this treatment improves clinical outcome is unclear. We investigated whether ultra-early, short-term treatment with tranexamic acid improves clinical outcome at 6 months.METHODS: In this multicentre prospective, randomised, controlled, open-label trial with masked outcome assessment, adult patients with spontaneous CT-proven subarachnoid haemorrhage in eight treatment centres and 16 referring hospitals in the Netherlands were randomly assigned to treatment with tranexamic acid in addition to care as usual (tranexamic acid group) or care as usual only (control group). Tranexamic acid was started immediately after diagnosis in the presenting hospital (1 g bolus, followed by continuous infusion of 1 g every 8 h, terminated immediately before aneurysm treatment, or 24 h after start of the medication, whichever came first). The primary endpoint was clinical outcome at 6 months, assessed by the modified Rankin Scale, dichotomised into a good (0-3) or poor (4-6) clinical outcome. Both primary and safety analyses were according to intention to treat. This trial is registered at ClinicalTrials.gov, NCT02684812.FINDINGS: Between July 24, 2013, and July 29, 2019, we enrolled 955 patients; 480 patients were randomly assigned to tranexamic acid and 475 patients to the control group. In the intention-to-treat analysis, good clinical outcome was observed in 287 (60%) of 475 patients in the tranexamic acid group, and 300 (64%) of 470 patients in the control group (treatment centre adjusted odds ratio 0·86, 95% CI 0·66-1·12). Rebleeding after randomisation and before aneurysm treatment occurred in 49 (10%) patients in the tranexamic acid and in 66 (14%) patients in the control group (odds ratio 0·71, 95% CI 0·48-1·04). Other serious adverse events were comparable between groups.INTERPRETATION: In patients with CT-proven subarachnoid haemorrhage, presumably caused by a ruptured aneurysm, ultra-early, short-term tranexamic acid treatment did not improve clinical outcome at 6 months, as measured by the modified Rankin Scale.FUNDING: Fonds NutsOhra.

Background and ObjectivesThe ULTRA trial showed that ultra-early and short-term tranexamic acid treatment after subarachnoid hemorrhage did not improve clinical outcome at 6 months. An expected proportion of the included patients experienced nonaneurysmal subarachnoid hemorrhage. In this post hoc study, we will investigate whether ultra-early and short-term tranexamic acid treatment in patients with aneurysmal subarachnoid hemorrhage improves clinical outcome at 6 months.MethodsThe ULTRA trial is a multicenter, prospective, randomized, controlled, open-label trial with blinded outcome assessment, conducted between July 24, 2013, and January 20, 2020. After confirmation of subarachnoid hemorrhage on noncontrast CT, patients were allocated to either ultra-early and short-term tranexamic acid treatment with usual care or usual care only. In this post hoc analysis, we included all ULTRA participants with a confirmed aneurysm on CT angiography and/or digital subtraction angiography. The primary endpoint was clinical outcome at 6 months, assessed by the modified Rankin scale (mRS), dichotomized into good (0–3) and poor (4–6) outcomes.ResultsOf the 813 ULTRA trial patients who experienced an aneurysmal subarachnoid hemorrhage, 409 (50%) were assigned to the tranexamic acid group and 404 (50%) to the control group. In the intention-to-treat analysis, 233 of 405 (58%) patients in the tranexamic acid group and 238 of 399 (60%) patients in the control group had a good clinical outcome (adjusted odds ratio [aOR] 0.92; 95% CI 0.69–1.24). None of the secondary outcomes showed significant differences between the treatment groups: excellent clinical outcome (mRS 0–2) (aOR 0.76; 95% CI 0.57–1.03), all-cause mortality at 30 days (aOR 0.91; 95% CI 0.65–1.28), and all-cause mortality at 6 months (aOR 1.10; 95% CI 0.80–1.52).DiscussionUltra-early and short-term tranexamic acid treatment did not improve clinical outcomes at 6 months in patients with aneurysmal subarachnoid hemorrhage and therefore cannot be recommended.Trial Registration InformationClinicalTrials.gov(NCT02684812; submission date February 18, 2016, first patient enrollment on July 24, 2013).Classification of EvidenceThis study provides Class II evidence that tranexamic acid does not improve outcomes in patients presenting with aneurysmal subarachnoid hemorrhage.

Background Surgical treatment of intracranial saccular aneurysms aims to prevent (re)hemorrhage by complete occlusion of the aneurysmal lumen. It is unclear whether routine postoperative imaging, to assess aneurysmal occlusion, is necessary since intraoperative assessment by the neurosurgeon may be sufficient. We assessed routine clinical protocols for post-clipping imaging in the Netherlands and determined whether intraoperative assessment of aneurysm clippings sufficiently predicts aneurysm residuals. Methods A survey was conducted to assess postoperative imaging protocols in centers performing clipping of intracranial aneurysms in the Netherlands (n = 9). Furthermore, a retrospective single-center cohort study was performed to determine the predictive value of intraoperative assessment of aneurysm occlusion in relation to postoperative digital subtraction angiography (DSA) findings, between 2009 and 2017. Results No center performed intraoperative DSA in a hybrid OR, routinely. Respectively, four (44.4%), seven (77.8%), and three (33.3%) centers did not routinely perform early postoperative imaging, late follow-up imaging, or any routine imaging at all. Regarding our retrospective study, 106 patients with 132 clipped aneurysms were included. There were 23 residuals ≥ 1 mm (17.4%), of which 10 (43.5%) were unexpected. For the presence of these residuals, intraoperative assessment showed a sensitivity of 56.5%, a specificity of 86.2%, a positive predictive value of 46.4%, and a negative predictive value of 90.4%. Conclusions There is lack of consensus regarding the post-clipping imaging strategy in the Netherlands. Since intraoperative assessment is shown to be insufficient to predict postoperative aneurysm residuals, we advocate routine postoperative imaging after aneurysm clipping unless this is not warranted on the basis of patient age, clinical condition, and/or comorbidity.

