Brain Shift during Staged Deep Brain Stimulation for Movement Disorders.

INTRODUCTION: Deep brain stimulation (DBS) is a routine neurosurgical procedure utilized to treat various movement disorders including Parkinson's disease (PD), essential tremor (ET), and dystonia. Treatment efficacy is dependent on stereotactic accuracy of lead placement into the deep brain target of interest. However, brain shift attributed to pneumocephalus can introduce unpredictable inaccuracies during DBS lead placement. This study aimed to determine whether intracranial air is associated with brain shift in patients undergoing staged DBS surgery. METHODS: We retrospectively evaluated 46 patients who underwent staged DBS surgery for PD, ET, and dystonia. Due to the staged nature of DBS surgery at our institution, the first electrode placement is used as a concrete fiducial marker for movement in the target location. Postoperative computed tomography (CT) images after the first electrode implantation, as well as preoperative, and postoperative CT images after the second electrode implantation were collected. Images were analyzed in stereotactic targeting software (BrainLab); intracranial air was manually segmented, and electrode shift was measured in the x, y, and z plane, as well as a Euclidian distance on each set of merged CT scans. A Pearson correlation analysis was used to determine the relationship between intracranial air and brain shift, and student's t test was used to compare means between patients with and without radiographic evidence of intracranial air. RESULTS: Thirty-six patients had pneumocephalus after the first electrode implantation, while 35 had pneumocephalus after the second electrode implantation. Accumulation of intracranial air following the first electrode implantation (4.49 ± 6.05 cm3) was significantly correlated with brain shift along the y axis (0.04 ± 0.35 mm; r (34) = 0.36; p = 0.03), as well as the Euclidean distance of deviation (0.57 ± 0.33 mm; r (34) = 0.33; p = 0.05) indicating statistically significant shift on the ipsilateral side. However, there was no significant correlation between intracranial air and brain shift following the second electrode implantation, suggesting contralateral shift is minimal. Furthermore, there was no significant difference in brain shift between patients with and without radiographic evidence of intracranial air following both electrode implantation surgeries. CONCLUSION: Despite observing volumes as high as 22.0 cm3 in patients with radiographic evidence of pneumocephalus, there was no significant difference in brain shift when compared to patients without pneumocephalus. Furthermore, the mean magnitude of brain shift was <1.0 mm regardless of whether pneumocephalus was presenting, suggesting that intracranial air accumulation may not produce clinical significant brain shift in our patients.

Quantitative Validation of the Correlation Between Optimized Pyramidal Tract Delineation After Brain Shift Compensation and Direct Electrical Subcortical Stimulation During Brain Tumor Surgery.

It remains unclear whether tractography of pyramidal tracts is correlated with the intraoperative direct electrical subcortical stimulation (DESS), and brain shift further complicates the issue. The objective of this research is to quantitatively verify the correlation between optimized tractography (OT) of pyramidal tracts after brain shift compensation and DESS during brain tumor surgery. OT was performed for 20 patients with lesions in proximity to the pyramidal tracts based on preoperative diffusion-weighted magnetic resonance imaging. During surgery, tumor resection was guided by DESS. A total of 168 positive stimulation points and their corresponding stimulation intensity thresholds were recorded. Using the brain shift compensation algorithm based on hierarchical B-spline grids combined with a Gaussian resolution pyramid, we warped the preoperative pyramidal tract models and used receiver operating characteristic (ROC) curves to investigate the reliability of our brain shift compensation method based on anatomic landmarks. Additionally, the minimum distance between the DESS points and warped OT (wOT) model was measured and correlated with DESS intensity threshold. Brain shift compensation was achieved in all cases, and the area under the ROC curve was 0.96 in the registration accuracy analysis. The minimum distance between the DESS points and the wOT model was found to have a significantly high correlation with the DESS stimulation intensity threshold (r = 0.87, P < 0.001), with a linear regression coefficient of 0.96. Our OT method can provide comprehensive and accurate visualization of the pyramidal tracts for neurosurgical navigation and was quantitatively verified by intraoperative DESS after brain shift compensation.

Photoacoustic-MR Image Registration Based on a Co-Sparse Analysis Model to Compensate for Brain Shift.

