Publications by Year: 2011

Tina Kapur, Clare M. Tempany, and Ferenc A. Jolesz. 10/2011. “Proceedings of the 4th Image Guided Therapy Workshop” 4, Pp. 1-121. 2011 IGT Workshop Proceedings
Petter Risholm, James Balter, and William M Wells III. 9/2011. “Estimation of delivered dose in radiotherapy: the influence of registration uncertainty.” Med Image Comput Comput Assist Interv, 14, Pt 1, Pp. 548-55.Abstract

We present a probabilistic framework to estimate the accumulated radiation dose and the corresponding dose uncertainty that is delivered to important anatomical structures, e.g. the primary tumor and healthy surrounding organs, during radiotherapy. The dose uncertainty we report is a direct result of uncertainties in the estimates of the deformation which aligns the daily cone-beam CT images with the planning CT. The accumulated radiation dose is an important measure to monitor during treatment, in particular to see if it significantly deviates from the planned dose which might indicate that either the patient was not properly positioned before treatment or that the anatomy has changed due to the treatment. In the case of the latter, the treatment plan should be adaptively changed to align with the current patient anatomy. We estimate the accumulated dose distribution, and its uncertainty, retrospectively on a dataset acquired during treatment of cancer in the neck and show the dose distributions in the form of dose volume histograms.

Yogesh Rathi, Oleg V Michailovich, Kawin Setsompop, Sylvain Bouix, Martha E Shenton, and Carl-Fredrik Westin. 9/2011. “Sparse Multi-shell Diffusion Imaging.” Med Image Comput Comput Assist Interv, 14, Pt 2, Pp. 58-65.Abstract

Diffusion magnetic resonance imaging (dMRI) is an important tool that allows non-invasive investigation of neural architecture of the brain. The data obtained from these in-vivo scans provides important information about the integrity and connectivity of neural fiber bundles in the brain. A multi-shell imaging (MSI) scan can be of great value in the study of several psychiatric and neurological disorders, yet its usability has been limited due to the long acquisition times required. A typical MSI scan involves acquiring a large number of gradient directions for the 2 (or more) spherical shells (several b-values), making the acquisition time significantly long for clinical application. In this work, we propose to use results from the theory of compressive sampling and determine the minimum number of gradient directions required to attain signal reconstruction similar to a traditional MSI scan. In particular, we propose a generalization of the single shell spherical ridgelets basis for sparse representation of multi shell signals. We demonstrate its efficacy on several synthetic and in-vivo data sets and perform quantitative comparisons with solid spherical harmonics based representation. Our preliminary results show that around 20-24 directions per shell are enough for robustly recovering the diffusion propagator.

Petter Risholm, James Ross, George R Washko, and William M Wells III. 7/2011. “Probabilistic Elastography: Estimating Lung Elasticity.” Inf Process Med Imaging, 22, Pp. 699-710.Abstract

We formulate registration-based elastography in a probabilistic framework and apply it to study lung elasticity in the presence of emphysematous and fibrotic tissue. The elasticity calculations are based on a Finite Element discretization of a linear elastic biomechanical model. We marginalize over the boundary conditions (deformation) of the biomechanical model to determine the posterior distribution over elasticity parameters. Image similarity is included in the likelihood, an elastic prior is included to constrain the boundary conditions, while a Markov model is used to spatially smooth the inhomogeneous elasticity. We use a Markov Chain Monte Carlo (MCMC) technique to characterize the posterior distribution over elasticity from which we extract the most probable elasticity as well as the uncertainty of this estimate. Even though registration-based lung elastography with inhomogeneous elasticity is challenging due the problem's highly underdetermined nature and the sparse image information available in lung CT, we show promising preliminary results on estimating lung elasticity contrast in the presence of emphysematous and fibrotic tissue.

