Thalamic arousal network disturbances in temporal lobe epilepsy and improvement after surgery.

OBJECTIVE: The effects of temporal lobe epilepsy (TLE) on subcortical arousal structures remain incompletely understood. Here, we evaluate thalamic arousal network functional connectivity in TLE and examine changes after epilepsy surgery. METHODS: We examined 26 adult patients with TLE and 26 matched control participants and used resting-state functional MRI (fMRI) to measure functional connectivity between the thalamus (entire thalamus and 19 bilateral thalamic nuclei) and both neocortex and brainstem ascending reticular activating system (ARAS) nuclei. Postoperative imaging was completed for 19 patients >1 year after surgery and compared with preoperative baseline. RESULTS: Before surgery, patients with TLE demonstrated abnormal thalamo-occipital functional connectivity, losing the normal negative fMRI correlation between the intralaminar central lateral (CL) nucleus and medial occipital lobe seen in controls (p < 0.001, paired t-test). Patients also had abnormal connectivity between ARAS and CL, lower ipsilateral intrathalamic connectivity, and smaller ipsilateral thalamic volume compared with controls (p < 0.05 for each, paired t-tests). Abnormal brainstem-thalamic connectivity was associated with impaired visuospatial attention (ρ = -0.50, p = 0.02, Spearman's rho) while lower intrathalamic connectivity and volume were related to higher frequency of consciousness-sparing seizures (p < 0.02, Spearman's rho). After epilepsy surgery, patients with improved seizures showed partial recovery of thalamo-occipital and brainstem-thalamic connectivity, with values more closely resembling controls (p < 0.01 for each, analysis of variance). CONCLUSIONS: Overall, patients with TLE demonstrate impaired connectivity in thalamic arousal networks that may be involved in visuospatial attention, but these disturbances may partially recover after successful epilepsy surgery. Thalamic arousal network dysfunction may contribute to morbidity in TLE.

Effects of surgical targeting in laser interstitial thermal therapy for mesial temporal lobe epilepsy: A multicenter study of 234 patients.

OBJECTIVE: Laser interstitial thermal therapy (LITT) for mesial temporal lobe epilepsy (mTLE) has reported seizure freedom rates between 36% and 78% with at least 1 year of follow-up. Unfortunately, the lack of robust methods capable of incorporating the inherent variability of patient anatomy, the variability of the ablated volumes, and clinical outcomes have limited three-dimensional quantitative analysis of surgical targeting and its impact on seizure outcomes. We therefore aimed to leverage a novel image-based methodology for normalizing surgical therapies across a large multicenter cohort to quantify the effects of surgical targeting on seizure outcomes in LITT for mTLE. METHODS: This multicenter, retrospective cohort study included 234 patients from 11 centers who underwent LITT for mTLE. To investigate therapy location, all ablation cavities were manually traced on postoperative magnetic resonance imaging (MRI), which were subsequently nonlinearly normalized to a common atlas space. The association of clinical variables and ablation location to seizure outcome was calculated using multivariate regression and Bayesian models, respectively. RESULTS: Ablations including more anterior, medial, and inferior temporal lobe structures, which involved greater amygdalar volume, were more likely to be associated with Engel class I outcomes. At both 1 and 2 years after LITT, 58.0% achieved Engel I outcomes. A history of bilateral tonic-clonic seizures decreased chances of Engel I outcome. Radiographic hippocampal sclerosis was not associated with seizure outcome. SIGNIFICANCE: LITT is a viable treatment for mTLE in patients who have been properly evaluated at a comprehensive epilepsy center. Consideration of surgical factors is imperative to the complete assessment of LITT. Based on our model, ablations must prioritize the amygdala and also include the hippocampal head, parahippocampal gyrus, and rhinal cortices to maximize chances of seizure freedom. Extending the ablation posteriorly has diminishing returns. Further work is necessary to refine this analysis and define the minimal zone of ablation necessary for seizure control.

Structural and functional connectivity of the nondecussating dentato-rubro-thalamic tract.

