Yanmei Tie

Non-rectangular waveforms for neural stimulation with practical electrodes

Historically the rectangular pulse waveform has been the choice for neural stimulation. The strength-duration curve is thus defined for rectangular pulses. Not much attention has been paid to alternative waveforms to determine if the pulse shape has an effect on the strength-duration relation. Similarly the charge injection capacity of neural electrodes has also been measured with rectangular pulses. In this study we questioned if non-rectangular waveforms can generate a stronger stimulation effect, when applied through practical electrodes, by minimizing the neural activation threshold and maximizing the charge injection capacity of the electrode. First, the activation threshold parameters were studied with seven different pulse shapes using computer simulations of a local membrane model. These waveforms were rectangular, linear increase and decrease, exponential increase and decrease, Gaussian, and sinusoidal. The chronaxie time was found to be longer with all the non-rectangular pulses and some provided more energy efficient stimulation than the rectangular waveform. Second, the charge injection capacity of titanium nitride microelectrodes was measured experimentally for the same waveforms. Linearly decreasing ramp provided the best charge injection for all pulse widths tested from 0.02 to 0.5 ms. Finally, the most efficient waveform that maximized the charge injection capacity of the electrode while providing the lowest threshold charge for neural activation was searched. Linear and exponential decrease, and Gaussian waveforms were found to be the most efficient pulse shapes.

A combined fMRI and DTI examination of functional language lateralization and arcuate fasciculus structure: Effects of degree versus direction of hand preference

The present study examined the relationship between hand preference degree and direction, functional language lateralization in Brocas and Wernickes areas, and structural measures of the arcuate fasciculus. Results revealed an effect of degree of hand preference on arcuate fasciculus structure, such that consistently-handed individuals, regardless of the direction of hand preference, demonstrated the most asymmetric arcuate fasciculus, with larger left versus right arcuate, as measured by DTI. Functional language lateralization in Wernickes area, measured via fMRI, was related to arcuate fasciculus volume in consistent-left-handers only, and only in people who were not right hemisphere lateralized for language; given the small sample size for this finding, future investigation is warranted. Results suggest handedness degree may be an important variable to investigate in the context of neuroanatomical asymmetries.

Threshold-independent functional MRI determination of language dominance: A validation study against clinical gold standards

Functional MRI (fMRI) is often used for presurgical language lateralization. In the most common approach, a laterality index (LI) is calculated on the basis of suprathreshold voxels. However, strong dependencies between LI and threshold can diminish the effectiveness of this technique; in this study we investigated an original methodology that is independent of threshold. We compared this threshold-independent method against the common threshold-dependent method in 14 patients with epilepsy who underwent Wada testing. In addition, clinical results from electrocortical language mapping and postoperative language findings were used to assess the validity of the fMRI lateralization method. The threshold-dependent methodology yielded ambiguous or incongruent lateralization outcomes in 4 of 14 patients in the inferior frontal gyrus (IFG) and in 6 of 14 patients in the supramarginal gyrus (SMG). Conversely, the threshold-independent method yielded unambiguous lateralization in all the patients tested, and demonstrated lateralization outcomes incongruent with clinical standards in 2 of 14 patients in IFG and in 1 of 14 patients in SMG. This validation study demonstrates that the threshold-dependent LI calculation is prone to significant within-patient variability that could render results unreliable; the threshold-independent method can generate distinct LIs that are more concordant with gold standard clinical findings.

Group independent component analysis of language fMRI from word generation tasks.

Language fMRI has been used to study brain regions involved in language processing and has been applied to pre-surgical language mapping. However, in order to provide clinicians with optimal information, the sensitivity and specificity of language fMRI needs to be improved. Type II error of failing to reach statistical significance when the language activations are genuinely present may be particularly relevant to pre-surgical planning, by falsely indicating low surgical risk in areas where no activations are shown. Furthermore, since the execution of language paradigms involves cognitive processes other than language function per se, the conventional general linear model (GLM) method may identify non-language-specific activations. In this study, we assessed an exploratory approach, independent component analysis (ICA), as a potential complementary method to the inferential GLM method in language mapping applications. We specifically investigated whether this approach might reduce type II error as well as generate more language-specific maps. Fourteen right-handed healthy subjects were studied with fMRI during two word generation tasks. A similarity analysis across tasks was proposed to select components of interest. Union analysis was performed on the language-specific components to increase sensitivity, and conjunction analysis was performed to identify language areas more likely to be essential. Compared with GLM, ICA identified more activated voxels in the putative language areas, and signals from other sources were isolated into different components. Encouraging results from one brain tumor patient are also presented. ICA may be used as a complementary tool to GLM in improving pre-surgical language mapping.

