Arousal and salience network connectivity alterations in surgical temporal lobe epilepsy.

OBJECTIVE: It is poorly understood why patients with mesial temporal lobe epilepsy (TLE) have cognitive deficits and brain network changes that extend beyond the temporal lobe, including altered extratemporal intrinsic connectivity networks (ICNs). However, subcortical arousal structures project broadly to the neocortex, are affected by TLE, and thus may contribute to these widespread network effects. The authors' objective was to examine functional connectivity (FC) patterns between subcortical arousal structures and neocortical ICNs, possible neurocognitive relationships, and FC changes after epilepsy surgery. METHODS: The authors obtained resting-state functional magnetic resonance imaging (fMRI) in 50 adults with TLE and 50 controls. They compared nondirected FC (correlation) and directed FC (Granger causality laterality index) within the salience network, default mode network, and central executive network, as well as between subcortical arousal structures; these 3 ICNs were also compared between patients and controls. They also used an fMRI-based vigilance index to relate alertness to arousal center FC. Finally, fMRI was repeated in 29 patients > 12 months after temporal lobe resection. RESULTS: Nondirected FC within the salience (p = 0.042) and default mode (p = 0.0008) networks, but not the central executive network (p = 0.79), was decreased in patients in comparison with controls (t-tests, corrected). Nondirected FC between the salience network and subcortical arousal structures (nucleus basalis of Meynert, thalamic centromedian nucleus, and brainstem pedunculopontine nucleus) was reduced in patients in comparison with controls (p = 0.0028-0.015, t-tests, corrected), and some of these connectivity abnormalities were associated with lower processing speed index, verbal comprehension, and full-scale IQ. Interestingly, directed connectivity measures suggested a loss of top-down influence from the salience network to the arousal nuclei in patients. After resection, certain FC patterns between the arousal nuclei and salience network moved toward control values in the patients, suggesting that some postoperative recovery may be possible. Although an fMRI-based vigilance measure suggested that patients exhibited reduced alertness over time, FC abnormalities between the salience network and arousal structures were not influenced by the alertness levels during the scans. CONCLUSIONS: FC abnormalities between subcortical arousal structures and ICNs, such as the salience network, may be related to certain neurocognitive deficits in TLE patients. Although TLE patients demonstrated vigilance abnormalities, baseline FC perturbations between the arousal and salience networks are unlikely to be driven solely by alertness level, and some may improve after surgery. Examination of the arousal network and ICN disturbances may improve our understanding of the downstream clinical effects of TLE.

Temporal lobe epilepsy lateralisation and surgical outcome prediction using diffusion imaging.

OBJECTIVE: We sought to augment the presurgical workup of medically refractory temporal lobe epilepsy by creating a supervised machine learning technique that uses diffusion-weighted imaging to classify patient-specific seizure onset laterality and surgical outcome. METHODS: 151 subjects were included in this analysis: 62 patients (aged 18-68 years, 36 women) and 89 healthy controls (aged 18-71 years, 47 women). We created a supervised machine learning technique that uses diffusion-weighted metrics to classify subject groups. Specifically, we sought to classify patients versus healthy controls, unilateral versus bilateral temporal lobe epilepsy, left versus right temporal lobe epilepsy and seizure-free versus not seizure-free surgical outcome. We then reduced the dimensionality of derived features with community detection for ease of interpretation. RESULTS: We classified the subject groups in withheld testing data sets with a cross-fold average testing areas under the receiver operating characteristic curve of 0.745 for patients versus healthy controls, 1.000 for unilateral versus bilateral seizure onset, 0.662 for left versus right seizure onset, 0.800 for left-sided seizure-free vsersu not seizure-free surgical outcome and 0.775 for right-sided seizure-free versus not seizure-free surgical outcome. CONCLUSIONS: This technique classifies important clinical decisions in the presurgical workup of temporal lobe epilepsy by generating discerning white-matter features. We believe that this work augments existing network connectivity findings in the field by further elucidating important white-matter pathology in temporal lobe epilepsy. We hope that this work contributes to recent efforts aimed at using diffusion imaging as an augmentation to the presurgical workup of this devastating neurological disorder.

Impact of brain shift on neural pathways in deep brain stimulation: a preliminary analysis via multi-physics finite element models.