Object In the past, the accuracy of surface matching has been shown to be disappointing. We aimed to determine whether this had improved over the years by assessing application accuracy of current navigation systems, using either surface matching or point-pair matching. Methods Eleven patients, scheduled for intracranial surgery, were included in this study after a power analysis had shown this small number to be sufficient. Prior to surgery, one additional fiducial marker was placed on the scalp, the “target marker,” where the entry point of surgery was to be expected. Using one of three different navigation systems, two patient-to-image registration procedures were performed: one based on surface matching and one based on point-pair matching. Each registration procedure was followed by the digitization of the target marker’s location, allowing calculation of the target registration error. If the system offered surface matching improvement, this was always used; and for the two systems that routinely offer an estimate of neuronavigation accuracy, this was also recorded. Results The error in localizing the target marker using point-pair matching or surface matching was respectively 2.49 mm and 5.35 mm, on average (p

BACKGROUND AND PURPOSE: 4D CT angiography is increasingly used in clinical practice for the assessment of different neurovascular disorders. Optimized processing of 4D-CTA is crucial for diagnostic interpretation because of the large amount of data that is generated. A color-mapping method for 4D-CTA is presented for improved and enhanced visualization of the cerebral vasculature hemodynamics. This method was applied to detect cranial AVFs. MATERIALS AND METHODS: All patients who underwent both 4D-CTA and DSA in our hospital from 2011 to 2018 for the clinical suspicion of a cranial AVF or carotid cavernous fistula were retrospectively collected. Temporal information in the cerebral vasculature was visualized using a patient-specific color scale. All color-maps were evaluated by 3 observers for the presence or absence of an AVF or carotid cavernous fistula. The presence or absence of cortical venous reflux was evaluated as a secondary outcome measure. RESULTS: In total, 31 patients were included, 21 patients with and 10 without an AVF. Arterialization of venous structures in AVFs was accurately visualized using color-mapping. There was high sensitivity (86%–100%) and moderate-to-high specificity (70%–100%) for the detection of AVFs on color-mapping 4D-CTA, even without the availability of dynamic subtraction rendering. The diagnostic performance of the 3 observers in the detection of cortical venous reflux was variable (sensitivity, 43%–88%; specificity, 60%–80%). CONCLUSIONS: Arterialization of venous structures can be visualized using color-mapping of 4D-CTA and proves to be accurate for the detection of cranial AVFs. This finding makes color-mapping a promising visualization technique for assessing temporal hemodynamics in 4D-CTA.

Item does not contain fulltext OBJECTIVES: Finding the underlying cause for pulsatile tinnitus can be challenging. We aimed to determine the incidence of arteriovenous shunts, i.e., arteriovenous malformations (AVMs) or dural arteriovenous fistulas (dAVFs), in patients referred for catheter angiography (digital subtraction angiography [DSA]). Furthermore, we assessed which clinical features were predictive for the presence of such a lesion. STUDY DESIGN AND METHODS: Fifty-one patients with pulsatile tinnitus, who were referred to us for DSA to exclude an arteriovenous shunt, were enrolled, prospectively. MAIN OUTCOME MEASURES: DSA determined the presence of a dAVF or AVM. Clinical characteristics were recorded systematically and all patients underwent a physical examination. RESULTS: Fifty patients were included in the final analyses. While no AVMs were found, a dAVF was found in 12 cases (24%). Three of these demonstrated cortical venous reflux, thus requiring treatment due to the risk of hemorrhage. In three cases (6%), DSA demonstrated a non-arteriovenous-shunt abnormality, likely causing the tinnitus. The odds of having a dAVF were significantly raised by unilaterality, objective bruit, and the ability to influence the tinnitus with compression. Unilaterality even had a negative predictive value of 1 and, if used as selection criterion, would have raised dAVF prevalence from 24 to 32%. CONCLUSION: In a tertiary care setting, the prevalence of dAVFs in patients with pulsatile tinnitus is not negligible. Thus, patients with unilateral pulsatile tinnitus should be offered dynamic vascular imaging to rule out a dAVF. Especially, since some of these patients are at risk of intracranial hemorrhage and treatment options exist.

Contains fulltext : 200084.pdf (Publisher’s version ) (Open Access) The historical developments of endovascular neurosurgery in the Netherlands are described.

Background: Guidelines on the management of aneurysmal subarachnoid hemorrhage (aSAH) recommend euvolemia, whereas hypervolemia may cause harm. We investigated whether high early fluid input is associated with delayed cerebral ischemia (DCI), and if fluid input can be safely decreased using transpulmonary thermodilution (TPT). Methods: We retrospectively included aSAH patients treated at an academic intensive care unit (2007-2011; cohort 1) or managed with TPT (2011-2013; cohort 2). Local guidelines recommended fluid input of 3 L daily. More fluids were administered when daily fluid balance fell below +500 mL. In cohort 2, fluid input in high-risk patients was guided by cardiac output measured by TPT per a strict protocol. Associations of fluid input and balance with DCI were analyzed with multivariable logistic regression (cohort 1), and changes in hemodynamic indices after institution of TPT assessed with linear mixed models (cohort 2). Results: Cumulative fluid input 0 to 72 hours after admission was associated with DCI in cohort 1 (n=223; odds ratio [OR] 1.19/L; 95% confidence interval 1.07-1.32), whereas cumulative fluid balance was not. In cohort 2 (23 patients), using TPT fluid input could be decreased from 6.0 ± 1.0 L before to 3.4 ± 0.3 L; P = .012), while preload parameters and consciousness remained stable. Conclusion: High early fluid input was associated with DCI. Invasive hemodynamic monitoring was feasible to reduce fluid input while maintaining preload. These results indicate that fluid loading beyond a normal preload occurs, may increase DCI risk, and can be minimized with TPT.

Background and objective One of the treatment options for arteriovenous malformations consists of embolization, with a choice of various embolic agents, with or without subsequent surgical excision. If embolization is offered without subsequent surgery, the embolic material will stay in situ, in which case the consistency and color become important in superficial lesions. The purpose of this case report is to describe if the use of a novel liquid embolic agent (PHIL) is well suited for treatment of superficial AVMs without subsequent surgery. Case description A 30-year-old male presented with a painful reddish, pulsatile swelling of the left ear that had been present for more than 10 years. Angiography confirmed an arteriovenous malformation supplied by the superficial temporal artery and the posterior auricular artery. The lesion was successfully treated by embolization with PHIL, through the superficial temporal artery. A minute residual shunt, from the posterior auricular artery, was accepted. Immediate disappearance of pulsatile tinnitus was reported. Moreover, return of normal skin color was observed without discomfort from the embolic deposits. This result has been stable throughout one year of clinical follow-up. Conclusion To our knowledge, this is the first case report describing PHIL embolization as a treatment option for superficial arteriovenous malformations without the necessity for subsequent surgery. The white color and rubbery consistency are beneficial characteristics of PHIL in treatment of subcutaneous lesions, especially in cosmetically relevant locations.