Extended Broca's area in the functional connectome of language in adults: combined cortical and subcortical single-subject analysis using fMRI and DTI tractography.

Traditional models of the human language circuitry encompass three cortical areas, Broca’s, Geschwind’s and Wernicke’s, and their connectivity through white matter fascicles. The neural connectivity deep to these cortical areas remains poorly understood, as does the macroscopic functional organization of the cortico-subcortical language circuitry. In an effort to expand current knowledge, we combined functional MRI (fMRI) and diffusion tensor imaging to explore subject-specific structural and functional macroscopic connectivity, focusing on Broca’s area. Fascicles were studied using diffusion tensor imaging fiber tracking seeded from volumes placed manually within the white matter. White matter fascicles and fMRI-derived clusters (antonym-generation task) of positive and negative blood-oxygen-level-dependent (BOLD) signal were co-registered with 3-D renderings of the brain in 12 healthy subjects. Fascicles connecting BOLD-derived clusters were analyzed within specific cortical areas: Broca’s, with the pars triangularis, the pars opercularis, and the pars orbitaris; Geschwind’s and Wernicke’s; the premotor cortex, the dorsal supplementary motor area, the middle temporal gyrus, the dorsal prefrontal cortex and the frontopolar region. We found a functional connectome divisible into three systems—anterior, superior and inferior—around the insula, more complex than previously thought, particularly with respect to a new extended Broca’s area. The extended Broca’s area involves two new fascicles: the operculo-premotor fascicle comprised of well-organized U-shaped fibers that connect the pars opercularis with the premotor region; and (2) the triangulo-orbitaris system comprised of intermingled U-shaped fibers that connect the pars triangularis with the pars orbitaris. The findings enhance our understanding of language function.

Comparison of blocked and event-related fMRI designs for pre-surgical language mapping

Language functional magnetic resonance imaging (fMRI) is a promising non-invasive technique for pre-surgical planning in patients whose lesions are adjacent to or within critical language areas. Most language fMRI studies in patients use blocked experimental design. In this study, we compared a blocked design and a rapid event-related design with a jittered inter-stimulus-interval (ISI) (or stochastic design) for language fMRI in six healthy controls, and eight brain tumor patients, using a vocalized antonym generation task. Comparisons were based on visual inspection of fMRI activation maps and degree of language lateralization, both of which were assessed at a constant statistical threshold for each design. The results indicated a relatively high degree of discordance between the two task designs. In general, the event-related design provided maps with more robust activations in the putative language areas than the blocked design, especially for brain tumor patients. Our results suggest that the rapid event-related design has potential for providing comparable or even higher detection power over the blocked design for localizing language function in brain tumor patients, and therefore may be able to generate more sensitive language maps. More patient studies, and further investigation and optimization of language fMRI paradigms will be needed to determine the utility and validity of this approach for pre-surgical planning.

Reconstruction of the arcuate fasciculus for surgical planning in the setting of peritumoral edema using two-tensor unscented Kalman filter tractography

