Development of a CT-Compatible, Anthropomorphic Skull and Brain Phantom for Neurosurgical Planning, Training, and Simulation.

BACKGROUND: Neurosurgical procedures are complex and require years of training and experience. Traditional training on human cadavers is expensive, requires facilities and planning, and raises ethical concerns. Therefore, the use of anthropomorphic phantoms could be an excellent substitute. The aim of the study was to design and develop a patient-specific 3D-skull and brain model with realistic CT-attenuation suitable for conventional and augmented reality (AR)-navigated neurosurgical simulations. METHODS: The radiodensity of materials considered for the skull and brain phantoms were investigated using cone beam CT (CBCT) and compared to the radiodensities of the human skull and brain. The mechanical properties of the materials considered were tested in the laboratory and subsequently evaluated by clinically active neurosurgeons. Optimization of the phantom for the intended purposes was performed in a feedback cycle of tests and improvements. RESULTS: The skull, including a complete representation of the nasal cavity and skull base, was 3D printed using polylactic acid with calcium carbonate. The brain was cast using a mixture of water and coolant, with 4 wt% polyvinyl alcohol and 0.1 wt% barium sulfate, in a mold obtained from segmentation of CBCT and T1 weighted MR images from a cadaver. The experiments revealed that the radiodensities of the skull and brain phantoms were 547 and 38 Hounsfield units (HU), as compared to real skull bone and brain tissues with values of around 1300 and 30 HU, respectively. As for the mechanical properties testing, the brain phantom exhibited a similar elasticity to real brain tissue. The phantom was subsequently evaluated by neurosurgeons in simulations of endonasal skull-base surgery, brain biopsies, and external ventricular drain (EVD) placement and found to fulfill the requirements of a surgical phantom. CONCLUSIONS: A realistic and CT-compatible anthropomorphic head phantom was designed and successfully used for simulated augmented reality-led neurosurgical procedures. The anatomic details of the skull base and brain were realistically reproduced. This phantom can easily be manufactured and used for surgical training at a low cost.

Clot composition characterization using diffuse reflectance spectroscopy in acute ischemic stroke.

Acute ischemic stroke caused by large vessel occlusion is treated with endovascular thrombectomy, but treatment failure may occur when clot composition and thrombectomy technique mismatch. In this proof-of-concept study, diffuse reflectance spectroscopy (DRS) is evaluated for identification of clot composition ex vivo. DRS spectra and histology were acquired from 45 clot units retrieved from 29 stroke patients. DRS spectra correlated to clot RBC content, R= 81, p < .001, and could discriminate between RBC-rich and fibrin-rich clots, p < 0.001. Sensitivity and specificity for detection of RBC-rich clots were 0.722 and 0.846 respectively. Applied in an intravascular device, DRS could potentially provide intraprocedural information on clot composition that could increase endovascular thrombectomy efficiency.

Identifying clot composition using intravascular diffuse reflectance spectroscopy in a porcine model of endovascular thrombectomy.

BACKGROUND: Endovascular thrombectomy has revolutionized the management of acute ischemic stroke and proven superior to stand-alone intravenous thrombolysis for large vessel occlusions. However, failed or delayed revascularization may occur as a result of a mismatch between removal technique and clot composition. Determination of clot composition before thrombectomy provides the possibility to adapt the technique to improve clot removal efficacy. We evaluated the application of diffuse reflectance spectroscopy (DRS) for intravascular determination of clot composition in vivo. METHODS: Three clot types, enriched in red blood cells or fibrin or with a mixed content, were prepared from porcine blood and injected into the external carotids of a domestic pig. A guidewire-like DRS probe was used to investigate the optical spectra of clots, blood and vessel wall. Measurement positions were confirmed with angiography. Spectra were analyzed by fitting an optical model to derive physiological parameters. To evaluate the method's accuracy, photon scattering and blood and methemoglobin contents were included in a decision tree model and a random forest classification. RESULTS: DRS could differentiate between the three different clot types, blood and vessel wall in vivo (p<0.0001). The sensitivity and specificity for detection was 73.8% and 98.8% for red blood cell clots, 80.6% and 97.8% for fibrin clots, and 100% and 100% for mixed clots, respectively. CONCLUSION: Intravascular DRS applied via a custom guidewire can be used for reliable determination of clot composition in vivo. This novel approach has the potential to increase efficacy of thrombectomy procedures in ischemic stroke.

Diffuse reflectance spectroscopy sensor to differentiate between glial tumor and healthy brain tissue: a proof-of-concept study.