Firdaus Janoos, Shantanu Singh, Raghu Machiraju, William M Wells III, and Istvan A Mórocz. 7/2011. “State-space Models of Mental Processes from fMRI.” Inf Process Med Imaging, 22, Pp. 588-99.Abstract

In addition to functional localization and integration, the problem of determining whether the data encode some information about the mental state of the subject, and if so, how this information is represented has become an important research agenda in functional neuroimaging. Multivariate classifiers, commonly used for brain state decoding, are restricted to simple experimental paradigms with a fixed number of alternatives and are limited in their representation of the temporal dimension of the task. Moreover, they learn a mapping from the data to experimental conditions and therefore do not explain the intrinsic patterns in the data. In this paper, we present a data-driven approach to building a spatio-temporal representation of mental processes using a state-space formalism, without reference to experimental conditions. Efficient Monte Carlo algorithms for estimating the parameters of the model along with a method for model-size selection are developed. The advantages of such a model in determining the mental-state of the subject over pattern classifiers are demonstrated using an fMRI study of mental arithmetic.

Lauren J O'Donnell and Carl-Fredrik Westin. 4/2011. “An Introduction to Diffusion Tensor Image Analysis.” Neurosurg Clin N Am, 22, 2, Pp. 185-96.Abstract

Diffusion tensor magnetic resonance imaging (DTI) is a relatively new technology that is popular for imaging the white matter of the brain. This article provides a basic and broad overview of DTI to enable the reader to develop an intuitive understanding of these types of data, and an awareness of their strengths and weaknesses.

Petter Risholm, Alexandra J Golby, and William M Wells III. 4/2011. “Multimodal Image Registration for Preoperative Planning and Image-guided Neurosurgical Procedures.” Neurosurg Clin N Am, 22, 2, Pp. 197-206.Abstract

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.