Brain shift is an important obstacle to the application of image guidance during neurosurgical interventions. There has been a growing interest in intra-operative imaging to update the image-guided surgery systems. However, due to the innate limitations of the current imaging modalities, accurate brain shift compensation continues to be a challenging task. In this study, the application of intra-operative photoacoustic imaging and registration of the intra-operative photoacoustic with pre-operative MR images are proposed to compensate for brain deformation. Finding a satisfactory registration method is challenging due to the unpredictable nature of brain deformation. In this study, the co-sparse analysis model is proposed for photoacoustic-MR image registration, which can capture the interdependency of the two modalities. The proposed algorithm works based on the minimization of mapping transform via a pair of analysis operators that are learned by the alternating direction method of multipliers. The method was evaluated using an experimental phantom and ex vivo data obtained from a mouse brain. The results of the phantom data show about 63% improvement in target registration error in comparison with the commonly used normalized mutual information method. The results proved that intra-operative photoacoustic images could become a promising tool when the brain shift invalidates pre-operative MRI.

Augmented Reality to Compensate for Navigation Inaccuracies.

This study aims to report on the capability of microscope-based augmented reality (AR) to evaluate registration and navigation accuracy with extracranial and intracranial landmarks and to elaborate on its opportunities and obstacles in compensation for navigation inaccuracies. In a consecutive single surgeon series of 293 patients, automatic intraoperative computed tomography-based registration was performed delivering a high initial registration accuracy with a mean target registration error of 0.84 ± 0.36 mm. Navigation accuracy is evaluated by overlaying a maximum intensity projection or pre-segmented object outlines within the recent focal plane onto the in situ patient anatomy and compensated for by translational and/or rotational in-plane transformations. Using bony landmarks (85 cases), there was two cases where a mismatch was seen. Cortical vascular structures (242 cases) showed a mismatch in 43 cases and cortex representations (40 cases) revealed two inaccurate cases. In all cases, with detected misalignment, a successful spatial compensation was performed (mean correction: bone (6.27 ± 7.31 mm), vascular (3.00 ± 1.93 mm, 0.38° ± 1.06°), and cortex (5.31 ± 1.57 mm, 1.75° ± 2.47°)) increasing navigation accuracy. AR support allows for intermediate and straightforward monitoring of accuracy, enables compensation of spatial misalignments, and thereby provides additional safety by increasing overall accuracy.

[Intraoperative brain shift in neuronavigation. Causes, clinical significance and solution of the problem]. / Intraoperatsionnoe smeshchenie mozga pri primenenii neironavigatsii. Prichiny, klinicheskaya znachimost' i puti resheniya problemy.

Intraoperative brain shift is the main cause of inaccurate navigation. This limits the use of both conventional and functional neuronavigation. Causes of brain shift are divided into surgical, pathophysiological and metabolic ones. Brain shift is usually unidirectional and directed towards gravitation. Brain dislocation depends on lesion size and its location. Shift is minimal in patients with tumors <20 ml and skull base neoplasms. Small craniotomy, retractor-free surgery and no ventriculostomy are valuable to reduce brain shift. Brain dislocation increases during surgery that's why marking of eloquent lesions at the beginning of surgery and primary resection near subcortical tracts minimize the risk of damage to conduction pathways. Augmented reality and manual shift of marked objects are the cornerstones of linear correction of brain shift in modern navigation systems. In case of nonlinear brain shift, sonography and intraoperative magnetic resonance imaging can clarify location of surgical target and cerebral structures.

Pneumocephalus in subthalamic deep brain stimulation for Parkinson's disease: a comparison of two different surgical techniques considering factors conditioning brain shift and target precision.

BACKGROUND: Precise placement of electrodes in deep brain stimulation (DBS) may be influenced by brain shift caused by cerebrospinal fluid leaking or air inflow. We compared accuracy and treatment outcomes between a standard technique and one aiming at reducing brain shift. METHODS: We retrospectively reviewed 46 patients (92 targets) treated with bilateral subthalamic-DBS for Parkinson's disease. The patients were divided into two groups: group A surgery was performed in supine position with standard burr hole, dural opening, fibrin glue and gelfoam plugging. Group B patients were operated in a semi-sitting position with direct dural puncture to reduce CSF loss. We analysed target deviation on head CT performed immediately after surgery and at 1 month merged with preoperative MRI planning. We recorded pneumocephalus volume, brain atrophy and target correction by intraoperative neurophysiology (ION). RESULTS: In group A, the mean pneumocephalus volume was 10.55 cm3, mean brain volume 1116 cm3, mean target deviation 1.09 mm and ION corrected 70% of targets. In group B, mean pneumocephalus was 7.60 cm3 (p = 0.3048), mean brain volume 1132 cm3 (p = 0.6526), mean target deviation 0.64 mm (p = 0.0074) and ION corrected 50% of targets (p = 0.4886). Most leads' deviations realigned to the planned target after pneumocephalus reabsorbtion suggesting a deviation caused by displacement of anatomical structures due to brain shift. Definitive lead position was always decided with ION. CONCLUSIONS: The modified DBS technique significantly reduced errors of electrode placement, though such difference was clinically irrelevant. ION corrected a high amount of trajectories in both groups (70% vs 50%). The choice of either strategy is acceptable.