The dentato-rubro-thalamic tract (DRTT) regulates motor control, connecting the cerebellum to the thalamus. This tract is modulated by deep-brain stimulation in the surgical treatment of medically refractory tremor, especially in essential tremor, where high-frequency stimulation of the thalamus can improve symptoms. The DRTT is classically described as a decussating pathway, ascending to the contralateral thalamus. However, the existence of a nondecussating (i.e. ipsilateral) DRTT in humans was recently demonstrated, and these tracts are arranged in distinct regions of the superior cerebellar peduncle. We hypothesized that the ipsilateral DRTT is connected to specific thalamic nuclei and therefore may have unique functional relevance. The goals of this study were to confirm the presence of the decussating and nondecussating DRTT pathways, identify thalamic termination zones of each tract, and compare whether structural connectivity findings agree with functional connectivity. Diffusion-weighted imaging was used to perform probabilistic tractography of the decussating and nondecussating DRTT in young healthy subjects from the Human Connectome Project (n = 91) scanned using multi-shell diffusion-weighted imaging (270 directions; TR/TE = 5500/89 ms; spatial resolution = 1.25 mm isotropic). To define thalamic anatomical landmarks, a segmentation procedure based on the Morel Atlas was employed, and DRTT targeting was quantified based on the proportion of streamlines arriving at each nucleus. In parallel, functional connectivity analysis was performed using resting-state functional MRI (TR/TE = 720/33 ms; spatial resolution = 2 mm isotropic). It was found that the decussating and nondecussating DRTTs have significantly different thalamic endpoints, with the former preferentially targeting relatively anterior and lateral thalamic nuclei, and the latter connected to more posterior and medial nuclei (p < 0.001). Functional and structural connectivity measures were found to be significantly correlated (r = 0.45, p = 0.031). These findings provide new insight into pathways through which unilateral cerebellum can exert bilateral influence on movement and raise questions about the functional implications of ipsilateral cerebellar efferents.

Atlas-based Segmentation of Intracochlear Anatomy in Metal Artifact Affected CT Images of the Ear with Co-trained Deep Neural Networks.

We propose an atlas-based method to segment the intracochlear anatomy (ICA) in the post-implantation CT (Post-CT) images of cochlear implant (CI) recipients that preserves the point-to-point correspondence between the meshes in the atlas and the segmented volumes. To solve this problem, which is challenging because of the strong artifacts produced by the implant, we use a pair of co-trained deep networks that generate dense deformation fields (DDFs) in opposite directions. One network is tasked with registering an atlas image to the Post-CT images and the other network is tasked with registering the Post-CT images to the atlas image. The networks are trained using loss functions based on voxel-wise labels, image content, fiducial registration error, and cycle-consistency constraint. The segmentation of the ICA in the Post-CT images is subsequently obtained by transferring the predefined segmentation meshes of the ICA in the atlas image to the Post-CT images using the corresponding DDFs generated by the trained registration networks. Our model can learn the underlying geometric features of the ICA even though they are obscured by the metal artifacts. We show that our end-to-end network produces results that are comparable to the current state of the art (SOTA) that relies on a two-steps approach that first uses conditional generative adversarial networks to synthesize artifact-free images from the Post-CT images and then uses an active shape model-based method to segment the ICA in the synthetic images. Our method requires a fraction of the time needed by the SOTA, which is important for end-user acceptance.

Insertion Depth for Optimized Positioning of Precurved Cochlear Implant Electrodes.