Ron Kikinis and Steve Pieper. 2011. “3D Slicer as a tool for interactive brain tumor segmentation.” Conf Proc IEEE Eng Med Biol Soc, 2011, Pp. 6982-4.Abstract
User interaction is required for reliable segmentation of brain tumors in clinical practice and in clinical research. By incorporating current research tools, 3D Slicer provides a set of interactive, easy to use tools that can be efficiently used for this purpose. One of the modules of 3D Slicer is an interactive editor tool, which contains a variety of interactive segmentation effects. Use of these effects for fast and reproducible segmentation of a single glioblastoma from magnetic resonance imaging data is demonstrated. The innovation in this work lies not in the algorithm, but in the accessibility of the algorithm because of its integration into a software platform that is practical for research in a clinical setting.
Il Tae Kim, Allen Tannenbaum, and Rina Tannenbaum. 2011. “Anisotropic conductivity of magnetic carbon nanotubes embedded in epoxy matrices.” Carbon N Y, 49, 1, Pp. 54-61.Abstract
Maghemite (γ-Fe(2)O(3))/multi-walled carbon nanotubes (MWCNTs) hybrid-materials were synthesized and their anisotropic electrical conductivities as a result of their alignment in a polymer matrix under an external magnetic field were investigated. The tethering of γ-Fe(2)O(3) nanoparticles on the surface of MWCNT was achieved by a modified sol-gel reaction, where sodium dodecylbenzene sulfonate (NaDDBS) was used in order to inhibit the formation of a 3D iron oxide gel. These hybrid-materials, specifically, magnetized multi-walled carbon nanotubes (m-MWCNTs) were readily aligned parallel to the direction of a magnetic field even when using a relatively weak magnetic field. The conductivity of the epoxy composites formed in this manner increased with increasing m-MWCNT mass fraction in the polymer matrix. Furthermore, the conductivities parallel to the direction of magnetic field were higher than those in the perpendicular direction, indicating that the alignment of the m-MWCNT contributed to the enhancement of the anisotropic electrical properties of the composites in the direction of alignment.
Nicola Moscufo, Charles RG Guttmann, Dominik Meier, Istvan Csapo, Peter G Hildenbrand, Brian C Healy, Julia A Schmidt, and Leslie Wolfson. 2011. “Brain regional lesion burden and impaired mobility in the elderly.” Neurobiol Aging, 32, 4, Pp. 646-54.Abstract
This study investigated the relationship of brain white matter (WM) lesions affecting specific neural networks with decreased mobility in ninety-nine healthy community-dwelling subjects ≥75 years old prospectively enrolled by age and mobility status. We assessed lesion burden in the genu, body and splenium of corpus callosum; anterior, superior and posterior corona radiata; anterior and posterior limbs of internal capsule; corticospinal tract; and superior longitudinal fasciculus. Burden in the splenium of corpus callosum (SCC) demonstrated the highest correlation particularly with walking speed (r=0.4, p<10(-4)), and in logistic regression it was the best regional predictor of low mobility performance. We also found that independent of mobility, corona radiata has the largest lesion burden with anterior (ACR) and posterior (PCR) aspects being the most frequently affected. The results suggest that compromised inter-hemispheric integration of visuospatial information through the SCC plays an important role in mobility impairment in the elderly. The relatively high lesion susceptibility of ACR and PCR in all subjects may obscure the importance of these lesions in mobility impairment.
Jacob Huang, Behnood Gholami, Nathalie YR Agar, Isaiah Norton, Wassim M Haddad, and Allen R Tannenbaum. 2011. “Classification of astrocytomas and oligodendrogliomas from mass spectrometry data using sparse kernel machines.” Conf Proc IEEE Eng Med Biol Soc, 2011, Pp. 7965-8.Abstract
Glioma histologies are the primary factor in prognostic estimates and are used in determining the proper course of treatment. Furthermore, due to the sensitivity of cranial environments, real-time tumor-cell classification and boundary detection can aid in the precision and completeness of tumor resection. A recent improvement to mass spectrometry known as desorption electrospray ionization operates in an ambient environment without the application of a preparation compound. This allows for a real-time acquisition of mass spectra during surgeries and other live operations. In this paper, we present a framework using sparse kernel machines to determine a glioma sample's histopathological subtype by analyzing its chemical composition acquired by desorption electrospray ionization mass spectrometry.
Federico Torelli, Nicola Moscufo, Girolamo Garreffa, Fabio Placidi, Andrea Romigi, Silvana Zannino, Marco Bozzali, Fabrizio Fasano, Giovanni Giulietti, Ina Djonlagic, Atul Malhotra, Maria Grazia Marciani, and Charles RG Guttmann. 2011. “Cognitive profile and brain morphological changes in obstructive sleep apnea.” Neuroimage, 54, 2, Pp. 787-93.Abstract