How to avoid pneumocephalus in deep brain stimulation surgery? Analysis of potential risk factors in a series of 100 consecutive patients.

BACKGROUND: Accuracy of lead placement is the key to success in deep brain stimulation (DBS). Precise anatomic stereotactic planning usually is based on stable perioperative anatomy. Pneumocephalus due to intraoperative CSF loss is a common procedure-related phenomenon which could lead to brain shift and targeting inaccuracy. The aim of this study was to evaluate potential risk factors of pneumocephalus in DBS surgery. METHODS: We performed a retrospective single-center analysis in patients undergoing bilateral DBS. We quantified the amount of pneumocephalus by postoperative CT scans and corrected the data for accompanying brain atrophy by an MRI-based score. Automated computerized segmentation algorithms from a dedicated software were used. As potential risk factors, we evaluated the impact of trephination size, the number of electrode tracks, length of surgery, intraoperative blood pressure, and brain atrophy. RESULTS: We included 100 consecutive patients that underwent awake DBS with intraoperative neurophysiological testing. Systolic and mean arterial blood pressure showed a substantial impact with an inverse correlation, indicating that lower blood pressure is associated with higher volume of pneumocephalus. Furthermore, the length of surgery was clearly correlated to pneumocephalus. CONCLUSION: Our analysis identifies intraoperative systolic and mean arterial blood pressure as important risk factors for pneumocephalus in awake stereotactic surgery.

Placement accuracy of the second electrode in bilateral deep brain stimulation surgery.

PURPOSE: Due to brain shift during bilateral deep brain stimulation (DBS) surgery, placement of the second electrode may be subjected to more error than that of the first electrode. The authors aimed to investigate the accuracy of second electrode placement in this setting. MATERIALS AND METHODS: Fifty-five patients with Parkinson's disease who underwent bilateral DBS surgery (110 electrodes) were retrospectively evaluated. The targets were subthalamic nucleus (STN) and globus pallidus interna (GPi) in 40 and 15 cases, respectively. Preoperative planning and postoperative electrode images were co-registered to compare the error margin between the two sides. RESULTS: There is a statistically significant difference in the directional axis error along the y axis only when comparing each laterality (posterior 0.04 ± 1.21 mm vs anterior 0.41 ± 1.07 mm, p = 0.006). There is no significant difference of other error parameters, final track location, and number of microelectrode recording passes between the two sides. In a subgroup analysis, there is a significant difference in directional axis error along the y axis only in the STN subgroup (posterior 0.40 ± 1.05 mm vs anterior 0.18 ± 1.04 mm, p = 0.003). CONCLUSION: Although a statistically significant difference in directional axis error along the y axis was found between first and second electrode placements in the STN group but not in the GPi group, its magnitude is well below the clinically significant threshold.

Symptomatic Pneumocephalus after Deep Brain Stimulation Surgery: Report of 2 Cases.

BACKGROUND: Symptomatic pneumocephalus is an uncommon complication of cranial surgery. Reports of symptomatic pneumocephalus in deep brain stimulation (DBS) surgery are lacking, due to the rarity of this condition. The -authors describe 2 patients who experienced clinically significant intraparenchymal pneumocephalus as a consequence of DBS surgery and report their clinical presentations, treatments, and outcomes. Cases Descriptions: The first patient was a 69-year-old woman with Parkinson disease and the second was a 73-year-old woman with medically refractory essential tremor. Both patients underwent DBS implantation and developed focal neurological deficits in the days after surgery. In each case, immediate postoperative head computed tomography scans showed extra-axial pneumocephalus which redistributed on subsequent imaging along the dorsal length of the lead. For each patient, a second surgery was carried out to evacuate the pneumocephalus without lead removal. Clinical symptoms and radiological signs of intracranial air were resolved on the last follow-up. CONCLUSION: Symptomatic intraparenchymal pneumocephalus is a rare complication of DBS surgery which can be treated with surgical evacuation.