OBJECTIVE During image-guided neurosurgery, if the surgeon is not fully orientated to the surgical position, he or she will briefly shift attention toward the visualization interface of an image guidance station, receiving only momentary "point-in-space" information. The aim of this study was to develop a novel visual interface for neuronavigation during brain tumor surgery, enabling intraoperative feedback on the entire progress of surgery relative to the anatomy of the brain and its pathology, regardless of the interval at which the surgeon chooses to look. METHODS New software written in Java (Sun Microsystems, Inc., Santa Clara, CA) was developed to visualize the cumulative recorded instrument positions intraoperatively. This allowed surgeons to see all previous instrument positions during the elapsed surgery. This new interactive interface was then used in 17 frameless image-guided neurosurgical procedures. The purpose of the first 11 cases was to obtain clinical experience with this new interface. In these cases, workflow and volumetric feedback (WVF) were available at the surgeons' discretion (Protocol A). In the next 6 cases, WVF was provided only after a complete resection was claimed (Protocol B). RESULTS With the novel interactive interface, dynamics of surgical resection, displacement of cortical anatomy, and digitized functional data could be visualized intraoperatively. In the first group (Protocol A), surgeons expressed the view that WVF had affected their decision making and aided resection (10 of 11 cases). In 3 of 6 cases in the second group (Protocol B), tumor resections were extended after evaluation of WVF. By digitizing the cortical surface, an impression of the cortical shift could be acquired in all 17 cases. The maximal cortical shift measured 20 mm, but it typically varied between 0 and 10 mm. CONCLUSION Our first clinical results suggest that the embedding of WVF contributes to improvement of surgical awareness and tumor resection in image-guided neurosurgery in a swift and simple manner.

In this study the authors measured the effect of auditory feedback during image-guided surgery (IGS) in a phantom model and in a clinical setting. In the phantom setup, advanced IGS with complementary auditory feedback was compared with results obtained with 2 routine forms of IGS, either with an on-screen image display or with imageinjection via a microscope. The effect was measured by means of volumetric resection assessments. The authors also present their first clinical data concerning the effects of complementary auditory feedback on instrument handling during image-guided neurosurgery. When using image-injection through the microscope for navigation, however, resection quality was significantly worse. In the clinical portion of the study, the authors performed resections of cerebral mass lesions in 6 patients with the aid of auditory feedback. Instrument tip speeds were slightly (although significantly) influenced by this feedback during resection. Overall, the participating neurosurgeons reported that the auditory feedback helped in decision-making during resection without negatively influencing instrument use. Postoperative volumetric imaging studies revealed resection rates of ≥ 95% when IGS with auditory feedback was used. There was only a minor amount of brain shift, and postoperative resection volumes corresponded well with the preoperative intentions of the neurosurgeon. Although the results of phantom surgery with auditory feedback revealed no significant effect on resection quality or extent, auditory cues may help prevent damage to eloquent brain structures.

Object The aim of this study was to compare three patient-to-image registration methods in frameless stereotaxy in terms of their application accuracy (the accuracy with which the position of a target can be determined intraoperatively). In frameless stereotaxy, imaging information is transposed to the surgical field to show the spatial position of a localizer or surgical instrument. The mathematical relationship between the image volume and the surgical working space is calculated using a rigid body transformation algorithm, based on point-pair matching or surface matching. Methods Fifty patients who were scheduled to undergo a frameless image-guided neurosurgical procedure were included in the study. Prior to surgery, the patients underwent either computerized tomography (CT) scanning or magnetic resonance (MR) imaging with widely distributed adhesive fiducial markers on the scalp. An extra fiducial marker was placed on the head as a target, as near as possible to the intracranial lesion. Prior to each surgical procedure, an optical tracking system was used to perform three separate patient-to-image registration procedures, using anatomical landmarks, adhesive markers, or surface matching. Subsequent to each registration, the target registration error (TRE), defined as the Euclidean distance between the image space coordinates and world space coordinates of the target marker, was determined. Independent of target location or imaging modality, mean application accuracy (± standard deviation) was 2.49 ± 1.07 mm when using adhesive markers. Using the other two registration strategies, mean TREs were significantly larger (surface matching, 5.03 ± 2.30 mm; anatomical landmarks, 4.97 ± 2.29 mm; p < 0.001 for both). Conclusions The results of this study show that skin adhesive fiducial marker registration is the most accurate noninvasive registration method. When images from an earlier study are to be used and accuracy may be slightly compromised, anatomical landmarks and surface matching are equally accurate alternatives.

OBJECTIVE In this clinical study, we quantify intra- and interobserver variability of manual fiducial localization in image space, as the effect of repetitive manual fiducial localization is still unclear, especially on a target position. METHODS After uploading eight imaging datasets with a total of 56 skin adhesive fiducial markers in a commercially available image-guidance system, the centroids of the fiducial markers were tagged. This task was executed repeatedly at three separate moments by six different observers. The fiducial localization variability and its target shift effect in image space were determined out of 1008 tagged fiducial markers. RESULTS The maximal intraobserver target shift effect measured 0.72 +/- 0.14 mm in computed tomographic image space and 0.95 +/- 0.21 mm in magnetic resonance image space. CONCLUSION If a fiducial tagging task is well understood, repetitive manual detection of fiducial markers can be done with a low intraobserver fiducial localization variability, resulting in a submillimetric effect on a target position, either in computed tomographic or magnetic resonance image space. Therefore, we think it is justified to determine the centroids of a skin adhesive fiducial marker in the image space by hand.

Obsessive-compulsive disorder (OCD) is a chronic, disabling disorder. Psychosurgery may be indicated for a subset of patients for whom no conventional treatment is satisfactory. This paper focuses on the stereotactic subcaudate tractotomy (SST). Thus far, these procedures have been carried out using frame-based stereotactic techniques. However, modern - highly accurate - frameless stereotactic procedures have successfully been introduced in neurosurgical practice. We developed a novel frameless stereotactic subcaudate tractotomy procedure with promising initial results in a patient suffering from intractable OCD. This is the first report on frameless SST. Future studies should examine whether other ablative stereotactic psychosurgery procedures can be done using frameless stereotactic methods.