Obstructive sleep apnea (OSA) is accompanied by neurocognitive impairment, likely mediated by injury to various brain regions. We evaluated brain morphological changes in patients with OSA and their relationship to neuropsychological and oximetric data. Sixteen patients affected by moderate-severe OSA (age: 55.8±6.7 years, 13 males) and fourteen control subjects (age: 57.6±5.1 years, 9 males) underwent 3.0 Tesla brain magnetic resonance imaging (MRI) and neuropsychological testing evaluating short- and long-term memory, executive functions, language, attention, praxia and non-verbal learning. Volumetric segmentation of cortical and subcortical structures and voxel-based morphometry (VBM) were performed. Patients and controls differed significantly in Rey Auditory-Verbal Learning test (immediate and delayed recall), Stroop test and Digit span backward scores. Volumes of cortical gray matter (GM), right hippocampus, right and left caudate were smaller in patients compared to controls, with also brain parenchymal fraction (a normalized measure of cerebral atrophy) approaching statistical significance. Differences remained significant after controlling for comorbidities (hypertension, diabetes, smoking, hypercholesterolemia). VBM analysis showed regions of decreased GM volume in right and left hippocampus and within more lateral temporal areas in patients with OSA. Our findings indicate that the significant cognitive impairment seen in patients with moderate-severe OSA is associated with brain tissue damage in regions involved in several cognitive tasks. We conclude that OSA can increase brain susceptibility to the effects of aging and other clinical and pathological occurrences.
Behnood Gholami, Nathalie YR Agar, Ferenc A Jolesz, Wassim M Haddad, and Allen R Tannenbaum. 2011. “A compressive sensing approach for glioma margin delineation using mass spectrometry.” Conf Proc IEEE Eng Med Biol Soc, 2011, Pp. 5682-5.Abstract
Surgery, and specifically, tumor resection, is the primary treatment for most patients suffering from brain tumors. Medical imaging techniques, and in particular, magnetic resonance imaging are currently used in diagnosis as well as image-guided surgery procedures. However, studies show that computed tomography and magnetic resonance imaging fail to accurately identify the full extent of malignant brain tumors and their microscopic infiltration. Mass spectrometry is a well-known analytical technique used to identify molecules in a given sample based on their mass. In a recent study, it is proposed to use mass spectrometry as an intraoperative tool for discriminating tumor and non-tumor tissue. Integration of mass spectrometry with the resection module allows for tumor resection and immediate molecular analysis. In this paper, we propose a framework for tumor margin delineation using compressive sensing. Specifically, we show that the spatial distribution of tumor cell concentration can be efficiently reconstructed and updated using mass spectrometry information from the resected tissue. In addition, our proposed framework is model-free, and hence, requires no prior information of spatial distribution of the tumor cell concentration.
Julia H Chariker, Farah Naaz, and John R Pani. 2011. “Computer-based Learning of Neuroanatomy: A Longitudinal Study of Learning, Transfer, and Retention.” J Educ Psychol, 103, 1, Pp. 19-31.Abstract
A longitudinal experiment was conducted to evaluate the effectiveness of new methods for learning neuroanatomy with computer-based instruction. Using a 3D graphical model of the human brain, and sections derived from the model, tools for exploring neuroanatomy were developed to encourage adaptive exploration. This is an instructional method which incorporates graphical exploration in the context of repeated testing and feedback. With this approach, 72 participants learned either sectional anatomy alone or whole anatomy followed by sectional anatomy. Sectional anatomy was explored either with perceptually continuous navigation through the sections or with discrete navigation (as in the use of an anatomical atlas). Learning was measured longitudinally to a high performance criterion. Subsequent tests examined transfer of learning to the interpretation of biomedical images and long-term retention. There were several clear results of this study. On initial exposure to neuroanatomy, whole anatomy was learned more efficiently than sectional anatomy. After whole anatomy was mastered, learners demonstrated high levels of transfer of learning to sectional anatomy and from sectional anatomy to the interpretation of complex biomedical images. Learning whole anatomy prior to learning sectional anatomy led to substantially fewer errors overall than learning sectional anatomy alone. Use of continuous or discrete navigation through sectional anatomy made little difference to measured outcomes. Efficient learning, good long-term retention, and successful transfer to the interpretation of biomedical images indicated that computer-based learning using adaptive exploration can be a valuable tool in instruction of neuroanatomy and similar disciplines.