Factors Influencing Electrode Position and Bending of the Proximal Lead in Deep Brain Stimulation for Movement Disorders.

BACKGROUND: The introduction of intracranial air (ICA) during deep brain stimulation (DBS) surgery is thought to have a negative influence on targeting and clinical outcomes. OBJECTIVE: To investigate ICA volumes following surgery and other patient-specific factors as potential variables influencing translocation of the DBS electrode and proximal lead bowing. METHODS: High-resolution postoperative computed tomography scans (≤1.0 mm resolution in all directions) within 24 h following DBS surgery and 4-6 weeks of follow-up were acquired. A total of 50 DBS leads in 33 patients were available for analysis. DBS leads included Abbott/St. Jude Medical InfinityTM, Boston Scientific VerciseTM, and Medtronic 3389TM. RESULTS: Both ICA volume and anatomical target were significantly associated with measures of DBS electrode translocation. ICA volume and DBS lead model were found to be significant predictors of proximal lead bowing. Measures of proximal lead bowing and translocation along the electrode trajectory for the Medtronic 3389TM DBS lead were significantly larger than measures for the Abbott/St. Jude Medical InfinityTM and Boston Scientific VerciseTM DBS leads. CONCLUSION: The association between ICA volume and translocation of the DBS electrode is small in magnitude and not clinically relevant for DBS cases within a normal range of postoperative subdural air volumes. Differences in proximal lead bowing observed between DBS leads may reflect hardware engineering subtleties in the construction of DBS lead models.

Techniques for pneumocephalus and brain shift reduction in DBS surgery: a review of the literature.

Deep brain stimulation has become an established therapeutic choice to manage the symptoms of medically refractory Parkinson's disease. Its efficacy is highly dependent on the accuracy of electrodes' positioning in the correct anatomical target. During DBS procedure, the opening of the dura mater induces the displacement of neural structures. This effect mainly depends on the loss of the physiological negative intracranial pressure, air inflow, and loss of cerebrospinal fluid. Several studies concentrated on correcting surgical techniques for DBS electrodes' positioning in order to reduce pneumocephalus which may result in therapeutic failure. The authors focused in particular on reducing the brain air window and maintaining the pressure gradient between intra- and extracranial compartments. A significant reduction of pneumocephalus and brain shift was obtained by excluding the opening of the subarachnoid space, by covering the dura mater opening with tissue sealant and by reducing the intracranial pressure in general anesthesia. Smaller burr hole diameters were not statistically relevant for reducing air inflow and displacement of anatomical targets. The review of the literature showed that conserving a physiological intra-extracranial pressure gradient plays a fundamental role in avoiding pneumocephalus and consequent displacement of brain structures, which improves surgical accuracy and DBS long-term results.

Deformable MRI-Ultrasound registration using correlation-based attribute matching for brain shift correction: Accuracy and generality in multi-site data.

Intraoperative tissue deformation, known as brain shift, decreases the benefit of using preoperative images to guide neurosurgery. Non-rigid registration of preoperative magnetic resonance (MR) to intraoperative ultrasound (iUS) has been proposed as a means to compensate for brain shift. We focus on the initial registration from MR to predurotomy iUS. We present a method that builds on previous work to address the need for accuracy and generality of MR-iUS registration algorithms in multi-site clinical data. High-dimensional texture attributes were used instead of image intensities for image registration and the standard difference-based attribute matching was replaced with correlation-based attribute matching. A strategy that deals explicitly with the large field-of-view mismatch between MR and iUS images was proposed. Key parameters were optimized across independent MR-iUS brain tumor datasets acquired at 3 institutions, with a total of 43 tumor patients and 758 reference landmarks for evaluating the accuracy of the proposed algorithm. Despite differences in imaging protocols, patient demographics and landmark distributions, the algorithm is able to reduce landmark errors prior to registration in three data sets (5.37±4.27, 4.18±1.97 and 6.18±3.38 mm, respectively) to a consistently low level (2.28±0.71, 2.08±0.37 and 2.24±0.78 mm, respectively). This algorithm was tested against 15 other algorithms and it is competitive with the state-of-the-art on multiple datasets. We show that the algorithm has one of the lowest errors in all datasets (accuracy), and this is achieved while sticking to a fixed set of parameters for multi-site data (generality). In contrast, other algorithms/tools of similar performance need per-dataset parameter tuning (high accuracy but lower generality), and those that stick to fixed parameters have larger errors or inconsistent performance (generality but not the top accuracy). Landmark errors were further characterized according to brain regions and tumor types, a topic so far missing in the literature.

