Publications

2017
Yangming Ou, Lilla Zöllei, Kallirroi Retzepi, Victor Castro, Sara V Bates, Steve Pieper, Katherine P Andriole, Shawn N Murphy, Randy L Gollub, and Patricia Ellen Grant. 6/2017. “Using Clinically Acquired MRI to Construct Age-specific Atlases: Quantifying Spatiotemporal ADC Changes from Birth to 6-year Old.” Hum Brain Mapp, 38, 6, Pp. 3052-3068.Abstract
Diffusion imaging is critical for detecting acute brain injury. However, normal apparent diffusion coefficient (ADC) maps change rapidly in early childhood, making abnormality detection difficult. In this article, we explored clinical PACS and electronic healthcare records (EHR) to create age-specific ADC atlases for clinical radiology reference. Using the EHR and three rounds of multiexpert reviews, we found ADC maps from 201 children 0-6 years of age scanned between 2006 and 2013 who had brain MRIs with no reported abnormalities and normal clinical evaluations 2+ years later. These images were grouped in 10 age bins, densely sampling the first 1 year of life (5 bins, including neonates and 4 quarters) and representing the 1-6 year age range (an age bin per year). Unbiased group-wise registration was used to construct ADC atlases for 10 age bins. We used the atlases to quantify (a) cross-sectional normative ADC variations; (b) spatiotemporal heterogeneous ADC changes; and (c) spatiotemporal heterogeneous volumetric changes. The quantified age-specific whole-brain and region-wise ADC values were compared to those from age-matched individual subjects in our study and in multiple existing independent studies. The significance of this study is that we have shown that clinically acquired images can be used to construct normative age-specific atlases. These first of their kind age-specific normative ADC atlases quantitatively characterize changes of myelination-related water diffusion in the first 6 years of life. The quantified voxel-wise spatiotemporal ADC variations provide standard references to assist radiologists toward more objective interpretation of abnormalities in clinical images. Our atlases are available at https://www.nitrc.org/projects/mgh_adcatlases.
Walid I Essayed, Fan Zhang, Prashin Unadkat, Rees G Cosgrove, Alexandra J Golby, and Lauren J O'Donnell. 6/2017. “White Matter Tractography for Neurosurgical Planning: A Topography-based Review of the Current State of the Art.” Neuroimage Clin, 15, Pp. 659-72.Abstract
We perform a review of the literature in the field of white matter tractography for neurosurgical planning, focusing on those works where tractography was correlated with clinical information such as patient outcome, clinical functional testing, or electro-cortical stimulation. We organize the review by anatomical location in the brain and by surgical procedure, including both supratentorial and infratentorial pathologies, and excluding spinal cord applications. Where possible, we discuss implications of tractography for clinical care, as well as clinically relevant technical considerations regarding the tractography methods. We find that tractography is a valuable tool in variable situations in modern neurosurgery. Our survey of recent reports demonstrates multiple potentially successful applications of white matter tractography in neurosurgery, with progress towards overcoming clinical challenges of standardization and interpretation.
Karl-Heinz Nenning, Hesheng Liu, Satrajit S Ghosh, Mert R Sabuncu, Ernst Schwartz, and Georg Langs. 4/2017. “Diffeomorphic Functional Brain Surface Alignment: Functional Demons.” Neuroimage.Abstract
Aligning brain structures across individuals is a central prerequisite for comparative neuroimaging studies. Typically, registration approaches assume a strong association between the features used for alignment, such as macro-anatomy, and the variable observed, such as functional activation or connectivity. Here, we propose to use the structure of intrinsic resting state fMRI signal correlation patterns as a basis for alignment of the cortex in functional studies. Rather than assuming the spatial correspondence of functional structures between subjects, we have identified locations with similar connectivity profiles across subjects. We mapped functional connectivity relationships within the brain into an embedding space, and aligned the resulting maps of multiple subjects. We then performed a diffeomorphic alignment of the cortical surfaces, driven by the corresponding features in the joint embedding space. Results show that functional alignment based on resting state fMRI identifies functionally homologous regions across individuals with higher accuracy than alignment based on the spatial correspondence of anatomy. Further, functional alignment enables measurement of the strength of the anatomo-functional link across the cortex, and reveals the uneven distribution of this link. Stronger anatomo-functional dissociation was found in higher association areas compared to primary sensory- and motor areas. Functional alignment based on resting state features improves group analysis of task based functional MRI data, increasing statistical power and improving the delineation of task-specific core regions. Finally, a comparison of the anatomo-functional dissociation between cohorts is demonstrated with a group of left and right handed subjects.
Inbar Seroussi, Denis S Grebenkov, Ofer Pasternak, and Nir Sochen. 4/2017. “Microscopic Interpretation and Generalization of the Bloch-Torrey Equation for Diffusion Magnetic Resonance.” J Magn Reson, 277, Pp. 95-103.Abstract