Georg Langs, Bjoern H Menze, Danial Lashkari, and Polina Golland. 2011. “Detecting stable distributed patterns of brain activation using Gini contrast.” Neuroimage, 56, 2, Pp. 497-507.Abstract
The relationship between spatially distributed fMRI patterns and experimental stimuli or tasks offers insights into cognitive processes beyond those traceable from individual local activations. The multivariate properties of the fMRI signals allow us to infer interactions among individual regions and to detect distributed activations of multiple areas. Detection of task-specific multivariate activity in fMRI data is an important open problem that has drawn much interest recently. In this paper, we study and demonstrate the benefits of random forest classifiers and the associated Gini importance measure for selecting voxel subsets that form a multivariate neural response. The Gini importance measure quantifies the predictive power of a particular feature when considered as part of the entire pattern. The measure is based on a random sampling of fMRI time points and voxels. As a consequence the resulting voxel score, or Gini contrast, is highly reproducible and reliably includes all informative features. The method does not rely on a priori assumptions about the signal distribution, a specific statistical or functional model or regularization. Instead, it uses the predictive power of features to characterize their relevance for encoding task information. The Gini contrast offers an additional advantage of directly quantifying the task-relevant information in a multiclass setting, rather than reducing the problem to several binary classification subproblems. In a multicategory visual fMRI study, the proposed method identified informative regions not detected by the univariate criteria, such as the t-test or the F-test. Including these additional regions in the feature set improves the accuracy of multicategory classification. Moreover, we demonstrate higher classification accuracy and stability of the detected spatial patterns across runs than the traditional methods such as the recursive feature elimination used in conjunction with support vector machines.
Nathalie YR Agar, Alexandra J Golby, Keith L Ligon, Isaiah Norton, Vandana Mohan, Justin M Wiseman, Allen Tannenbaum, and Ferenc A Jolesz. 2011. “Development of stereotactic mass spectrometry for brain tumor surgery.” Neurosurgery, 68, 2, Pp. 280-89; discussion 290.Abstract
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.
Andrew Zalesky, Alex Fornito, Marc L Seal, Luca Cocchi, Carl-Fredrik Westin, Edward T Bullmore, Gary F Egan, and Christos Pantelis. 2011. “Disrupted axonal fiber connectivity in schizophrenia.” Biol Psychiatry, 69, 1, Pp. 80-9.Abstract
BACKGROUND: Schizophrenia is believed to result from abnormal functional integration of neural processes thought to arise from aberrant brain connectivity. However, evidence for anatomical dysconnectivity has been equivocal, and few studies have examined axonal fiber connectivity in schizophrenia at the level of whole-brain networks. METHODS: Cortico-cortical anatomical connectivity at the scale of axonal fiber bundles was modeled as a network. Eighty-two network nodes demarcated functionally specific cortical regions. Sixty-four direction diffusion tensor-imaging coupled with whole-brain tractography was performed to map the architecture via which network nodes were interconnected in each of 74 patients with schizophrenia and 32 age- and gender-matched control subjects. Testing was performed to identify pairs of nodes between which connectivity was impaired in the patient group. The connectional architecture of patients was tested for changes in five network attributes: nodal degree, small-worldness, efficiency, path length, and clustering. RESULTS: Impaired connectivity in the patient group was found to involve a distributed network of nodes comprising medial frontal, parietal/occipital, and the left temporal lobe. Although small-world attributes were conserved in schizophrenia, the cortex was interconnected more sparsely and up to 20% less efficiently in patients. Intellectual performance was found to be associated with brain efficiency in control subjects but not in patients. CONCLUSIONS: This study presents evidence of widespread dysconnectivity in white-matter connectional architecture in a large sample of patients with schizophrenia. When considered from the perspective of recent evidence for impaired synaptic plasticity, this study points to a multifaceted pathophysiology in schizophrenia encompassing axonal as well as putative synaptic mechanisms.
Padmavathi Sundaram, Robert V Mulkern, William M Wells, Christina Triantafyllou, Tobias Loddenkemper, Ellen J Bubrick, and Darren B Orbach. 2011. “An empirical investigation of motion effects in eMRI of interictal epileptiform spikes.” Magn Reson Imaging, 29, 10, Pp. 1401-9.Abstract