Asleep Deep Brain Stimulation Reduces Incidence of Intracranial Air during Electrode Implantation.

BACKGROUND: Asleep deep brain stimulation (aDBS) implantation replaces microelectrode recording for image-guided implantation, shortening the operative time and reducing cerebrospinal fluid egress. This may decrease pneumocephalus, thus decreasing brain shift during implantation. OBJECTIVE: To compare the incidence and volume of pneumocephalus during awake (wkDBS) and aDBS procedures. METHODS: A retrospective review of bilateral DBS cases performed at Oregon Health & Science University from 2009 to 2017 was undertaken. Postimplantation imaging was reviewed to determine the presence and volume of intracranial air and measure cortical brain shift. RESULTS: Among 371 patients, pneumocephalus was noted in 66% of wkDBS and 15.6% of aDBS. The average volume of air was significantly higher in wkDBS than aDBS (8.0 vs. 1.8 mL). Volumes of air greater than 7 mL, which have previously been linked to brain shift, occurred significantly more frequently in wkDBS than aDBS (34 vs 5.6%). wkDBS resulted in significantly larger cortical brain shifts (5.8 vs. 1.2 mm). CONCLUSIONS: We show that aDBS reduces the incidence of intracranial air, larger air volumes, and cortical brain shift. Large volumes of intracranial air have been correlated to shifting of brain structures during DBS procedures, a variable that could impact accuracy of electrode placement.

Navigated 3D-ultrasound versus conventional neuronavigation during awake resections of eloquent low-grade gliomas: a comparative study at a single institution.

BACKGROUND: The data showing usefulness of navigated 3D-ultrasound (3DUS) during awake resections of eloquent gliomas are sparse. Results of surgeries performed using 3DUS were never compared to procedures guided by standard neuronavigation. The aim of this work is to assess the effectiveness of 3DUS during awake resections of eloquent low-grade gliomas (LGGs) by comparing surgical results of two series of patients operated on using conventional neuronavigation and using 3DUS. To our knowledge, a similar study is lacking in the literature. METHODS: During a 4-year period (September 2006 to August 2010) 21 awake resections of LGGs guided by neuronavigation (series 1, S1) were consecutively performed in Department of Neurosurgery in Bratislava. During another 4-year period (August 2010 to July 2014) 28 awake resections of LGGs guided by 3DUS (series 2, S2) were consecutively conducted. In both patients series, the eloquent cortical and subcortical structures were intraoperatively detected by direct electrical stimulation. Extent of tumor resection (EOR) and functional outcome in both series were compared. RESULTS: EOR was significantly greater (p = 0.022) in S2 (median = 93.25%; mean = 86.79%), as compared to S1 (median 87.1%; mean = 75.85%). One permanent minor deficit in S1 and 2 minor deficits in S2 occurred, the difference was not significant (p = 0.999). CONCLUSIONS: Our work represents the first study comparing results of surgeries guided by 3DUS versus conventional navigation. The extent of awake resections of eloquent LGG guided by 3DUS was greater comparing to awake resections guided by standard neuronavigation; use of 3DUS had no impact on the number of new permanent deficits.

Immobile cerebral veins in the context of positional brain shift: an undescribed risk factor for acute subdural hemorrhage.