Background and Purposes. The 320-detector row CT scanner enables visualization of whole-brain hemodynamic information (dynamic CT angiography (CTA) derived from CT perfusion scans). However, arterial image quality in dynamic CTA (dCTA) is inferior to arterial image quality in standard CTA. This study evaluates whether the arterial image quality can be improved by using a total bolus extraction (ToBE) method.Materials and Methods. DCTAs of 15 patients, who presented with signs of acute cerebral ischemia, were derived from 320-slice CT perfusion scans using both the standard subtraction method and the proposed ToBE method. Two neurointerventionalists blinded to the scan type scored the arterial image quality on a 5-point scale in the 4D dCTAs in consensus. Arteries were divided into four categories: (I) large extradural, (II) intradural (large, medium, and small), (III) communicating arteries, and (IV) cerebellar and ophthalmic arteries.Results. Quality of extradural and intradural arteries was significantly higher in the ToBE dCTAs than in the standard dCTAs (extraduralP=0.001, large intraduralP<0.001, medium intraduralP<0.001, and small intraduralP<0.001).Conclusion. The 4D dCTAs derived with the total bolus extraction (ToBE) method provide hemodynamic information combined with improved arterial image quality as compared to standard 4D dCTAs.

Obsessive-compulsive disorder (OCD) is a chronic, disabling disorder. Psychosurgery may be indicated for a subset of patients for whom no conventional treatment is satisfactory. This manuscript focuses on the stereotactic subcaudate tractotomy (SST). Thus far, these procedures have been carried out using frame-based stereotactic techniques. However, modern–highly accurate–frameless stereotactic procedures have successfully been introduced in neurosurgical practice. We developed a novel frameless stereotactic subcaudate tractotomy procedure with promising initial results in two patients suffering from intractable OCD. This is the first report on frameless SST. Future studies should examine whether other ablative stereotactic psychosurgery procedures can be done using frameless stereotactic methods.

Intraoperative brain deformation is one of the most important causes affecting the overall accuracy of image-guided neurosurgical procedures. One option for correcting for this deformation is to acquire three-dimensional (3-D) ultrasound data during the operation and use this data to update the information provided by the preoperatively acquired MR data. For 12 patients 3-D ultrasound images have been reconstructed from freehand sweeps acquired during neurosurgical procedures. Ultrasound data acquired prior to and after opening the dura, but prior to surgery, have been quantitatively compared to the preoperatively acquired MR data to estimate the rigid component of brain shift at the first stages of surgery. Prior to opening the dura the average brain shift measured was 3.0 mm parallel to the direction of gravity, with a maximum of 7.5 mm, and 3.9 mm perpendicular to the direction of gravity, with a maximum of 8.2 mm. After opening the dura the shift increased on average 0.2 mm parallel to the direction of gravity and 1.4 mm perpendicular to the direction of gravity. Brain shift can be detected by acquiring 3-D ultrasound data during image-guided neurosurgery. Therefore, it can be used as a basis for correcting image data and preoperative planning for intraoperative deformations.

Object. We aimed to develop an auditory feedback system to be used in addition to regular neuronavigation, in an attempt to improve the usefulness of the information offered by neuronavigation systems.Instrumentation. Using a serial connection, instrument co-ordinates determined by a commercially available neuronavigation system were transferred to a laptop computer. Based on preoperative segmentation of the images, the software on the laptop computer produced an audible signal whenever the instrument moved into an area the surgeon wanted to avoid.Methods. To evaluate the impact of our setup on volumetric resections, phantom experiments were conducted. CT scans were acquired from eight blocks of floral foam. In each of these scans, a target-volume was segmented. This target-volume was subsequently resected using either regular neuronavigation or neuronavigation extended with auditory feedback. A 'postoperative' CT scan was used to compare the resection cavity to the preoperatively planned target-volume.Findings. The resemblance between the resection cavity and the target-volume was greater each time auditory feedback had been used. This corresponded with more complete removal of the target-volume. However, it also corresponded with the removal of more non-target 'tissue' in two out of four cases.Conclusions. The usefulness of auditory feedback was made plausible and the use of a new type of navigation phantom was illustrated. Based on these results, we recommend incorporation of auditory feedback, in commercially available neuronavigation systems, especially since this is relatively inexpensive.

Rationale and objective This article presents the evaluation of an interactive multiscale watershed segmentation algorithm for segmenting tumors in magnetic resonance brain images of patients scheduled for neuronavigational procedures. Materials and methods The watershed method is compared with manual delineation with respect to accuracy, repeatability, and efficiency. Results In the 20 patients included in this study, the measured volume of the tumors ranged from 2.7 to 81.9 cm 3 . A comparison of the tumor volumes measured with watershed segmentation to the volumes measured with manual delineation shows that the two methods are interchangeable according to the Bland and Altman criterion, and thus equally accurate. The repeatability of the watershed method and the manual method are compared by looking at the similarity of the segmented volumes. The similarity for intraobserver and interobserver variability for watershed segmentation is 96.4% and 95.3%, respectively, compared with 93.5% and 90.0% for manual outlining, from which it may be concluded that the watershed method is more repeatable. Moreover, the watershed algorithm is on average three times faster than manual outlining. Conclusion The watershed method has an accuracy comparable to that of manual delineation and outperforms manual outlining on the criteria of repeatability and efficiency.

¶Object. The aim of this study was to assess the clinical usefulness and accuracy of robot-assisted frameless stereotactic brain biopsies with a recently introduced MKM-mounted instrument holder. Methods. Twenty-three patients with intracranial lesions participated in this study. Depending on the size of the intracranial lesion, fiducials for image-to-patient co-ordinate transformation consisted either of bone screws or adhesive markers. Shortly after surgery, postoperative MRI-imaging was performed to demonstrate the location of the biopsy site. These images were compared with the preoperative images to assess the biopsy localisation error. Results. Postoperative biopsy sites could be demonstrated in six patients with bone screws and in 14 with adhesive markers. These two subgroups yielded average biopsy localisation errors of 3.3 mm (SD 1.7 mm) and 4.5 mm (SD 2.0 mm) respectively. This difference was not statistically significant. One biopsy was located in a liquefied haematoma. All others yielded pathological tissue. There were two postoperative haemorrhages, of which only one was temporarily symptomatic. There was no mortality in the first 30 days after surgery. Conclusions. Robot-assisted frameless point-stereotactic techniques represent an alternative to frame-based techniques for the performance of stereotactic biopsies.