Glial tumors grow diffusely in the brain. Survival is correlated to the extent of tumor removal, but tumor borders are often invisible. Resection beyond the borders as defined by conventional methods may further improve prognosis. In this proof-of-concept study, we evaluate diffuse reflectance spectroscopy (DRS) for discrimination between glial tumors and normal brain ex vivo. DRS spectra and histology were acquired from 22 tumor samples and nine brain tissue samples retrieved from 30 patients. The content of biological chromophores and scattering features were estimated by fitting a model derived from diffusion theory to the DRS spectra. DRS parameters differed significantly between tumor and normal brain tissue. Classification using random forest yielded a sensitivity and specificity for the detection of low-grade gliomas of 82.0% and 82.7%, respectively, and the area under curve (AUC) was 0.91. Applied in a hand-held probe or biopsy needle, DRS has the potential to provide intra-operative tissue analysis.

Augmented reality navigation for cranial biopsy and external ventricular drain insertion.

OBJECTIVE: The aim of this study was to evaluate the accuracy (deviation from the target or intended path) and efficacy (insertion time) of an augmented reality surgical navigation (ARSN) system for insertion of biopsy needles and external ventricular drains (EVDs), two common neurosurgical procedures that require high precision. METHODS: The hybrid operating room-based ARSN system, comprising a robotic C-arm with intraoperative cone-beam CT (CBCT) and integrated video tracking of the patient and instruments using nonobtrusive adhesive optical markers, was used. A 3D-printed skull phantom with a realistic gelatinous brain model containing air-filled ventricles and 2-mm spherical biopsy targets was obtained. After initial CBCT acquisition for target registration and planning, ARSN was used for 30 cranial biopsies and 10 EVD insertions. Needle positions were verified by CBCT. RESULTS: The mean accuracy of the biopsy needle insertions (n = 30) was 0.8 mm ± 0.43 mm. The median path length was 39 mm (range 16-104 mm) and did not correlate to accuracy (p = 0.15). The median device insertion time was 149 seconds (range 87-233 seconds). The mean accuracy for the EVD insertions (n = 10) was 2.9 mm ± 0.8 mm at the tip with a 0.7° ± 0.5° angular deviation compared with the planned path, and the median insertion time was 188 seconds (range 135-400 seconds). CONCLUSIONS: This study demonstrated that ARSN can be used for navigation of percutaneous cranial biopsies and EVDs with high accuracy and efficacy.

The Ki-67 Proliferation Index as a Marker of Time to Recurrence in Intracranial Meningioma.

BACKGROUND: There are examples of incongruence between the WHO grade and clinical course in meningioma patients. This incongruence between WHO grade and recurrence has led to search for other prognostic histological markers. OBJECTIVE: To study the correlation between the Ki-67 proliferative index (PI), risk of recurrence, and recurrence rates in meningioma patients. METHODS: We prospectively collected pathological diagnosis of de novo consecutive meningiomas. In total, we followed 159 patients with clinical controls until recurrence, death, or emigration. We estimated the correlation between risk of recurrence and Ki-67 PI when adjusted for age at diagnosis, sex, WHO grade, extent of surgical resection, and tumor location. We estimated the cumulative incidence of recurrence when considering death without recurrence a competing risk. We report recurrence rates per 100 person-years. RESULTS: A 1%-point increase of Ki-67 PI yielded a hazard ratio of 1.12 (95% CI: 1.01-1.24) in a multivariate analysis. The cumulative incidence of recurrence was 3% for Ki-67 0% to 4% vs 19% for Ki-67 > 4% meningiomas after 1 yr, but 24% vs 35%, respectively, after 10 yr. There was no significant difference in mean Ki-67 PI between nonrecurrent and recurrent meningioma in a 2-sample t-test (P = .08). The strongest relationship was detected between Ki-67 PI and time to recurrence: Ki-67 < 4% meningiomas recurred after median 4.8 yr, compared to 0.60 to 0.75 yr for patients with higher Ki-67 PI. CONCLUSION: Ki-67 PI was a marker for time to recurrence rather than a predictor of recurrence. Ki-67 PI may be utilized for patient tailored follow-up.

Preoperative antibiotic prophylaxis regimen in brain tumour surgery in Sweden: a quasi-experimental study.