We recently developed a functional neuroimaging technique called encephalographic magnetic resonance imaging (eMRI). Our method acquires rapid single-shot gradient-echo echo-planar MRI (repetition time=47 ms); it attempts to measure an MR signal more directly linked to neuronal electromagnetic activity than existing methods. To increase the likelihood of detecting such an MR signal, we recorded concurrent MRI and scalp electroencephalography (EEG) during fast (20-200 ms), localized, high-amplitude (>50 μV on EEG) cortical discharges in a cohort of focal epilepsy patients. Seen on EEG as interictal spikes, these discharges occur in between seizures and induced easily detectable MR magnitude and phase changes concurrent with the spikes with a lag of milliseconds to tens of milliseconds. Due to the time scale of the responses, localized changes in blood flow or hemoglobin oxygenation are unlikely to cause the MR signal changes that we observed. While the precise underlying mechanisms are unclear, in this study, we empirically investigate one potentially important confounding variable - motion. Head motion in the scanner affects both EEG and MR recording. It can produce brief "spike-like" artifacts on EEG and induce large MR signal changes similar to our interictal spike-related signal changes. In order to explore the possibility that interictal spikes were associated with head motions (although such an association had never been reported), we had previously tracked head position in epilepsy patients during interictal spikes and explicitly demonstrated a lack of associated head motion. However, that study was performed outside the MR scanner, and the root-mean-square error in the head position measurement was 0.7 mm. The large inaccuracy in this measurement therefore did not definitively rule out motion as a possible signal generator. In this study, we instructed healthy subjects to make deliberate brief (<500 ms) head motions inside the MR scanner and imaged these head motions with concurrent EEG and MRI. We compared these artifactual MR and EEG data to genuine interictal spikes. While per-voxel MR and per-electrode EEG time courses for the motion case can mimic the corresponding time courses associated with a genuine interictal spike, head motion can be unambiguously differentiated from interictal spikes via scalp EEG potential maps. Motion induces widespread changes in scalp potential, whereas interictal spikes are localized and have a regional fall-off in amplitude. These findings make bulk head motion an unlikely generator of the large spike-related MR signal changes that we had observed. Further work is required to precisely identify the underlying mechanisms.
Liangjia Zhu, Yi Gao, Vandana Mohan, Arthur Stillman, Tracy Faber, and Allen Tannenbaum. 2011. “Estimation of Myocardial Volume at Risk from CT Angiography.” Proc SPIE Int Soc Opt Eng, 7963, Pp. 79632A-79632A6.Abstract
The determination of myocardial volume at risk distal to coronary stenosis provides important information for prognosis and treatment of coronary artery disease. In this paper, we present a novel computational framework for estimating the myocardial volume at risk in computed tomography angiography (CTA) imagery. Initially, epicardial and endocardial surfaces, and coronary arteries are extracted using an active contour method. Then, the extracted coronary arteries are projected onto the epicardial surface, and each point on this surface is associated with its closest coronary artery using the geodesic distance measurement. The likely myocardial region at risk on the epicardial surface caused by a stenosis is approximated by the region in which all its inner points are associated with the sub-branches distal to the stenosis on the coronary artery tree. Finally, the likely myocardial volume at risk is approximated by the volume in between the region at risk on the epicardial surface and its projection on the endocardial surface, which is expected to yield computational savings over risk volume estimation using the entire image volume. Furthermore, we expect increased accuracy since, as compared to prior work using the Euclidean distance, we employ the geodesic distance in this work. The experimental results demonstrate the effectiveness of the proposed approach on pig heart CTA datasets.
Stefan Lienhard, James G Malcolm, Carl-Frederik Westin, and Yogesh Rathi. 2011. “A full bi-tensor neural tractography algorithm using the unscented Kalman filter.” EURASIP J Adv Signal Process, 2011.Abstract
We describe a technique that uses tractography to visualize neural pathways in human brains by extending an existing framework that uses overlapping Gaussian tensors to model the signal. At each point on the fiber, an unscented Kalman filter is used to find the most consistent direction as a mixture of previous estimates and of the local model. In our previous framework, the diffusion ellipsoid had a cylindrical shape, i.e., the diffusion tensor's second and third eigenvalues were identical. In this paper, we extend the tensor representation so that the diffusion tensor is represented by an arbitrary ellipsoid. Experiments on synthetic data show a reduction in the angular error at fiber crossings and branchings. Tests on in vivo data demonstrate the ability to trace fibers in areas containing crossings or branchings, and the tests also confirm the superiority of using a full tensor representation over the simplified model.