In recent years, surgical navigation systems have become equipped to allow incorporation of data such as functional neuronavigation data. Functional magnetic resonance (fMR) imaging is a noninvasive modality that demonstrates various brain functions. Although still in an experimental stage, fMR imaging is a promising tool for mapping of motor and language functions. One advantage is that it can be implemented in presurgical imaging protocols and is therefore potentially widely available in general neurosurgical practice. In this paper the integration of fMR imaging and surgical navigation is described, and the potential advantages and pitfalls of its application in clinical practice are discussed.

To improve the usefulness of the information offered by neuronavigation systems, we developed an auditive feedback system which can be used in addition to regular neuronavigation. Using a serial connection, instrument coordinates determined by a commercially available neuronavigation system were transferred to a laptop computer. Based on preoperative segmentation of the images, the software on the laptop computer produced an audible signal whenever the instrument moved into an area the surgeon wanted to avoid. Phantom experiments were conducted to evaluate the impact of this setup on volumetric resections. These consisted of the ‘resection’ of a preoperatively defined target-volume from eight blocks of floral foam using CT-based navigation, four with and four without the auditive feedback extension. The resemblance between the resection cavity, as demonstrated by a postoperative CT scan, and the target-volume was greater each time auditive feedback had been used. This corresponded with more complete removal of the target-volume in all cases and the removal of more nontarget ‘tissue’ in two out of four cases. Our results make the usefulness of auditive feedback plausible and, consequently, we recommend the relatively inexpensive incorporation of auditive feedback in commercially available neuronavigation systems.

✓ To enable the use of the Mehrkoordinaten Manipulator (MKM) robotic navigation system for frameless point stereotactic procedures, a new instrument holder is presented. A phantom-based accuracy study was performed in which this new method was compared with frame-based procedures performed using the Brown-Roberts-Wells (BRW) stereotactic frame. The authors acquired computerized tomography scans of a test phantom, consisting of 19 acrylic plastic target rods on a circular base. These images were used in frame-based (BRW) and frameless (MKM) localization experiments. In both cases the authors calculated the distances between the actual target positions and the positions reached stereotactically. The mean application accuracy (target registration error) was 0.68 mm when the BRW frame was used and 0.96 mm when the MKM system was used after manual repositioning of the microscope (p < 0.001). Positioning accomplished using robotics only demonstrated a slightly larger inaccuracy: 1.47 mm (p < 0.005). Because the surgeon is concerned with the largest error in an individual case rather than the mean error in a large number of cases, the mean + three standard deviations was also compared. This value differed very little between the manually positioned MKM system and the BRW frame (2.04 mm and 1.84 mm, respectively). Although repeatability per target appeared to be slightly better when the BRW frame was used, accuracy was more homogeneous over the phantom volume when the MKM system was used (both differences were not significant). In conclusion, the accuracy of point stereotactic procedures performed using an instrument holder attached to the MKM system is comparable with the accuracy of procedures involving a stereotactic frame. Moreover, the frameless techniques and robotic features of the MKM enable a more surgeon- and patient-friendly stereotactic procedure.

In an experimental animal exercise model we tested whether daily administration of prednisone prevents the development of mechanically induced muscle fibre damage. Six-week-old rats were treated with different doses of prednisone ranging from 1 to 50 mg/kg body weight per day or with placebo, for 8 days. On day 6 of treatment the rats were forced to run for 2 h on a level treadmill. Two days after exercise morphological damage in the soleus muscles was quantified using light microscopy and a semi-automatic image analysis system. Creatine kinase (CK) activity was measured before exercise (day 5) and directly after exercise (day 6). The expression of dystrophin in a placebo group and in a group that received 5 mg prednisone/kg body weight per day with and without performing exercise was studied with Western blotting. The effect of prednisone on fibre type distribution was determined with an antibody against fast myosin and the effect of prednisone on the proliferative activity of muscle satellite cells was studied using bromodeoxyuridine (BrdU) immunohistochemistry. Exercise-induced muscle fibre damage varied in a dose-dependent way. In the placebo group the mean (SEM) damaged muscle fibre area was 4% (1%). The groups that received low doses of prednisone, 1 or 2.5 mg/kg per day, showed a similar level of muscle damage. However, with 5 mg prednisone/kg per day the amount of muscle fibre damage [mean (SEM)] was significantly reduced to 1.4% (0.5%) (Por= 0.05, Student's t-test). High doses of prednisone had no protective effect. Directly after exercise the CK activity was increased two-fold, except in the group that received 50 mg prednisone/kg body weight per day. No changes in the amount of dystrophin were found after densitometric analysis of the Western blots. Prednisone did not affect the fibre distribution or the labelling index of satellite cells. We conclude that prednisone, given in an appropriate dose, protects muscle fibres against the development of mechanically induced damage, possibly by stabilizing the muscle fibre membranes. This action may explain the beneficial effect of prednisone observed in Duchenne muscular dystrophy patients.

Time resolved whole brain CT angiography (4D-CTA) is a novel imaging technology providing information regarding blood flow. One of the factors that influence the diagnostic value of this examination is the temporal resolution, which is affected by the gantry rotation speed during acquisition and the reconstruction interval during post-processing. Post-processing determines the time spacing between two reconstructed volumes and, unlike rotation speed, does not affect radiation burden. The data sets of six patients who underwent a cranial 4D-CTA were used for this study. Raw data was acquired using a 320-slice scanner with a rotation speed of 2 Hz. The arterial to venous passage of an intravenous contrast bolus was captured during a 15 s continuous scan. The raw data was reconstructed using four different reconstruction-intervals: 0.2, 0.3, 0.5 and 1.0 s. The results were rated by two observers using a standardized score sheet. The appearance of each lesion was rated correctly in all readings. Scoring for quality of temporal resolution revealed a stepwise improvement from the 1.0 s interval to the 0.3 s interval, while no discernable improvement was noted between the 0.3 s and 0.2 s interval. An increase in temporal resolution may improve the diagnostic quality of cranial 4D-CTA. Using a rotation speed of 0.5 s, the optimal reconstruction interval appears to be 0.3 s, beyond which, changes can no longer be discerned.