BACKGROUND: Changes in head position are thought to cause a degree of brain shift in the intracranial cavity. However, little is known on the concurrent shift of the cerebral veins. The present study aimed to investigate the positional shift of the cerebral veins that accompanies brain shift. METHODS: Sagittal T2-weighted magnetic resonance imaging was performed on 21 consecutive patients lying in the supine and prone positions, using the same sequence. For each patient, imaging data were obtained for the two positions as a pair of images with morphologically best-matched cerebral contours. RESULTS: The subarachnoid spaces in the parasagittal frontal convexity showed variable reductions related to a postural change from a supine to a prone position, with a mean percent reduction (%Δ) of 17.8 ± 11.7%. Additionally, cerebral cisterns ventral to the brainstem and upper cervical cord were reduced in most patients when lying in a prone position, with a mean %Δ of 16.6 ± 8.7%. In contrast, none of these 130 pairs of identical venous segments located in the parasagittal cerebral convexity showed positional shift. Cadaveric dissections found that the major cortical veins were superficially upheld by the arachnoid membranes. CONCLUSIONS: The parasagittal major cortical and bridging veins do not seem to show positional shifts. Positional change in the posterior-anterior direction causes a shearing between the frontal cortices and the distributing veins and can be a risk factor for acute subdural hemorrhage, in case of severe head trauma.

Automated alignment of perioperative MRI scans: A technical note and application in pediatric epilepsy surgery.

Conventional image registration utilizing brain voxel information may be erroneous in a neurosurgical setting due to pathology and surgery-related anatomical distortions. We report a novel application of an automated image registration procedure based on skull segmentation for magnetic resonance imaging (MRI) scans acquired before, during and after surgery (i.e., perioperative). The procedure was implemented to assist analysis of intraoperative brain shift in 11 pediatric epilepsy surgery cases, each of whom had up to five consecutive perioperative MRI scans. The procedure consisted of the following steps: (1) Skull segmentation using tissue classification tools. (2) Estimation of rigid body transformation between image pairs using registration driven by the skull segmentation. (3) Composition of transformations to provide transformations between each scan and a common space. The procedure was validated using locations of three types of reference structural landmarks: the skull pin sites, the eye positions, and the scalp skin surface, detected using the peak intensity gradient. The mean target registration error (TRE) scores by skull pin sites and scalp skin rendering were around 1 mm and <1 mm, respectively. Validation by eye position demonstrated >1 mm TRE scores, suggesting it is not a reliable reference landmark in surgical scenarios. Comparable registration accuracy was achieved between opened and closed skull scan pairs and closed and closed skull scan pairs. Our procedure offers a reliable registration framework for processing intrasubject time series perioperative MRI data, with potential of improving intraoperative MRI-based image guidance in neurosurgical practice. Hum Brain Mapp 37:3530-3543, 2016. © 2016 Wiley Periodicals, Inc.

Effect of Cranial Window Diameter During Deep Brain Stimulation Surgery on Volume of Pneumocephalus.

OBJECTIVE: Successful deep brain stimulation (DBS) surgery necessitates high accuracy in targeting specific intracranial nuclei. Brain shift due to pneumocephalus can contribute to decreased accuracy. Larger burr holes and dural openings may increase pneumocephalus volume due to a greater degree of communication between the subdural space and extracranial air. The aim of this study is to determine if there is a statistically and clinically significant difference in postoperative pneumocephalus volume related to burr hole and durotomy size. MATERIALS AND METHODS: DBS electrodes were surgically implanted through either large (14 mm) burr holes or small (4 mm) twist drill holes. Immediate postoperative computerized tomography (CT) scans of 165 electrode implantations in 85 patients from 2010 to 2013 were retrospectively analyzed. Student's t-test and Mann-Whitney U-test were employed with a threshold of significance set at p ≤ 0.05. RESULTS: No significant difference in pneumocephalus was identified between patients who had implantation of DBS electrodes through 4 mm twist drill holes (N = 71 hemispheres, 12.84 ± 9.79 cm(3) ) and those with large 14 mm burr holes (N = 87, 11.70 ± 7.46 cm(3) , p = 0.42). Volume of pneumocephalus did not correlate with duration of surgery or patient age. The groups did not differ significantly with respect to other aspects of surgical implantation technique or surgical duration. CONCLUSION: While identifying factors that may reduce pneumocephalus volume may be critical to improving stereotactic accuracy and targeting, the current results suggest that burr hole size may not alter the degree of brain shift.

Porcine-human glioma xenograft model. Immunosuppression and model reproducibility.