HYPOTHESIS: Generic guidelines for insertion depth of precurved electrodes are suboptimal for many individuals. BACKGROUND: Insertion depths that are too shallow result in decreased cochlear coverage, and ones that are too deep lift electrodes away from the modiolus and degrade the electro-neural interface. Guidelines for insertion depth are generically applied to all individuals using insertion depth markers on the array that can be referenced against anatomical landmarks. METHODS: To normalize our measurements, we determined the optimal position and insertion vector where a precurved array best fits the cochlea for each patient in an IRB-approved, N = 131 subject CT database. The distances from the most basal electrode on an optimally placed array to anatomical landmarks, including the round window (RW) and facial recess (FR), was measured for all patients. RESULTS: The standard deviations of the distance from the most basal electrode to the FR and RW are 0.65 mm and 0.26 mm, respectively. Owing to the high variability in FR distance, using the FR as a landmark to determine insertion depth results in >0.5 mm difference with ideal depth in 44% of cases. Alignment of either of the two most proximal RW markers with the RW would result in over-insertion failures for >80% of cases, whereas the use of the third, most medial marker would result in under-insertion in only 19% of cases. CONCLUSIONS: Normalized measurements using the optimized insertion vector show low variance in distance from the basal electrode position to the RW, thereby suggesting it as a better landmark for determining insertion depth than the FR.

Automatic graph-based method for localization of cochlear implant electrode arrays in clinical CT with sub-voxel accuracy.

Cochlear implants (CIs) are neural prosthetics that provide a sense of sound to people who experience severe to profound hearing loss. Recent studies have demonstrated a correlation between hearing outcomes and intra-cochlear locations of CI electrodes. Our group has been conducting investigations on this correlation and has been developing an image-guided cochlear implant programming (IGCIP) system to program CI devices to improve hearing outcomes. One crucial step that has not been automated in IGCIP is the localization of CI electrodes in clinical CTs. Existing methods for CI electrode localization do not generalize well on large-scale datasets of clinical CTs implanted with different brands of CI arrays. In this paper, we propose a novel method for localizing different brands of CI electrodes in clinical CTs. We firstly generate the candidate electrode positions at sub-voxel resolution in a whole head CT by thresholding an up-sampled feature image and voxel-thinning the result. Then, we use a graph-based path-finding algorithm to find a fixed-length path that consists of a subset of the candidates as the localization result. Validation on a large-scale dataset of clinical CTs shows that our proposed method outperforms the state-of-art CI electrode localization methods and achieves a mean error of 0.12 mm when compared to expert manual localization results. This represents a crucial step in translating IGCIP from the laboratory to large-scale clinical use.

Further Evidence of the Relationship Between Cochlear Implant Electrode Positioning and Hearing Outcomes.

BACKGROUND: Postoperative imaging studies by numerous groups have revealed that final cochlear implant (CI) electrode position impacts audiological outcomes with scalar location consistently shown to be a significant factor. Modiolar proximity has been less extensively studied, and findings regarding the effect of insertion depth have been inconsistent. METHODS: Using previously developed automated algorithms, we determined CI electrode position in an Institutional Review Board-approved database of 220 CI ears. Generalized linear models (GLM) were used to analyze the relationship between audiological outcomes and factors including age, duration of CI use, device type, and electrode position. RESULTS: For precurved arrays, GLM revealed that scalar position, modiolar proximity, base insertion depth, and sex were significant factors for Consonant-Nucleus-Consonant (CNC) words (R = 0.43, p < 0.001, n = 92 arrays), while scalar position, modiolar proximity, age, and postlingual onset of deafness were significant for Bamford-Kawal-Bench Sentences in Noise (BKB-SIN) (R = 0.51, p < 0.001, n = 85) scores. Other factors were not significant in the final model after controlling for these variables. For straight arrays, we found the insertion depth, postlingual deafness, and length of CI use to be highly significant (R = 0.47, p < 0.001) factors for CNC words (91 arrays), while for BKB-SIN scores the most significant (R = 0.47, p < 0.001) factors were insertion depth, younger age, and postlingual deafness (89 arrays). CONCLUSION: Our results confirm the significance of electrode positioning in audiological outcomes. The most significant positional predictors of outcome for precurved arrays were full scala tympani (ST) insertion and the modiolar distance, while for the lateral wall arrays the depth of insertion was the most significant factor.

A Structural Connectivity Approach to Validate a Model-based Technique for the Segmentation of the Pulvinar Complex.