BACKGROUND AND PURPOSE: The criterion standard to diagnose and classify cranial DAVFs is DSA. Since this is invasive, relatively expensive and time-consuming, a noninvasive alternative is of interest. We aimed to evaluate the capabilities and pitfalls of 4D-CTA in a consecutive series of patients who presented with a newly diagnosed cranial DAVF, as demonstrated by conventional DSA. MATERIALS AND METHODS: Eleven patients were included in this study after biplane DSA demonstrated a cranial DAVF. They subsequently underwent 4D-CTA imaging by using a 320-detector CT scanner. DSA and 4D-CTA studies were independently read by 2 blinded observers, by using a standardized scoring sheet. 4D-CTA results were analyzed with DSA as the criterion standard. RESULTS: In 10 cases, there was full agreement between DSA and 4D-CTA regarding the Borden classification. However, in the remaining patient, a slow-filling DAVF with a low shunt volume was missed by both readers on 4D-CTA. In all 10 detected cases, ≥1 of the major contributing arteries could be identified with 4D-CTA. Although, by using DSA, the 2 observers identified additional arterial feeders in 7 and 8 cases, respectively, these discrepancies did not influence clinical decision making. CONCLUSIONS: Although novel 4D-CTA imaging may not rule out a small slow-flow DAVF, it appears to be a valuable new adjunct in the noninvasive diagnostic work-up, treatment planning, and follow-up of patients with cranial DAVFs.

Current computed tomography angiography (CTA) postprocessing tools do not support quantitative assessment of intravascular physiology. Dynamic volumetric CT, acquired at a sufficiently high temporal resolution, is ideal for such analysis. Following preliminary experiments in flow phantoms, we examine the segmentation of blood vessels from 4D CT angiography by curve fit and encoding of functional blood flow information into the resulting functional intravascular maps.Flow phantoms were constructed consisting of a single pipe input and 4 simultaneous outputs of varying flow rates. Two outflow pipe diameters were tested. Bolus transit time (TT), time to peak (TTP), and time of arrival (TOA) were analyzed using contrast bolus profiles generated from 4D volumetric CT examinations on a 320 detector scanner in regions of interest placed 10 cm apart in all outflow pipes. Six subjects with various neurovascular lesions were next examined using a volumetric contrast-enhanced 4D CT angiography protocol. Segmentation was performed by quadratic curve fit after comparative analysis and optimization of the segmentation technique using quadratic curves, the gamma variate function, and a simplified formulation of the gamma variate function. After segmentation, quantitative analysis of spatially congruent intravascular voxels including TTP, rise, TT, and slope of the contrast upstroke was employed to encode physiologic information into the segmentations and produce intravascular functional maps. Comparison was made in each case to the patient's routine imaging.Increasing volumetric flow rates correspond to reduction of bolus TT in flow phantoms. TT elongation was observed as the contrast bolus moved distally in all pipes, with greater elongation seen at slower flow rates and larger pipe diameters. A greater difference was observed between TTP proximally and distally in pipes compared with TOA, an effect most prominent at slower flow rates and larger pipe lumens, and thus TTP was chosen for functional encoding into segmentations of the clinical series. In vivo, the quadratic function demonstrated the lowest coefficient of variation when fit to intravascular time density series and outperformed 2 formulations of the gamma variate function. After segmentation with quadratic curves, Gaussian distributions were chosen over gamma variate functions to characterize contrast bolus profiles while neglecting recirculation and to calculate functional parameters for spatial encoding. Intravascular functional maps free of bone artifacts were created in every case that demonstrated all appropriate vessels and showed agreement with conventional imaging modalities in terms of vessel delineation and the diagnosis of vascular pathology. The most useful and interesting functional maps are discussed in each case.The above approach to quantitative CT angiography provides a method of evaluating dynamic CTA data by means of intravascular functional maps. The techniques are broadly applicable in the clinical assessment of a variety of vascular diseases.

Novel 320-section CT scanning equipment enables dynamic noninvasive angiographic imaging of the entire cranial vasculature (4D-CTA). We describe this technique and demonstrate its potential in arteriovenous shunting lesions. 4D-CTA imaging resulted in a correct diagnosis, lesion classification, and treatment-strategy selection in 3 patients, compared with CA. We think that 4D-CTA can further reduce the need for CA, sparing the patient the discomfort and risk associated with an invasive procedure.

The aim of this study is to report the authors' initial clinical experience of a 320-detector row computed tomography (CT) scanner in cerebrovascular disorders. Volumetric CT using the full 160-mm width of the 320 detector rows enables full brain coverage in a single rotation that allows for combined time-resolved whole-brain perfusion and four-dimensional CT angiography (CTA). The protocol for the combined dynamic CTA and CT perfusion (CTP) is presented, and its potential applications in stroke, stenoocclusive disease, arteriovenous malformations and dural shunts are reviewed based on clinical examples. The combined CTA/CTP data can provide visualization of dynamic flow and perfusion as well as motion of an entire volume at very short time intervals which is of importance in a variety of pathologies with altered cerebral hemodynamics. The broad coverage enabled by 320 detector rows offers z-axis coverage allowing for whole-brain perfusion and subtracted dynamic angiography of the entire intracranial circulation.

In this study the authors measured the effect of auditory feedback during image-guided surgery (IGS) in a phantom model and in a clinical setting. In the phantom setup, advanced IGS with complementary auditory feedback was compared with results obtained with 2 routine forms of IGS, either with an on-screen image display or with image injection via a microscope. The effect was measured by means of volumetric resection assessments. The authors also present their first clinical data concerning the effects of complementary auditory feedback on instrument handling during image-guided neurosurgery. When using image-injection through the microscope for navigation, however, resection quality was significantly worse. In the clinical portion of the study, the authors performed resections of cerebral mass lesions in 6 patients with the aid of auditory feedback. Instrument tip speeds were slightly (although significantly) influenced by this feedback during resection. Overall, the participating neurosurgeons reported that the auditory feedback helped in decision-making during resection without negatively influencing instrument use. Postoperative volumetric imaging studies revealed resection rates ofor = 95% when IGS with auditory feedback was used. There was only a minor amount of brain shift, and postoperative resection volumes corresponded well with the preoperative intentions of the neurosurgeon. Although the results of phantom surgery with auditory feedback revealed no significant effect on resection quality or extent, auditory cues may help prevent damage to eloquent brain structures.