In order to bridge microscopic molecular motion with macroscopic diffusion MR signal in complex structures, we propose a general stochastic model for molecular motion in a magnetic field. The Fokker-Planck equation of this model governs the probability density function describing the diffusion-magnetization propagator. From the propagator we derive a generalized version of the Bloch-Torrey equation and the relation to the random phase approach. This derivation does not require assumptions such as a spatially constant diffusion coefficient, or ad hoc selection of a propagator. In particular, the boundary conditions that implicitly incorporate the microstructure into the diffusion MR signal can now be included explicitly through a spatially varying diffusion coefficient. While our generalization is reduced to the conventional Bloch-Torrey equation for piecewise constant diffusion coefficients, it also predicts scenarios in which an additional term to the equation is required to fully describe the MR signal.
Chantal MW Tax, Carl-Fredrik Westin, Tom Dela Haije, Andrea Fuster, Max A Viergever, Evan Calabrese, Luc Florack, and Alexander Leemans. 4/2017. “Quantifying the Brain's Sheet Structure with Normalized Convolution.” Med Image Anal, 39, Pp. 162-77.Abstract
The hypothesis that brain pathways form 2D sheet-like structures layered in 3D as "pages of a book" has been a topic of debate in the recent literature. This hypothesis was mainly supported by a qualitative evaluation of "path neighborhoods" reconstructed with diffusion MRI (dMRI) tractography. Notwithstanding the potentially important implications of the sheet structure hypothesis for our understanding of brain structure and development, it is still considered controversial by many for lack of quantitative analysis. A means to quantify sheet structure is therefore necessary to reliably investigate its occurrence in the brain. Previous work has proposed the Lie bracket as a quantitative indicator of sheet structure, which could be computed by reconstructing path neighborhoods from the peak orientations of dMRI orientation density functions. Robust estimation of the Lie bracket, however, is challenging due to high noise levels and missing peak orientations. We propose a novel method to estimate the Lie bracket that does not involve the reconstruction of path neighborhoods with tractography. This method requires the computation of derivatives of the fiber peak orientations, for which we adopt an approach called normalized convolution. With simulations and experimental data we show that the new approach is more robust with respect to missing peaks and noise. We also demonstrate that the method is able to quantify to what extent sheet structure is supported for dMRI data of different species, acquired with different scanners, diffusion weightings, dMRI sampling schemes, and spatial resolutions. The proposed method can also be used with directional data derived from other techniques than dMRI, which will facilitate further validation of the existence of sheet structure.
Anna S Rydhög, Filip Szczepankiewicz, Ronnie Wirestam, André Ahlgren, Carl-Fredrik Westin, Linda Knutsson, and Ofer Pasternak. 4/2017. “Separating Blood and Water: Perfusion and Free Water Elimination from Diffusion MRI in the Human Brain.” Neuroimage.Abstract
The assessment of the free water fraction in the brain provides important information about extracellular processes such as atrophy and neuroinflammation in various clinical conditions as well as in normal development and aging. Free water estimates from diffusion MRI are assumed to account for freely diffusing water molecules in the extracellular space, but may be biased by other pools of molecules in rapid random motion, such as the intravoxel incoherent motion (IVIM) of blood, where water molecules perfuse in the randomly oriented capillary network. The goal of this work was to separate the signal contribution of the perfusing blood from that of free-water and of other brain diffusivities. The influence of the vascular compartment on the estimation of the free water fraction and other diffusivities was investigated by simulating perfusion in diffusion MRI data. The perfusion effect in the simulations was significant, especially for the estimation of the free water fraction, and was maintained as long as low b-value data were included in the analysis. Two approaches to reduce the perfusion effect were explored in this study: (i) increasing the minimal b-value used in the fitting, and (ii) using a three-compartment model that explicitly accounts for water molecules in the capillary blood. Estimation of the model parameters while excluding low b-values reduced the perfusion effect but was highly sensitive to noise. The three-compartment model fit was more stable and additionally, provided an estimation of the volume fraction of the capillary blood compartment. The three-compartment model thus disentangles the effects of free water diffusion and perfusion, which is of major clinical importance since changes in these components in the brain may indicate different pathologies, i.e., those originating from the extracellular space, such as neuroinflammation and atrophy, and those related to the vascular space, such as vasodilation, vasoconstriction and capillary density. Diffusion MRI data acquired from a healthy volunteer, using multiple b-shells, demonstrated an expected non-zero contribution from the blood fraction, and indicated that not accounting for the perfusion effect may explain the overestimation of the free water fraction evinced in previous studies. Finally, the applicability of the method was demonstrated with a dataset acquired using a clinically feasible protocol with shorter acquisition time and fewer b-shells.
Amanda E Lyall, Ofer Pasternak, DG Robinson, D Newell, JW Trampush, JA Gallego, M Fava, AK Malhotra, KH Karlsgodt, Marek Kubicki, and PR Szeszko. 3/28/2017. “Greater Extracellular Free-Water in First-Episode Psychosis Predicts Better Neurocognitive Functioning.” Mol Psychiatry.Abstract