Objective.The effectiveness of deep brain stimulation (DBS) depends on electrode placement accuracy, which can be compromised by brain shift during surgery. While there have been efforts in assessing the impact of electrode misplacement due to brain shift using preop- and postop-imaging data, such analysis using preop- and intraop-imaging data via biophysical modeling has not been conducted. This work presents a preliminary study that applies a multi-physics analysis framework using finite element biomechanical and bioelectric models to examine the impact of realistic intraoperative shift on neural pathways determined by tractography.Approach.The study examined six patients who had undergone interventional magnetic resonance-guided DBS surgery. The modeling framework utilized a biomechanical approach to update preoperative MR to reflect shift-induced anatomical changes. Using this anatomically deformed image and its undeformed counterpart, bioelectric effects from shifting electrode leads could be simulated and neural activation differences were approximated. Specifically, for each configuration, volume of tissue activation was computed and subsequently used for tractography estimation. Total tract volume and overlapping volume with motor regions as well as connectivity profile were compared. In addition, volumetric overlap between different fiber bundles among configurations was computed and correlated to estimated shift.Main results.The study found deformation-induced differences in tract volume, motor region overlap, and connectivity behavior, suggesting the impact of shift. There is a strong correlation (R= -0.83) between shift from intended target and intended neural pathway recruitment, where at threshold of ∼2.94 mm, intended recruitment completely degrades. The determined threshold is consistent with and provides quantitative support to prior observations and literature that deviations of 2-3 mm are detrimental.Significance.The findings support and advance prior studies and understanding to illustrate the need to account for shift in DBS and the potentiality of computational modeling for estimating influence of shift on neural activation.

People with mesial temporal lobe epilepsy have altered thalamo-occipital brain networks.

While temporal lobe epilepsy (TLE) is a focal epilepsy, previous work demonstrates that TLE causes widespread brain-network disruptions. Impaired visuospatial attention and learning in TLE may be related to thalamic arousal nuclei connectivity. Our prior preliminary work in a smaller patient cohort suggests that patients with TLE demonstrate abnormal functional connectivity between central lateral (CL) thalamic nucleus and medial occipital lobe. Others have shown pulvinar connectivity disturbances in TLE, but it is incompletely understood how TLE affects pulvinar subnuclei. Also, the effects of epilepsy surgery on thalamic functional connectivity remains poorly understood. In this study, we examine the effects of TLE on functional connectivity of two key thalamic arousal-nuclei: lateral pulvinar (PuL) and CL. We evaluate resting-state functional connectivity of the PuL and CL in 40 patients with TLE and 40 controls using fMRI. In 25 patients, postoperative images (>1 year) were also compared with preoperative images. Compared to controls, patients with TLE exhibit loss of normal positive connectivity between PuL and lateral occipital lobe (p < 0.05), and a loss of normal negative connectivity between CL and medial occipital lobe (p < 0.01, paired t-tests). FMRI amplitude of low-frequency fluctuation (ALFF) in TLE trended higher in ipsilateral PuL (p = 0.06), but was lower in the lateral occipital (p < 0.01) and medial occipital lobe in patients versus controls (p < 0.05, paired t-tests). More abnormal ALFF in the ipsilateral lateral occipital lobe is associated with worse preoperative performance on Rey Complex Figure Test Immediate (p < 0.05, r = 0.381) and Delayed scores (p < 0.05, r = 0.413, Pearson's Correlations). After surgery, connectivity between PuL and lateral occipital lobe remains abnormal in patients (p < 0.01), but connectivity between CL and medial occipital lobe improves and is no longer different from control values (p > 0.05, ANOVA, post hoc Fischer's LSD). In conclusion, thalamic arousal nuclei exhibit abnormal connectivity with occipital lobe in TLE, and some connections may improve after surgery. Studying thalamic arousal centers may help explain distal network disturbances in TLE.

Accounting for intraoperative brain shift ascribable to cavity collapse during intracranial tumor resection.

Purpose: For many patients with intracranial tumors, accurate surgical resection is a mainstay of their treatment paradigm. During surgical resection, image guidance is used to aid in localization and resection. Intraoperative brain shift can invalidate these guidance systems. One cause of intraoperative brain shift is cavity collapse due to tumor resection, which will be referred to as "debulking." We developed an imaging-driven finite element model of debulking to create a comprehensive simulation data set to reflect possible intraoperative changes. The objective was to create a method to account for brain shift due to debulking for applications in image-guided neurosurgery. We hypothesized that accounting for tumor debulking in a deformation atlas data framework would improve brain shift predictions, which would enhance image-based surgical guidance. Approach: This was evaluated in a six-patient intracranial tumor resection intraoperative data set. The brain shift deformation atlas data framework consisted of n = 756 simulated deformations to account for effects due to gravity-induced and hyperosmotic drug-induced brain shift, which reflects previous developments. An additional complement of n = 84 deformations involving simulated tumor growth followed by debulking was created to capture observed intraoperative effects not previously included. Results: In five of six patient cases evaluated, inclusion of debulking mechanics improved brain shift correction by capturing global mass effects resulting from the resected tumor. Conclusions: These findings suggest imaging-driven brain shift models used to create a deformation simulation data framework of observed intraoperative events can be used to assist in more accurate image-guided surgical navigation in the brain.