BACKGROUND: Glioblastoma is the most common primary malignant and treatment-resistant human brain tumor. Rodent models have played an important role in understanding brain cancer biology and treatment. However, due to their small cranium and tumor volume mismatch, relative to human disease, they have been less useful for translational studies. Therefore, development of a consistent and simple large animal glioma xenograft model would have significant translational benefits. METHODS: Immunosuppression was induced in twelve standard Yucatan minipigs. 3 pigs received cyclosporine only, while 9 pigs received a combined regimen including cyclosporine (55 mg/kg q12 h), prednisone (25 mg, q24 h) and mycophenolate (500 mg q24 h). U87 cells (2 × 106) were stereotactically implanted into the left frontal cortex. The implanted brains were imaged by MRI for monitoring. In a separate study, tumors were grown in 5 additional pigs using the combined regimen, and pigs underwent tumor resection with intra-operative image updating to determine if the xenograft model could accurately capture the spatial tumor resection challenges seen in humans. RESULTS: Tumors were successfully implanted and grown in 11 pigs. One animal in cyclosporine only group failed to show clinical tumor growth. Clinical tumor growth, assessed by MRI, progressed slowly over the first 10 days, then rapidly over the next 10 days. The average tumor growth latency period was 20 days. Animals were monitored twice daily and detailed records were kept throughout the experimental period. Pigs were sacrificed humanely when the tumor reached 1 - 2 cm. Some pigs experienced decreased appetite and activity, however none required premature euthanasia. In the image updating study, all five pigs demonstrated brain shift after craniotomy, consistent with what is observed in humans. Intraoperative image updating was able to accurately capture and correct for this shift in all five pigs. CONCLUSION: This report demonstrates the development and use of a human intracranial glioma model in an immunosuppressed, but nongenetically modified pig. While the immunosuppression of the model may limit its utility in certain studies, the model does overcome several limitations of small animal or genetically modified models. For instance, we demonstrate use of this model for guiding surgical resection with intraoperative image-updating technologies. We further report use of a surrogate extracranial tumor that indicates growth of the intracranial tumor, allowing for relative growth assessment without radiological imaging.

D2BGAN: Dual Discriminator Bayesian Generative Adversarial Network for Deformable MR-Ultrasound Registration Applied to Brain Shift Compensation.

During neurosurgical procedures, the neuro-navigation system's accuracy is affected by the brain shift phenomenon. One popular strategy is to compensate for brain shift using intraoperative ultrasound (iUS) registration with pre-operative magnetic resonance (MR) scans. This requires a satisfactory multimodal image registration method, which is challenging due to the low image quality of ultrasound and the unpredictable nature of brain deformation during surgery. In this paper, we propose an automatic unsupervised end-to-end MR-iUS registration approach named the Dual Discriminator Bayesian Generative Adversarial Network (D2BGAN). The proposed network consists of two discriminators and a generator optimized by a Bayesian loss function to improve the functionality of the generator, and we add a mutual information loss function to the discriminator for similarity measurements. Extensive validation was performed on the RESECT and BITE datasets, where the mean target registration error (mTRE) of MR-iUS registration using D2BGAN was determined to be 0.75 ± 0.3 mm. The D2BGAN illustrated a clear advantage by achieving an 85% improvement in the mTRE over the initial error. Moreover, the results confirmed that the proposed Bayesian loss function, rather than the typical loss function, improved the accuracy of MR-iUS registration by 23%. The improvement in registration accuracy was further enhanced by the preservation of the intensity and anatomical information of the input images.

Preventing Shift from Pneumocephalus During Deep Brain Stimulation Surgery: Don't Give Up the 'Fork in the Brain'.

Clinical vignette: We present the case of a patient who developed intra-operative pneumocephalus during left globus pallidus internus deep brain stimulation (DBS) placement for Parkinson's disease (PD). Microelectrode recording (MER) revealed that we were anterior and lateral to the intended target. Clinical dilemma: Clinically, we suspected brain shift from pneumocephalus. Removal of the guide-tube for readjustment of the brain target would have resulted in the introduction of movement resulting from brain shift and from displacement from the planned trajectory. Clinical solution: We elected to leave the guide-tube cannula in place and to pass the final DBS lead into a channel that was located posterior-medially from the center microelectrode pass. Gap in knowledge: Surgical techniques which can be employed to minimize brain shift in the operating room setting are critical for reduction in variation of the final DBS lead placement. Pneumocephalus after dural opening is one potential cause of brain shift. The recognition that the removal of a guide-tube cannula could worsen brain shift creates an opportunity for an intraoperative team to maintain the advantage of the 'fork' in the brain provided by the initial procedure's requirement of guide-tube placement.