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Norton, Isaiah Hakim

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Norton

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Isaiah Hakim

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Norton, Isaiah Hakim

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2010 - 201512

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Author's Publications: search.filters.isAuthorOfPublication.cc92e5ae-6942-4ac5-a476-95711a1fc85e

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Now showing 1 - 10 of 12
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    Reconstruction of the arcuate fasciculus for surgical planning in the setting of peritumoral edema using two-tensor unscented Kalman filter tractography
    (Elsevier, 2015) Chen, Zhenrui; Tie, Yanmei; Olubiyi, Olutayo; Rigolo, Laura; Mehrtash, Alireza; Norton, Isaiah Hakim; Pasternak, Ofer; Rathi, Yogesh; Golby, Alexandra; O'Donnell, Lauren
    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.
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    Molecular imaging of drug transit through the blood-brain barrier with MALDI mass spectrometry imaging
    (Nature Publishing Group, 2013) Liu, Xiaohui; Ide, Jennifer L.; Norton, Isaiah Hakim; Marchionni, Mark A.; Ebling, Maritza C.; Wang, Lan; Davis, Erin; Sauvageot, Claire M.; Kesari, Santosh; Kellersberger, Katherine A.; Easterling, Michael L.; Santagata, Sandro; Stuart, Darrin D.; Alberta, John; Agar, Jeffrey N.; Stiles, Charles; Agar, Nathalie Y. R.
    Drug transit through the blood-brain barrier (BBB) is essential for therapeutic responses in malignant glioma. Conventional methods for assessment of BBB penetrance require synthesis of isotopically labeled drug derivatives. Here, we report a new methodology using matrix assisted laser desorption ionization mass spectrometry imaging (MALDI MSI) to visualize drug penetration in brain tissue without molecular labeling. In studies summarized here, we first validate heme as a simple and robust MALDI MSI marker for the lumen of blood vessels in the brain. We go on to provide three examples of how MALDI MSI can provide chemical and biological insights into BBB penetrance and metabolism of small molecule signal transduction inhibitors in the brain – insights that would be difficult or impossible to extract by use of radiolabeled compounds.
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    Development of Stereotactic Mass Spectrometry for Brain Tumor Surgery
    (Oxford University Press (OUP), 2011) Agar, Nathalie; Golby, Alexandra; Ligon, Keith; Norton, Isaiah Hakim; Mohan, Vandana; Wiseman, Justin M; Tannenbaum, Allen; Jolesz, Ferenc
    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.
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    The Fiber Laterality Histogram: A New Way to Measure White Matter Asymmetry
    (Springer Berlin Heidelberg, 2010) O’Donnell, Lauren J.; Westin, Carl-Fredrik; Norton, Isaiah Hakim; Whalen, Stephen; Rigolo, Laura; Propper, Ruth; Golby, Alexandra
    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.
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    Interactive Diffusion Tensor Tractography Visualization for Neurosurgical Planning
    (Oxford University Press (OUP), 2011) Golby, Alexandra; Kindlmann, Gordon; Norton, Isaiah Hakim; Yarmarkovich, Alexander; Pieper, Steven; Kikinis, Ron
    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.
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    Intraoperative Real-Time Querying of White Matter Tracts During Frameless Stereotactic Neuronavigation
    (Oxford University Press (OUP), 2011) Elhawary, Haytham; Liu, Haiying; Patel, Pratik; Norton, Isaiah Hakim; Rigolo, Laura; Papademetris, Xenophon; Hata, Nobuhiko; Golby, Alexandra
    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.
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    Special Surgical Considerations for Functional Brain Mapping
    (Elsevier BV, 2011) Kekhia, Hussein; Rigolo, Laura; Norton, Isaiah Hakim; Golby, Alexandra
    The development of functional mapping techniques gives neurosurgeons many options for preoperative planning. Integrating functional and anatomic data can inform patient selection and surgical planning and makes functional mapping more accessible than when only invasive studies were available. However, the applications of functional mapping to neurosurgical patients are still evolving. Functional imaging remains complex and requires an understanding of the underlying physiologic and imaging characteristics. Neurosurgeons must be accustomed to interpreting highly processed data. Successful implementation of functional image-guided procedures requires efficient interactions between neurosurgeon, neurologist, radiologist, neuropsychologist, and others, but promises to enhance the care of patients.
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    Visual Pathway Study Using In Vivo Diffusion Tensor Imaging Tractography to Complement Classic Anatomy
    (Oxford University Press (OUP), 2012) Wu, Wentao; Rigolo, Laura; O'Donnell, Lauren; Norton, Isaiah Hakim; Shriver, Sargent; Golby, Alexandra
    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.
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    Defining language networks from resting-state fMRI for surgical planning-a feasibility study
    (Wiley-Blackwell, 2013) Tie, Yanmei; Rigolo, Laura; Norton, Isaiah Hakim; Huang, Raymond; Wu, Wentao; Orringer, Daniel; Mukundan, Srinivasan; Golby, Alexandra
    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.
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    Bayesian characterization of uncertainty in intra-subject non-rigid registration
    (Elsevier BV, 2013) Risholm, Petter; Janoos, Firdaus; Norton, Isaiah Hakim; Golby, Alexandra; Wells, William
    In settings where high-level inferences are made based on registered image data, the registration uncertainty can contain important information. In this article, we propose a Bayesian non-rigid registration framework where conventional dissimilarity and regularization energies can be included in the likelihood and the prior distribution on deformations respectively through the use of Boltzmann’s distribution. The posterior distribution is characterized using Markov Chain Monte Carlo (MCMC) methods with the effect of the Boltzmann temperature hyper-parameters marginalized under broad uninformative hyper-prior distributions. The MCMC chain permits estimation of the most likely deformation as well as the associated uncertainty. On synthetic examples, we demonstrate the ability of the method to identify the maximum a posteriori estimate and the associated posterior uncertainty, and demonstrate that the posterior distribution can be non-Gaussian. Additionally, results from registering clinical data acquired during neurosurgery for resection of brain tumor are provided; we compare the method to single transformation results from a deterministic optimizer and introduce methods that summarize the high-dimensional uncertainty. At the site of resection, the registration uncertainty increases and the marginal distribution on deformations is shown to be multi-modal.