The pulvinar of the thalamus is a higher-order thalamic nucleus that is responsible for gating information flow to the cortical regions of the brain. It is involved in several cortico-thalamocortical relay circuits and is known to be affected in a number of neurological disorders. Segmenting the pulvinar in clinically acquired images is important to support studies exploring its role in brain function. In recent years, we have proposed an active shape model method to segment multiple thalamic nuclei, including the pulvinar. The model was created by manual delineation of high resolution 7T images and the process was guided by the Morel stereotactic atlas. However, this model is based on a small library of healthy subjects, and it is important to validate the reliability of the segmentation method on a larger population of clinically acquired images. The pulvinar is known to have particularly strong white matter connections to the hippocampus, which allows us to identify the pulvinar from thalamic regions of high hippocampal structural connectivity. In this study, we obtained T1-weighted and diffusion MR data from 43 healthy volunteers using a clinical 3T MRI scanner. We applied the segmentation method to the T1-weighted images to obtain the intrathalamic nuclei, and we calculated the connectivity maps between the hippocampus and thalamus using the diffusion images. Our results show that the shape model segmentation consistently localizes the pulvinar in the region with the highest hippocampal connectivity. The proposed method can be extended to other nuclei to further validate our segmentation method.

Cochlear implant phantom for evaluating computed tomography acquisition parameters.

Cochlear implants (CIs) are surgically implantable neuroprosthetic devices used to treat profound hearing loss. Recent literature indicates that there is a correlation between the final intracochlear positioning of the CI electrode arrays and the ultimate hearing outcome of the patient, indicating that further studies to better understand the relationship between electrode position and outcomes could have significant implications for future surgical techniques, array design, and processor programming methods. Postimplantation high-resolution computed tomography (CT) imaging is the best modality for localizing electrodes and provides the resolution necessary to visually identify electrode position, although with an unknown degree of accuracy depending on image acquisition parameters, like the hounsfield unit (HU) range of reconstruction, orientation, radiation dose, and image resolution. We report on the development of a phantom and on its use to study how four acquisition parameters, including image resolution and HU range of reconstruction, affect how accurately the true position of the electrodes can be found in a dataset of CT scans acquired from multiple helical and cone beam scanners. We also show how the phantom can be used to evaluate the effect of acquisition parameters on automatic electrode localization techniques.

Correlation of Superior Canal Dehiscence Surface Area With Vestibular Evoked Myogenic Potentials, Audiometric Thresholds, and Dizziness Handicap.

OBJECTIVE: To correlate objective measures of vestibular and audiometric function as well as subjective measures of dizziness handicap with the surface area of the superior canal dehiscence (SCD). STUDY DESIGN: Retrospective chart review and radiological analysis. SETTING: Single tertiary academic referral center. PATIENTS: Preoperative computed tomography imaging, patient survey, audiometric thresholds, and vestibular evoked myogenic potential (VEMP) testing in patients with confirmed SCD. INTERVENTION(S): Image analysis techniques were developed to measure the surface area of each SCD in computed tomography imaging. MAIN OUTCOME MEASURE(S): Preoperative ocular and cervical VEMPs, air and bone conduction thresholds, air-bone gap, dizziness handicap inventory scores, and surface area of the SCD. RESULTS: Fifty-three patients (mean age 52.7 yr) with 84 SCD were analyzed. The median surface area of dehiscence was 1.44 mm (0.068-8.23 mm). Ocular VEMP amplitudes (r = 0.61, p <0.0001), cervical VEMP amplitudes (r = 0.62, p <0.0001), air conduction thresholds at 250 Hz (r = 0.25, p = 0.043), and air-bone gap at 500 Hz (r = 0.27, p = 0.01) positively correlated with increasing size of dehiscence. An inverse relationship between cervical VEMP thresholds (r = -0.56, p < 0.0001) and surface area of the dehiscence was observed. No association between dizziness handicap and surface area was identified. CONCLUSION: Among patients with confirmed SCD, ocular and cervical VEMP amplitudes, cervical VEMP thresholds, and air conduction thresholds at 250 Hz are significantly correlated with the surface area of the dehiscence.