PTFOS: Flexible and Absorbable Intracranial Electrodes for Magnetic Resonance Imaging

Intracranial electrocortical recording and stimulation can provide unique knowledge about functional brain anatomy in patients undergoing brain surgery. This approach is commonly used in the treatment of medically refractory epilepsy. However, it can be very difficult to integrate the results of cortical recordings with other brain mapping modalities, particularly functional magnetic resonance imaging (fMRI). The ability to integrate imaging and electrophysiological information with simultaneous subdural electrocortical recording/stimulation and fMRI could offer significant insight for cognitive and systems neuroscience as well as for clinical neurology, particularly for patients with epilepsy or functional disorders. However, standard subdural electrodes cause significant artifact in MRI images, and concerns about risks such as cortical heating have generally precluded obtaining MRI in patients with implanted electrodes. We propose an electrode set based on polymer thick film organic substrate (PTFOS), an organic absorbable, flexible and stretchable electrode grid for intracranial use. These new types of MRI transparent intracranial electrodes are based on nano-particle ink technology that builds on our earlier development of an EEG/fMRI electrode set for scalp recording. The development of MRI-compatible recording/stimulation electrodes with a very thin profile could allow functional mapping at the individual subject level of the underlying feedback and feed forward networks. The thin flexible substrate would allow the electrodes to optimally contact the convoluted brain surface. Performance properties of the PTFOS were assessed by MRI measurements, finite difference time domain (FDTD) simulations, micro-volt recording, and injecting currents using standard electrocortical stimulation in phantoms. In contrast to the large artifacts exhibited with standard electrode sets, the PTFOS exhibited no artifact due to the reduced amount of metal and conductivity of the electrode/trace ink and had similar electrical properties to a standard subdural electrode set. The enhanced image quality could enable routine MRI exams of patients with intracranial electrode implantation and could also lead to chronic implantation solutions

Development of a Clinical Functional Magnetic Resonance Imaging Service

One of the limitations of anatomical based imaging approaches is its relative inability to identify whether specific brain functions may be compromised by the location of brain lesions or contemplated brain surgeries. For this reason, methods for identifying the regions of eloquent brain that should not be disturbed are absolutely critical to the surgeon. By accurately identifying these regions preoperatively, virtually every pre-surgical decision from the surgical approach, operative goals (biopsy, sub-total vs. gross-total resection), and the potential need for awake craniotomy with intraoperative cortical-mapping is affected. Of the many techniques available to the surgeon, functional magnetic resonance imaging (fMRI) has become the primary modality of choice due to the ability of MRI to serve as a “one-stop shop” for assessing both anatomy and functionality of the brain. Given their prevalence, brain tumors serve as the model pathology for the included discussion; however, a similar case can be made for the use of fMRI in other neurological conditions, most notably epilepsy. The value of fMRI was validated in 2007 when the Centers for Medicare and Medicaid Services (CMS) established three new current procedural terminology (CPT) codes for clinical fMRI based upon its use for pre-therapeutic planning. In this article we will discuss the specific requirements for establishing an fMRI program, including specific software and hardware requirements. In addition, the nature of the fMRI CPT codes will be discussed

GBM Volumetry using the 3D Slicer Medical Image Computing Platform

Volumetric change in glioblastoma multiforme (GBM) over time is a critical factor in treatment decisions. Typically, the tumor volume is computed on a slice-by-slice basis using MRI scans obtained at regular intervals. (3D)Slicer – a free platform for biomedical research – provides an alternative to this manual slice-by-slice segmentation process, which is significantly faster and requires less user interaction. In this study, 4 physicians segmented GBMs in 10 patients, once using the competitive region-growing based GrowCut segmentation module of Slicer, and once purely by drawing boundaries completely manually on a slice-by-slice basis. Furthermore, we provide a variability analysis for three physicians for 12 GBMs. The time required for GrowCut segmentation was on an average 61% of the time required for a pure manual segmentation. A comparison of Slicer-based segmentation with manual slice-by-slice segmentation resulted in a Dice Similarity Coefficient of 88.43 ± 5.23% and a Hausdorff Distance of 2.32 ± 5.23 mm