To improve the efficacy of tumor resection in image guided neurosurgery, two new types of feedback were investigated. Firstly, sound feedback to give the surgeons a warning signal when the instrument tip approaches normal/non-planned brain tissue. Secondly, workflow feedback by logging and tagging all instrument positions in image space. Results from laboratory and clinic suggest that sound feedback seems to be useful but needs more fine tuning before it will be practical for clinical use. Workflow feedback, on the other hand, appears to be a simple, cheap and efficient method to give the surgeon insight in the progress of resection, to log locations of interest, and to give insight in brain deformations occurring during surgery.

Background The purpose of this study was to define the technical requirements of future (tele)robotic neurosurgical systems. We aimed to analyse the movements of surgical instruments during neurosurgical procedures. Methods A commercially available neuronavigation system (StealthStation TREONplus, Medtronic, USA) was used to determine the position and orientation of the surgical instrument. A custom-made log-mode was implemented in the software to file instrument coordinates intraoperatively. Data was collected during the debulking of malignant primary brain tumours, temporal epilepsy surgery and skull base tumour surgery. Results Maximum tip displacement velocity varied, per procedure, in the range 6.6–12.7 cm/s and maximum rotational speed 21–40 /s. Maximum instrument orientation differences within the volume of movement varied. The largest differences were detected during temporal epilepsy surgery (73° and 52° in the coronal and axial planes, respectively), while the smallest differences were detected in the debulking of an intraventricular tumour. Conclusions In this study, we have demonstrated the feasibility of motion analysis in image-guided neurosurgery. To mimic ordinary open neurosurgery, future neurosurgical (tele)robotic systems should at least support translational speeds up to 12.7 cm/s, rotational speeds up to 40 /s and differences in instrument orientation of up to 73 . Copyright © 2006 John Wiley & Sons, Ltd.

✓Three-dimensional rotational angiography is capable of exquisite visualization of cerebral blood vessels and their pathophysiology. Unfortunately, images obtained using this modality typically show a small region of interest without exterior landmarks to allow patient-to-image registration, precluding their use for neuronavigation purposes. The aim of this study was to find an alternative technique to enable 3D rotational angiography–guided vascular neurosurgery. Three-dimensional rotational angiograms were obtained in an angiographic suite with direct navigation capabilities. After image acquisition, a navigated pointer was used to touch fiducial positions on the patient's head. These positions were located outside the image volume but could nevertheless be transformed into image coordinates and stored in the navigation system. Prior to surgery, the data set was transferred to the navigation system in the operating room, and the same fiducial positions were touched again to complete the patient-to-image registration. This technique was tested on a Perspex phantom representing the cerebral vascular tree and on two patients with an intracranial aneurysm. In both the phantom and patients, the neuronavigation system provided 3D images representing the vascular tree in its correct orientation, that is, the orientation seen by the neurosurgeon through the microscope. In one patient, tissue shift was clearly observed without significant changes in the orientation of the structures. Results in this study demonstrate the feasibility of using 3D rotational angiography data sets for neuronavigation purposes. Determining the benefit of this type of navigation should be the subject of future studies.

The aim of this report is to introduce a simple modification to the free-hand frameless stereotactic placement of ventriculoperitoneal shunts in undersized ventricles. In this technical note, we describe our experience with ventricular catheter placement in two children suffering from shunt dependent idiopathic intracranial hypertension using an image-guided instrument holder with a catheter guide. In both patients, the surgical procedure proved to be easy and accurate, with good initial clinical results. The use of an image-guided instrument holder is a modification to the free-hand frameless stereotactic placement of ventriculoperitoneal shunts in undersized ventricles.

Object The goal of this study was to assess the impact of neuronavigation on the cytoreductive treatment of solitary contrast-enhancing intracerebral tumors and outcomes of this treatment in cases in which neuronavigation was preoperatively judged to be redundant. Methods The authors conducted a prospective randomized study in which 45 patients, each harboring a solitary contrast-enhancing intracerebral tumor, were randomized for surgery with or without neuronavigation. Peri- and postoperative parameters under investigation included the following: duration of the procedure; surgeon’s estimate of the usefulness of neuronavigation; quantification of the extent of resection, determined using magnetic resonance imaging; and the postoperative course, as evaluated by neurological examinations, the patient’s quality-of-life self-assessment, application of the Barthel index and the Karnofsky Performance Scale score, and the patient’s time of death. The mean amount of residual tumor tissue was 28.9% for standard surgery (SS) and 13.8% for surgery involving neuronavigation (SN). The corresponding mean amounts of residual contrast-enhancing tumor tissue were 29.2 and 24.4%, respectively. These differences were not significant. Gross-total removal (GTR) was achieved in five patients who underwent SS and in three who underwent SN. Median survival was significantly shorter in the SN group (5.6 months compared with 9 months, unadjusted hazard ratio = 1.6); however, this difference may be attributable to the coincidental early death of three patients in the SN group. No discernible important effect on the patients’ 3-month postoperative course was identified. Conclusions There is no rationale for the routine use of neuronavigation to improve the extent of tumor resection and prognosis in patients harboring a solitary enhancing intracerebral lesion when neuronavigation is not already deemed advantageous because of the size or location of the lesion.

This article presents the evaluation of an interactive multiscale watershed segmentation algorithm for segmenting tumors in magnetic resonance brain images of patients scheduled for neuronavigational procedures.The watershed method is compared with manual delineation with respect to accuracy, repeatability, and efficiency.In the 20 patients included in this study, the measured volume of the tumors ranged from 2.7 to 81.9 cm(3). A comparison of the tumor volumes measured with watershed segmentation to the volumes measured with manual delineation shows that the two methods are interchangeable according to the Bland and Altman criterion, and thus equally accurate. The repeatability of the watershed method and the manual method are compared by looking at the similarity of the segmented volumes. The similarity for intraobserver and interobserver variability for watershed segmentation is 96.4% and 95.3%, respectively, compared with 93.5% and 90.0% for manual outlining, from which it may be concluded that the watershed method is more repeatable. Moreover, the watershed algorithm is on average three times faster than manual outlining.The watershed method has an accuracy comparable to that of manual delineation and outperforms manual outlining on the criteria of repeatability and efficiency.

