Person:

Golby, Alexandra

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.

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.

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.

BACKGROUND: Surgery remains the first and most important treatment modality for the majority of solid tumors. Across a range of brain tumor types and grades, postoperative residual tumor has a great impact on prognosis. The principal challenge and objective of neurosurgical intervention is therefore to maximize tumor resection while minimizing the potential for neurological deficit by preserving critical tissue. OBJECTIVE: To introduce the integration of desorption electrospray ionization mass spectrometry into surgery for in vivo molecular tissue characterization and intraoperative definition of tumor boundaries without systemic injection of contrast agents. METHODS: Using a frameless stereotactic sampling approach and by integrating a 3-dimensional navigation system with an ultrasonic surgical probe, we obtained image-registered surgical specimens. The samples were analyzed with ambient desorption/ionization mass spectrometry and validated against standard histopathology. This new approach will enable neurosurgeons to detect tumor infiltration of the normal brain intraoperatively with mass spectrometry and to obtain spatially resolved molecular tissue characterization without any exogenous agent and with high sensitivity and specificity. RESULTS: Proof of concept is presented in using mass spectrometry intraoperatively for real-time measurement of molecular structure and using that tissue characterization method to detect tumor boundaries. Multiple sampling sites within the tumor mass were defined for a patient with a recurrent left frontal oligodendroglioma, World Health Organization grade II with chromosome 1p/19q codeletion, and mass spectrometry data indicated a correlation between lipid constitution and tumor cell prevalence. CONCLUSION: The mass spectrometry measurements reflect a complex molecular structure and are integrated with frameless stereotaxy and imaging, providing 3-dimensional molecular imaging without systemic injection of any agents, which can be implemented for surgical margins delineation of any organ and with a rapidity that allows real-time analysis.

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.

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.

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.

BACKGROUND: Change detection is a critical component in the diagnosis and monitoring of many slowly evolving pathologies. OBJECTIVE: This article describes a semiautomatic monitoring approach using longitudinal medical images. We test the method on brain scans of patients with meningioma, which experts have found difficult to monitor because the tumor evolution is very slow and may be obscured by artifacts related to image acquisition. METHODS: We describe a semiautomatic procedure targeted toward identifying difficult-to-detect changes in brain tumor imaging. The tool combines input from a medical expert with state-of-the-art technology. The software is easy to calibrate and, in less than 5 minutes, returns the total volume of tumor change in mm. We test the method on postgadolinium, T1-weighted magnetic resonance images of 10 patients with meningioma and compare our results with experts' findings. We also perform benchmark testing with synthetic data. RESULTS: Our experiments indicated that experts' visual inspections are not sensitive enough to detect subtle growth. Measurements based on experts' manual segmentations were highly accurate but also labor intensive. The accuracy of our approach was comparable to the experts' results. However, our approach required far less user input and generated more consistent measurements. CONCLUSION: The sensitivity of experts' visual inspection is often too low to detect subtle growth of meningiomas from longitudinal scans. Measurements based on experts' segmentation are highly accurate but generally too labor intensive for standard clinical settings. We described an alternative metric that provides accurate and robust measurements of subtle tumor changes while requiring a minimal amount of user input.

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.

Image registration is the process of transforming images acquired at different time points, or with different imaging modalities, into the same coordinate system. It is an essential part of any neurosurgical planning and navigation system because it facilitates combining images with important complementary, structural, and functional information to improve the information based on which a surgeon makes critical decisions. Brigham and Women's Hospital (BWH) has been one of the pioneers in developing intraoperative registration methods for aligning preoperative and intraoperative images of the brain. This article presents an overview of intraoperative registration and highlights some recent developments at BWH.