Development and evaluation of a "trackerless" surgical planning and guidance system based on 3D Slicer.

Conventional optical tracking systems use cameras sensitive to near-infrared (NIR) light and NIR illuminated/active-illuminating markers to localize instrumentation and the patient in the operating room (OR) physical space. This technology is widely used within the neurosurgical theater and is a staple in the standard of care for craniotomy planning. To accomplish, planning is largely conducted at the time of the procedure in the OR with the patient in a fixed head orientation. We propose a framework to achieve this in the OR without conventional tracking technology, i.e., a "trackerless" approach. Briefly, we investigate an extension of the 3D Slicer which combines surgical planning and craniotomy designation. While taking advantage of the well-developed 3D Slicer platform, we implement advanced features to aid the neurosurgeon in planning the location of the anticipated craniotomy relative to the preoperatively imaged tumor in a physical-to-virtual setup, and then subsequently aid the true physical procedure by correlating that physical-to-virtual plan with an intraoperative magnetic resonance imaging-to-physical registered field-of-view display. These steps are done such that the craniotomy can be designated without the use of a conventional optical tracking technology. To test this approach, four experienced neurosurgeons performed experiments on five different surgical cases using our 3D Slicer module as well as the conventional procedure for comparison. The results suggest that our planning system provides a simple, cost-efficient, and reliable solution for surgical planning and delivery without the use of conventional tracking technologies. We hypothesize that the combination of this craniotomy planning approach and our past developments in cortical surface registration and deformation tracking using stereo-pair data from the surgical microscope may provide a fundamental realization of an integrated trackerless surgical guidance platform.

Biophysical model-based parameters to classify tumor recurrence from radiation-induced necrosis for brain metastases.

PURPOSE: Stereotactic radiosurgery (SRS) is used for local control treatment of patients with intracranial metastases. As a result of SRS, some patients develop radiation-induced necrosis. Radiographically, radiation-induced necrosis can appear similar to tumor recurrence in magnetic resonance (MR) T1 -weighted contrast-enhanced imaging, T2 -weighted MR imaging, and Fluid-Attenuated Inversion Recovery (FLAIR) MR imaging. Radiographic ambiguities often necessitate invasive brain biopsies to determine lesion etiology or cause delayed subsequent therapy initiation. We use a biomechanically coupled tumor growth model to estimate patient-specific model parameters and model-derived measures to noninvasively classify etiology of enhancing lesions in this patient population. METHODS: In this initial, preliminary retrospective study, we evaluated five patients with tumor recurrence and five with radiation-induced necrosis. Longitudinal patient-specific MR imaging data were used in conjunction with the model to parameterize tumor cell proliferation rate and tumor cell diffusion coefficient, and Dice correlation coefficients were used to quantify degree of correlation between model-estimated mechanical stress fields and edema visualized from MR imaging. RESULTS: Results found four statistically relevant parameters which can differentiate tumor recurrence and radiation-induced necrosis. CONCLUSIONS: This preliminary investigation suggests potential of this framework to noninvasively determine the etiology of enhancing lesions in patients who previously underwent SRS for intracranial metastases.

Stereovision-based integrated system for point cloud reconstruction and simulated brain shift validation.

Intraoperative soft tissue deformation, referred to as brain shift, compromises the application of current image-guided surgery navigation systems in neurosurgery. A computational model driven by sparse data has been proposed as a cost-effective method to compensate for cortical surface and volumetric displacements. We present a mock environment developed to acquire stereoimages from a tracked operating microscope and to reconstruct three-dimensional point clouds from these images. A reconstruction error of 1 mm is estimated by using a phantom with a known geometry and independently measured deformation extent. The microscope is tracked via an attached tracking rigid body that facilitates the recording of the position of the microscope via a commercial optical tracking system as it moves during the procedure. Point clouds, reconstructed under different microscope positions, are registered into the same space to compute the feature displacements. Using our mock craniotomy device, realistic cortical deformations are generated. When comparing our tracked microscope stereo-pair measure of mock vessel displacements to that of the measurement determined by the independent optically tracked stylus marking, the displacement error was [Formula: see text] on average. These results demonstrate the practicality of using tracked stereoscopic microscope as an alternative to laser range scanners to collect sufficient intraoperative information for brain shift correction.