BACKGROUND: There has been varied clinical practice concerning antibiotic prophylaxis in patients undergoing craniotomy. In Sweden, both Cloxacillin and Cefuroxime have frequently been used. We aimed to study the clinical effectiveness of these two regimens. METHODS: A quasi-experimental design was used. The sample consisted of 580 adult (> 18 years) patients operated 2012-2015, of which 375 received Cloxacillin (pre-intervention group) and 205 received Cefuroxime (intervention group). Primary endpoint was the incidence of surgical site infection (SSI) 12 months after surgery, while secondary endpoints were the need for reoperation due to SSI, the amount antibiotics used and the number of visits in the outpatient clinic related to SSI. A control group from another institution was reviewed to rule out clinical trial effects. RESULTS: When analysed by intention to treat, the pre-intervention group had a significant higher incidence of SSI, 13.3% (50/375) vs 5.4% (11/205) in the intervention group (p < 0.01). A treatment per protocol analysis confirmed the result. The number of reoperations due to SSI were significantly reduced in the intervention group, 3.4% (7/205) vs 8.3% (31/375) (p = 0.02), as was the total antibiotic use (p = 0.03) and the number of visits in the outpatient clinic (p < 0.01). In the control group, the reoperation rate as result of SSI was lower (p = 0.02) prior to the opposite change from Cefuroxime to Cloxacillin, 1.8% (27/1529) vs 3.1% (43/1378). CONCLUSION: In Sweden, Cefuroxime as prophylaxis in brain tumour surgery by craniotomy seems to be superior to Cloxacillin.

Correction: Fusion of augmented reality imaging with the endoscopic view for endonasal skull base surgery; a novel application for surgical navigation based on intraoperative cone beam computed tomography and optical tracking.

[This corrects the article DOI: 10.1371/journal.pone.0227312.].

Fusion of augmented reality imaging with the endoscopic view for endonasal skull base surgery; a novel application for surgical navigation based on intraoperative cone beam computed tomography and optical tracking.

OBJECTIVE: Surgical navigation is a well-established tool in endoscopic skull base surgery. However, navigational and endoscopic views are usually displayed on separate monitors, forcing the surgeon to focus on one or the other. Aiming to provide real-time integration of endoscopic and diagnostic imaging information, we present a new navigation technique based on augmented reality with fusion of intraoperative cone beam computed tomography (CBCT) on the endoscopic view. The aim of this study was to evaluate the accuracy of the method. MATERIAL AND METHODS: An augmented reality surgical navigation system (ARSN) with 3D CBCT capability was used. The navigation system incorporates an optical tracking system (OTS) with four video cameras embedded in the flat detector of the motorized C-arm. Intra-operative CBCT images were fused with the view of the surgical field obtained by the endoscope's camera. Accuracy of CBCT image co-registration was tested using a custom-made grid with incorporated 3D spheres. RESULTS: Co-registration of the CBCT image on the endoscopic view was performed. Accuracy of the overlay, measured as mean target registration error (TRE), was 0.55 mm with a standard deviation of 0.24 mm and with a median value of 0.51mm and interquartile range of 0.39--0.68 mm. CONCLUSION: We present a novel augmented reality surgical navigation system, with fusion of intraoperative CBCT on the endoscopic view. The system shows sub-millimeter accuracy.

Hyperbaric Oxygen Therapy as Adjuvant Treatment for Hardware-Related Infections in Neuromodulation.

BACKGROUND: In neuromodulation therapies, hardware-related infections are a major challenge often leading to hardware removal. OBJECTIVE: To investigate the role of adjuvant hyperbaric oxygen therapy (HBOT) in hardware-related infections. METHODS: Fourteen hardware-related infection events in 12 consecutive patients between 2002 and 2015 were treated with antibiotics and adjuvant HBOT at the Karolinska University Hospital (Stockholm, Sweden). Two time-independent infection events related to hardware replacements occurred in 2 patients. Infection resolution and the need for hardware removal were assessed. RESULTS: Twelve out of 14 events of hardware-related infection were successfully treated without hardware removal (86%). The 2 patients treated twice with HBOT on 2 time-independent occasions could retain their hardware in both cases. Hardware was removed following HBOT failure in 2 infection events, with long-term infection control achieved in all patients. Further, an intrathecal pump malfunction caused by HBOT at 2.8 bars was observed, leading to a change in the manufacturer's guidelines. CONCLUSIONS: This study indicates a potential benefit of adjuvant HBOT in the treatment of hardware-related infections in neuromodulation, diminishing the need for hardware removal and treatment interruption. Prospective studies are warranted to establish the role of adjuvant HBOT in the treatment of hardware-related infections in neuromodulation.

Long-term control and predictors of seizures in intracranial meningioma surgery: a population-based study.