Free Water Imaging is a novel diffusion magnetic resonance (MR) imaging method that is able to separate changes affecting the extracellular space from those that reflect changes in neuronal cells and processes. A previous Free Water Imaging study in schizophrenia identified significantly greater extracellular water volume in the early stages of the disorder; however, its clinical and functional sequelae have not yet been investigated. Here, we applied Free Water Imaging to a larger cohort of 63 first-episode patients with psychosis and 70 healthy matched controls to better understand the functional significance of greater extracellular water. We used diffusion MR imaging data and the Tract-Based Spatial Statistics analytic pipeline to first analyze fractional anisotropy (FA), the most commonly employed metric for assessing white matter. This comparison was then followed by Free Water Imaging analysis, where two parameters, the fractional volume of extracellular free-water (FW) and cellular tissue FA (FA-t), were estimated and compared across the entire white matter skeleton between groups, and correlated with cognitive measures at baseline and following 12 weeks of antipsychotic treatment. Our results indicated lower FA across the whole brain in patients compared with healthy controls that overlap with significant increases in FW, with only limited decreases in FA-t. In addition, higher FW correlated with better neurocognitive functioning following 12 weeks of antipsychotic treatment. We believe this is the first study to suggest that an extracellular water increase during the first-episode of psychosis, which may be indicative of an acute neuroinflammatory process, and/or cerebral edema may predict better functional outcome.

Xiaojun Chen, Lu Xu, Huixiang Wang, Fang Wang, Qiugen Wang, and Ron Kikinis. 3/2017. “Development of a Surgical Navigation System Based on 3D Slicer for Intraoperative Implant Placement Surgery.” Med Eng Phys, 41, Pp. 81-9.Abstract

Implant placement has been widely used in various kinds of surgery. However, accurate intraoperative drilling performance is essential to avoid injury to adjacent structures. Although some commercially-available surgical navigation systems have been approved for clinical applications, these systems are expensive and the source code is not available to researchers. 3D Slicer is a free, open source software platform for the research community of computer-aided surgery. In this study, a loadable module based on Slicer has been developed and validated to support surgical navigation. This research module allows reliable calibration of the surgical drill, point-based registration and surface matching registration, so that the position and orientation of the surgical drill can be tracked and displayed on the computer screen in real time, aiming at reducing risks. In accuracy verification experiments, the mean target registration error (TRE) for point-based and surface-based registration were 0.31±0.06mm and 1.01±0.06mm respectively, which should meet clinical requirements. Both phantom and cadaver experiments demonstrated the feasibility of our surgical navigation software module.

Magnus Herberthson, Evren Özarslan, Hans Knutsson, and Carl-Fredrik Westin. 3/2017. “Dynamics of Local Magnetization in the Eigenbasis of the Bloch-Torrey Operator.” J Chem Phys, 146, 12, Pp. 124201.Abstract

We consider diffusion within pores with general shapes in the presence of spatially linear magnetic field profiles. The evolution of local magnetization of the spin bearing particles can be described by the Bloch-Torrey equation. We study the diffusive process in the eigenbasis of the non-Hermitian Bloch-Torrey operator. It is possible to find expressions for some special temporal gradient waveforms employed to sensitize the nuclear magnetic resonance (NMR) signal to diffusion. For more general gradient waveforms, we derive an efficient numerical solution by introducing a novel matrix formalism. Compared to previous methods, this new approach requires a fewer number of eigenfunctions to achieve the same accuracy. This shows that these basis functions are better suited to the problem studied. The new framework could provide new important insights into the fundamentals of diffusion sensitization, which could further the development of the field of NMR.