Background Diffusion imaging tractography is increasingly used to trace critical fiber tracts in brain tumor patients to reduce the risk of post-operative neurological deficit. However, the effects of peritumoral edema pose a challenge to conventional tractography using the standard diffusion tensor model. The aim of this study was to present a novel technique using a two-tensor unscented Kalman filter (UKF) algorithm to track the arcuate fasciculus (AF) in brain tumor patients with peritumoral edema. Methods Ten right-handed patients with left-sided brain tumors in the vicinity of language-related cortex and evidence of significant peritumoral edema were retrospectively selected for the study. All patients underwent 3-Tesla magnetic resonance imaging (MRI) including a diffusion-weighted dataset with 31 directions. Fiber tractography was performed using both single-tensor streamline and two-tensor UKF tractography. A two-regions-of-interest approach was applied to perform the delineation of the AF. Results from the two different tractography algorithms were compared visually and quantitatively. Results Using single-tensor streamline tractography, the AF appeared disrupted in four patients and contained few fibers in the remaining six patients. Two-tensor UKF tractography delineated an AF that traversed edematous brain areas in all patients. The volume of the AF was significantly larger on two-tensor UKF than on single-tensor streamline tractography (p < 0.01). Conclusions Two-tensor UKF tractography provides the ability to trace a larger volume AF than single-tensor streamline tractography in the setting of peritumoral edema in brain tumor patients.

Intraoperative Magnetic Resonance Imaging in Intracranial Glioma Resection: A Single-Center, Retrospective Blinded Volumetric Study

BACKGROUND Intraoperative magnetic resonance imaging (IoMRI) was devised to overcome brain shifts during craniotomies. Yet, the acceptance of IoMRI is limited. OBJECTIVE To evaluate impact of IoMRI on intracranial glioma resection outcome including overall patient survival. METHODS A retrospective review of records was performed on a cohort of 164 consecutive patients who underwent resection surgery for newly diagnosed intracranial gliomas either with or without IoMRI technology performed by 2 neurosurgeons in our center. Patient follow-up was at least 5 years. Extent of resection (EOR) was calculated using pre- and postoperative contrast-enhanced and T2-weighted MR-images. Adjusted analysis was performed to compare gross total resection (GTR), EOR, permanent surgery-associated neurologic deficit, and overall survival between the 2 groups. RESULTS Overall median EOR was 92.1%, and 97.45% with IoMRI use and 89.9% without IoMRI, with crude (unadjusted) P < 0.005. GTR was achieved in 49.3% of IoMRI cases, versus in only 21.4% of no-IoMRI cases, P < 0.001. GTR achieved was more with the use of IoMRI among gliomas located in both eloquent and noneloquent brain areas, P = 0.017 and <0.001, respectively. Permanent surgery-associated neurologic deficit was not (statistically) more significant with no-IoMRI, P = 0.284 (13.8% vs. 6.7%). In addition, the IoMRI group had better 5-year overall survival, P < 0.001. CONCLUSION This study shows that the use of IoMRI was associated with greater rates of EOR and GTR, and better overall 5-year survival in both eloquent brain areas located and non-eloquent brain areas located gliomas, with no increased risk of neurologic complication.

Corticospinal tract modeling for neurosurgical planning by tracking through regions of peritumoral edema and crossing fibers using two-tensor unscented Kalman filter tractography

PurposeThe aim of this study was to present a tractography algorithm using a two-tensor unscented Kalman filter (UKF) to improve the modeling of the corticospinal tract (CST) by tracking through regions of peritumoral edema and crossing fibers.MethodsTen patients with brain tumors in the vicinity of motor cortex and evidence of significant peritumoral edema were retrospectively selected for the study. All patients underwent 3-T magnetic resonance imaging (MRI) including functional MRI (fMRI) and a diffusion-weighted data set with 31 directions. Fiber tracking was performed using both single-tensor streamline and two-tensor UKF tractography methods. A two-region-of-interest approach was used to delineate the CST. Results from the two tractography methods were compared visually and quantitatively. fMRI was applied to identify the functional fiber tracts.ResultsSingle-tensor streamline tractography underestimated the extent of tracts running through the edematous areas and could only track the medial projections of the CST. In contrast, two-tensor UKF tractography tracked fanning projections of the CST despite peritumoral edema and crossing fibers. Based on visual inspection, the two-tensor UKF tractography delineated tracts that were closer to motor fMRI activations, and it was apparently more sensitive than single-tensor streamline tractography to define the tracts directed to the motor sites. The volume of the CST was significantly larger on two-tensor UKF than on single-tensor streamline tractography (