BACKGROUND: The aim of this retrospective study was to investigate the long-term seizure control and antiepileptic drug (AED) prescriptions, as well as identifying predictors of seizure(s) before and after surgery in a population-based cohort of operated intracranial meningioma patients. METHODS: A total of 113 consecutive adult (> 18 years old) patients with newly diagnosed meningioma operated at the Karolinska University Hospital between 2006 and 2008 were included and followed up until the end of 2015. Data on seizure activity and AED prescriptions were obtained through chart review and telephone interview. Logistic regression and survival analysis were applied to identify risk factors for pre- and postoperative seizures. RESULTS: A total of 21/113 (18.6%) patients experienced seizures before surgery of which 8/21 (38.1%) went on to become seizure-free after surgery. Thirteen (14%) patients experienced new-onset seizures after surgery. The regression analysis revealed tumor diameter ≥ 3.5 cm as a risk factor for preoperative seizures (OR 3.83, 95% CI 1.14-12.87). Presence of headache (OR 0.19, 95% CI 0.05-0.76) and skull base tumor location (OR 0.14, 95% CI 0.04-0.44) decreased the risk of preoperative seizures. Postoperative seizures were associated with tumor diameter ≥ 3.5 cm (OR 2.65, 95% CI 1.06-6.62) and history of preoperative seizures (OR 3.50, 95% CI 1.55-7.90). CONCLUSION: Seizures are common before and after intracranial meningioma surgery. Approximately one third of patients with preoperative seizures become seizure-free on long-term follow-up after surgery, while 14% experienced new-onset seizures after surgery. Larger tumor size, absence of headache, and non-skull base location were associated with preoperative seizures, while tumor size and preoperative seizures were associated with postoperative seizures.

Surgical Replacement of Implantable Pulse Generators in Deep Brain Stimulation: Adverse Events and Risk Factors in a Multicenter Cohort.

BACKGROUND: Deep brain stimulation (DBS) is a growing treatment modality, and most DBS systems require replacement of the implantable pulse generator (IPG) every few years. The literature regarding the potential impact of adverse events of IPG replacement on the longevity of DBS treatments is rather scarce. OBJECTIVE: To investigate the incidence of adverse events, including postoperative infections, associated with IPG replacements in a multicenter cohort. METHODS: The medical records of 808 patients from one Australian and five Swedish DBS centers with a total of 1,293 IPG replacements were audited. A logistic regression model was used to ascertain the influence of possible predictors on the incidence of adverse events. RESULTS: The overall incidence of major infections was 2.3% per procedure, 3.7% per patient and 1.7% per replaced IPG. For 28 of 30 patients this resulted in partial or complete DBS system removal. There was an increased risk of infection for males (OR 3.6, p = 0.026), and the risk of infection increased with the number of prior IPG replacements (OR 1.6, p < 0.005). CONCLUSIONS: The risk of postoperative infection with DBS IPG replacement increases with the number of previous procedures. There is a need to reduce the frequency of IPG replacements.

Hyperbaric oxygen therapy in spontaneous brain abscess patients: a population-based comparative cohort study.

BACKGROUND: There is a need to improve outcome in patients with brain abscesses and hyperbaric oxygen therapy (HBOT) is a promising treatment modality. The objective of this study was to evaluate HBOT in the treatment of intracranial abscesses. METHOD: This population-based, comparative cohort study included 40 consecutive adult patients with spontaneous brain abscess treated surgically between January 2003 and May 2014 at our institution. Twenty patients received standard therapy with surgery and antibiotics (non-HBOT group), while the remaining 20 patients also received adjuvant HBOT (HBOT group). RESULTS: Resolution of brain abscesses and infection was seen in all patients. Two patients had reoperations after HBOT initiation (10 %), while nine patients (45 %) in the non-HBOT group underwent reoperations (p = 0.03). Of the 26 patients who did not receive HBOT after the first surgery, 15 (58 %) had one or several recurrences that lead to a new treatment: surgery (n = 11), surgery + HBO (n = 5) or just HBO (n = 1). In contrast, recurrences occurred in only 2 of 14 (14 %) who did receive HBOT after the first surgery (p < 0.01). A good outcome (Glasgow Outcome Score [GOS] of 5) was achieved in 16 patients (80 %) in the HBOT cohort versus 9 patients (45 %) in the non-HBOT group (p = 0.04). CONCLUSIONS: HBOT was associated with less treatment failures and need for reoperation and seemingly with improved long-term outcome. Further, HBOT was well tolerated and safe. Prospective studies are warranted to establish the role of HBOT in the treatment of brain abscesses.

Idiopathic intracranial hypertension and transverse sinus stenoses.

An 18-year-old woman was diagnosed with idiopathic intracranial hypertension (IIH) and bilateral transverse sinus stenoses (TSS), after presenting with papilledema and decreased visual acuity. Lumbar puncture revealed an opening pressure of >60 cm H2O. MRI showed bilateral TSS believed to be associated with the IIH. Initial treatment consisted of symptom relief by a temporary lumbar drain for cerebrospinal fluid (CSF) diversion, while the pros and cons of a more permanent solution by insertion of a ventriculoperitoneal shunt (VPS) or bilateral transverse sinus stent was discussed. A VPS was inserted since the patient had improved with CSF diversion. MRI verified reopening of the venous sinuses after shunt placement, and the patient remains asymptomatic with no signs of relapse after 3 years of follow-up.