Visual Pathway Study Using In Vivo Diffusion Tensor Imaging Tractography to Complement Classic Anatomy

BACKGROUND: Knowledge of the individual course of the optic radiations (ORs) is important to avoid postoperative visual deficits. Cadaveric studies of the visual pathways are limited because it has not been possible to separate the OR from neighboring tracts accurately and results may not apply to individual patients. Diffusion tensor imaging studies may be able to demonstrate the relationships between the OR and neighboring fibers in vivo in individual subjects. OBJECTIVE: To use diffusion tensor imaging tractography to study the OR and the Meyer loop (ML) anatomy in vivo. METHODS: Ten healthy subjects underwent magnetic resonance imaging with diffusion imaging at 3 T. With the use of a fiducial-based diffusion tensor imaging tractography tool (Slicer 3.3), seeds were placed near the lateral geniculate nucleus to reconstruct individual visual pathways and neighboring tracts. Projections of the ORs onto 3-dimensional brain models were shown individually to quantify relationships to key landmarks. RESULTS: Two patterns of visual pathways were found. The OR ran more commonly deep in the whole superior and middle temporal gyri and superior temporal sulcus. The OR was closely surrounded in all cases by an inferior longitudinal fascicle and a parieto/occipito/temporo-pontine fascicle. The mean left and right distances between the tip of the OR and temporal pole were 39.8 ± 3.8 and 40.6 ± 5.7 mm, respectively. CONCLUSION: Diffusion tensor imaging tractography provides a practical complementary method to study the OR and the Meyer loop anatomy in vivo with reference to individual 3-dimensional brain anatomy

Interactive Diffusion Tensor Tractography Visualization for Neurosurgical Planning

BACKGROUND: Diffusion tensor imaging (DTI) infers the trajectory and location of large white matter tracts by measuring the anisotropic diffusion of water. DTI data may then be analyzed and presented as tractography for visualization of the tracts in 3 dimensions. Despite the important information contained in tractography images, usefulness for neurosurgical planning has been limited by the inability to define which are critical structures within the mass of demonstrated fibers and to clarify their relationship to the tumor. OBJECTIVE: To develop a method to allow the interactive querying of tractography data sets for surgical planning and to provide a working software package for the research community. METHODS: The tool was implemented within an open source software project. Echo-planar DTI at 3 T was performed on 5 patients, followed by tensor calculation. Software was developed that allowed the placement of a dynamic seed point for local selection of fibers and for fiber display around a segmented structure, both with tunable parameters. A neurosurgeon was trained in the use of software in < 1 hour and used it to review cases. RESULTS: Tracts near tumor and critical structures were interactively visualized in 3 dimensions to determine spatial relationships to lesion. Tracts were selected using 3 methods: anatomical and functional magnetic resonance imaging-defined regions of interest, distance from the segmented tumor volume, and dynamic seed-point spheres. CONCLUSION: Interactive tractography successfully enabled inspection of white matter structures that were in proximity to lesions, critical structures, and functional cortical areas, allowing the surgeon to explore the relationships between them

Intraoperative Real-Time Querying of White Matter Tracts During Frameless Stereotactic Neuronavigation

BACKGROUND: Brain surgery faces important challenges when trying to achieve maximum tumor resection while avoiding postoperative neurological deficits. OBJECTIVE: For surgeons to have optimal intraoperative information concerning white matter (WM) anatomy, we developed a platform that allows the intraoperative real-time querying of tractography data sets during frameless stereotactic neuronavigation. METHODS: Structural magnetic resonance imaging, functional magnetic resonance imaging, and diffusion tensor imaging were performed on 5 patients before they underwent lesion resection using neuronavigation. During the procedure, the tracked surgical tool tip position was transferred from the navigation system to the 3-dimensional Slicer software package, which used this position to seed the WM tracts around the tool tip location, rendering a geometric visualization of these tracts on the preoperative images previously loaded onto the navigation system. The clinical feasibility of this approach was evaluated in 5 cases of lesion resection. In addition, system performance was evaluated by measuring the latency between surgical tool tracking and visualization of the seeded WM tracts. RESULTS: Lesion resection was performed successfully in all 5 patients. The seeded WM tracts close to the lesion and other critical structures, as defined by the functional and structural images, were interactively visualized during the intervention to determine their spatial relationships relative to the lesion and critical cortical areas. Latency between tracking and visualization of tracts was less than a second for a fiducial radius size of 4 to 5 mm. CONCLUSION: Interactive tractography can provide an intuitive way to inspect critical WM tracts in the vicinity of the surgical region, allowing the surgeon to have increased intraoperative WM information to execute the planned surgical resection