Intraoperative brain deformation is one of the most contributing factors to the inaccuracy of image-guided neurosurgery systems. One option for correcting for this deformation is to acquire 3D ultrasound images during surgery and use these to update the information provided by the preoperatively acquired MR. To compare ultrasound volumes at different stages of surgery, non-rigid registration techniques are necessary. We present the results of applying a non-rigid registration algorithm, based on free-form deformations using B-splines and using normalized mutual information as a similarity measure, to 3D ultrasound volumes of two patients with brain tumours. For these two patients we registered an ultrasound volume acquired prior to opening the dura with an ultrasound volume acquired after opening the dura, but prior to surgery. When comparing the segmented tumours after affine registration plus free-form registration with a control point spacing of 4 mm to the segmented tumour volumes after registration with the image-guided surgery system, the volume overlap increased from approximately 76% to 96% for both patients.

Intraoperative brain deformation is the most important cause affecting the overall accuracy of image guided neurosurgical procedures. One option for correcting this deformation is to acquire 3D ultrasound images during the operation and use these to update the information provided by the preoperatively acquired MR data.

Typically, frameless stereotactic systems present a crosshair indicating the localisation of an instrument relative to preoperative images. We aim to develop a model that enables three-dimensional graphical presentation of confidence intervals at the instrument’s position, during a surgical procedure. This requires the prediction of frameless stereotactic accuracy confidence intervals at any position within the surgical volume.

The visualization of brain vessels on the cortex helps the neurosurgeon in two ways: To avoid blood vessels when specifying the trepanation entry, and to overcome errors in the surgical navigation system due to brain shift. We compared 3D T1 MR, 3D T1 MR with gadolinium contrast, MR venography and MR phase contrast angiography as scanning techniques, mutual information as registration technique, and thresholding and multi-vessel enhancement as image processing techniques. We evaluated the volume rendered results based on their quality and correspondence with photos took during surgery. It appears that with 3D T1 MR scans, gadolinium is required to show cortical veins. The visibility of small cortical veins is strongly enhanced by subtracting a 3D T1 MR baseline scan, which should be registered to the scan with gadolinium contrast, even when the scans are made during the same session. Multi-vessel enhancement helps to clarify the view on small vessels by reducing the noise level, but strikingly does not reveal more. MR venography does show intracerebral veins with high detail, but is, as is, unsuited to show cortical veins due to the low contrast with CSF. MR phase contrast angiography can perform equally well as the subtraction technique, but its quality seems to show more inter-patient variability.

A volume rendering library is presented to interactively analyze volume data from modalities like CT, MR, PET, SPECT< and fMRI for the planning of nuerosurgical procedures. Current applications are logging of Penfield procedures, fMRI visualization, blood vessel visualization and interactive localization of EEG electrodes implanted in the subdural space of a patient with epilepsy.© (2001) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

The application accuracy of frameless stereotaxy depends partly on the accuracy of the patient-to-image registration procedure. We compared the application accuracy of registration procedures based on anatomical landmarks, surface matching, and adhesive markers. After acquisition of a 3D-MRI volume, 30 patients were subjected to all three registration procedures. Frameless stereotaxy was performed with the STN system (Carl Zeiss, Germany). Following each registration procedure, the root-mean-squared-error (RMSE) and the target registration error (TRE) of an extra adhesive marker (target) were recorded. The first represents the goodness-of-fit of the registration procedure (not available in surface matching) while the second represents the application accuracy. The mean TRE+/- SD for each type of registration was 5.3+/- 2.1mm, 9.4+/- 6.6mm, and 3.6+/- 1.6mm (paired t-tests: p

The visualization of brain vessels on the cortex helps the neurosurgeon in two ways: to avoid blood vessels when specifying the trepanation entry, and to overcome errors in the surgical navigation system due to brain shift. We compared 3D T1, MR, 3D T1 MR with gadolinium contrast, MR venography as scanning techniques, mutual information as registration technique, and thresholding and multi-vessel enhancement as image processing techniques. We evaluated the volume rendered results based on their quality and correspondence with photos took during surgery. It appears that with 3D T1 MR scans, gadolinium is required to show cortical veins. The visibility of small cortical veins is strongly enhanced by subtracting a 3D T1 MR baseline scan, which should be registered to the scan with gadolinium contrast, even when the scans are made during the same session. Multi-vessel enhancement helps to clarify the view on small vessels by reducing noise level, but strikingly does not reveal more. MR venography does show intracerebral veins with high detail, but is, as is, unsuited to show cortical veins due to the low contrast with CSF.© (2000) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

A common abnormality in children seen by neurosurgeons is hydrocephalus. Normally, these patients are treated by placing an extracranial shunt to drain the abundant fluid from the ventricles of the brain. This shunting is subject to complications like infection and obstruction.

Introduction We aimed to evaluate the use of time-resolved whole-head CT angiography (4D-CTA) in patients with an untreated arteriovenous malformation of the brain (bAVM), as demonstrated by catheter angiography (DSA). Methods Seventeen patients with a DSA-proven bAVM were enrolled. These were subjected to 4D-CTA imaging using a 320 detector row CT scanner. Using a standardized scoring sheet, all studies were analyzed by a panel of three readers. This panel was blind to the DSA results at the time of reading the 4D-CTA. Results 4D-CTA detected all bAVMs. With regard to the Spetzler–Martin grade, 4D-CTA disagreed with DSA in only one case, where deep venous drainage was missed. Further discrepancies between 4D-CTA and DSA analyses included underestimation of the nidus size in small lesions (four cases), misinterpretation of a feeding vessel (one case), misinterpretation of indirect feeding through pial collaterals (three cases) and oversight of mild arterial enlargement (two cases). 4D-CTA correctly distinguished low-flow from high-flow lesions and detected dural/transosseous feeding (one case), venous narrowing (one case) and venous pouches (nine cases). Conclusion In this series, 4D-CTA was able to detect all bAVMs. Although some angioarchitectural details were missed or misinterpreted when compared to DSA, 4D-CTA evaluation was sufficiently accurate to diagnose the shunt and classify it. Moreover, 4D-CTA adds cross-sectional imaging and perfusion maps, helpful in treatment planning. 4D-CTA appears to be a valuable new adjunct in the non-invasive diagnostic work-up of bAVMs and their follow-up when managed conservatively.