The Fiber Laterality Histogram: A New Way to Measure White Matter Asymmetry

The quantification of brain asymmetries may provide biomarkers for presurgical localization of language function and can improve our understanding of neural structure-function relationships in health and disease. We propose a new method for studying the asymmetry of the white matter tracts in the entire brain, and we apply it to a preliminary study of normal subjects across the handedness spectrum. Methods for quantifying white matter asymmetry using diffusion MRI tractography have thus far been based on comparing numbers of fibers or volumes of a single fiber tract across hemispheres. We propose a generalization of such methods, where the “number of fibers” laterality measurement is extended to the entire brain using a soft fiber comparison metric. We summarize the distribution of fiber laterality indices over the whole brain in a histogram, and we measure properties of the distribution such as its skewness, median, and inter-quartile range. The whole-brain fiber laterality histogram can be measured in an exploratory fashion without hypothesizing asymmetries only in particular structures. We demonstrate an overall difference in white matter asymmetry in consistent- and inconsistent-handers: the skewness of the fiber laterality histogram is significantly different across handedness groups

Defining language networks from resting-state fMRI for surgical planning-a feasibility study

Presurgical language mapping for patients with lesions close to language areas is critical to neurosurgical decision-making for preservation of language function. As a clinical noninvasive imaging technique, functional MRI (fMRI) is used to identify language areas by measuring blood-oxygen-level dependent (BOLD) signal change while patients perform carefully timed language vs. control tasks. This task-based fMRI critically depends on task performance, excluding many patients who have difficulty performing language tasks due to neurologic deficits. On the basis of recent discovery of resting-state fMRI (rs-fMRI), we propose a “task-free” paradigm acquiring fMRI data when patients simply are at rest. This paradigm is less demanding for patients to perform and easier for technologists to administer. We investigated the feasibility of this approach in right-handed healthy control subjects. First, group independent component analysis (ICA) was applied on the training group (14 subjects) to identify group level language components based on expert rating results. Then, four empirically and structurally defined language network templates were assessed for their ability to identify language components from individuals' ICA output of the testing group (18 subjects) based on spatial similarity analysis. Results suggest that it is feasible to extract language activations from rs-fMRI at the individual subject level, and two empirically defined templates (that focuses on frontal language areas and that incorporates both frontal and temporal language areas) demonstrated the best performance. We propose a semi-automated language component identification procedure and discuss the practical concerns and suggestions for this approach to be used in clinical fMRI language mapping

Rapid, Label-Free Detection of Brain Tumors with Stimulated Raman Scattering Microscopy

Surgery is an essential component in the treatment of brain tumors. However, delineating tumor from normal brain remains a major challenge. We describe the use of stimulated Raman scattering (SRS) microscopy for differentiating healthy human and mouse brain tissue from tumor-infiltrated brain based on histoarchitectural and biochemical differences. Unlike traditional histopathology, SRS is a label-free technique that can be rapidly performed in situ. SRS microscopy was able to differentiate tumor from nonneoplastic tissue in an infiltrative human glioblastoma xenograft mouse model based on their different Raman spectra. We further demonstrated a correlation between SRS and hematoxylin and eosin microscopy for detection of glioma infiltration (κ = 0.98). Finally, we applied SRS microscopy in vivo in mice during surgery to reveal tumor margins that were undetectable under standard operative conditions. By providing rapid intraoperative assessment of brain tissue, SRS microscopy may ultimately improve the safety and accuracy of surgeries where tumor boundaries are visually indistinct.Chemistry and Chemical Biolog