Sonia Pujol, Ryan Cabeen, Sophie B Sébille, Jérôme Yelnik, Chantal François, Sara Fernandez Vidal, Carine Karachi, Yulong Zhao, Rees G Cosgrove, Pierre Jannin, Ron Kikinis, and Eric Bardinet. 3/2017. “In vivo Exploration of the Connectivity between the Subthalamic Nucleus and the Globus Pallidus in the Human Brain using Multi-Fiber Tractography.” Front Neuroanat, 10, Pp. 119.Abstract

The basal ganglia is part of a complex system of neuronal circuits that play a key role in the integration and execution of motor, cognitive and emotional function in the human brain. Parkinson's disease is a progressive neurological disorder of the motor circuit characterized by tremor, rigidity, and slowness of movement. Deep brain stimulation (DBS) of the subthalamic nucleus and the globus pallidus pars interna provides an efficient treatment to reduce symptoms and levodopa-induced side effects in Parkinson's disease patients. While the underlying mechanism of action of DBS is still unknown, the potential modulation of white matter tracts connecting the surgical targets has become an active area of research. With the introduction of advanced diffusion MRI acquisition sequences and sophisticated post-processing techniques, the architecture of the human brain white matter can be explored in vivo. The goal of this study is to investigate the white matter connectivity between the subthalamic nucleus and the globus pallidus. Two multi-fiber tractography methods were used to reconstruct pallido-subthalamic, subthalamo-pallidal and pyramidal fibers in five healthy subjects datasets of the Human Connectome Project. The anatomical accuracy of the tracts was assessed by four judges with expertise in neuroanatomy, functional neurosurgery, and diffusion MRI. The variability among subjects was evaluated based on the fractional anisotropy and mean diffusivity of the tracts. Both multi-fiber approaches enabled the detection of complex fiber architecture in the basal ganglia. The qualitative evaluation by experts showed that the identified tracts were in agreement with the expected anatomy. Tract-derived measurements demonstrated relatively low variability among subjects. False-negative tracts demonstrated the current limitations of both methods for clinical decision-making. Multi-fiber tractography methods combined with state-of-the-art diffusion MRI data have the potential to help identify white matter tracts connecting DBS targets in functional neurosurgery intervention.

Joseph J Shaffer, Ali Ghayoor, Jeffrey D Long, Regina Eun-Young Kim, Spencer Lourens, Lauren J O'Donnell, Carl-Fredrik Westin, Yogesh Rathi, Vincent Magnotta, Jane S Paulsen, and Hans J Johnson. 3/2017. “Longitudinal Diffusion Changes in Prodromal and Early HD: Evidence of White-matter Tract Deterioration.” Hum Brain Mapp, 38, 3, Pp. 1460-77.Abstract

INTRODUCTION: Huntington's disease (HD) is a genetic neurodegenerative disorder that primarily affects striatal neurons. Striatal volume loss is present years before clinical diagnosis; however, white matter degradation may also occur prior to diagnosis. Diffusion-weighted imaging (DWI) can measure microstructural changes associated with degeneration that precede macrostructural changes. DWI derived measures enhance understanding of degeneration in prodromal HD (pre-HD). METHODS: As part of the PREDICT-HD study, N = 191 pre-HD individuals and 70 healthy controls underwent two or more (baseline and 1-5 year follow-up) DWI, with n = 649 total sessions. Images were processed using cutting-edge DWI analysis methods for large multicenter studies. Diffusion tensor imaging (DTI) metrics were computed in selected tracts connecting the primary motor, primary somato-sensory, and premotor areas of the cortex with the subcortical caudate and putamen. Pre-HD participants were divided into three CAG-Age Product (CAP) score groups reflecting clinical diagnosis probability (low, medium, or high probabilities). Baseline and longitudinal group differences were examined using linear mixed models. RESULTS: Cross-sectional and longitudinal differences in DTI measures were present in all three CAP groups compared with controls. The high CAP group was most affected. CONCLUSIONS: This is the largest longitudinal DWI study of pre-HD to date. Findings showed DTI differences, consistent with white matter degeneration, were present up to a decade before predicted HD diagnosis. Our findings indicate a unique role for disrupted connectivity between the premotor area and the putamen, which may be closely tied to the onset of motor symptoms in HD. 

Michael Halle, Valentin Demeusy, and Ron Kikinis. 3/2017. “The Open Anatomy Browser: A Collaborative Web-Based Viewer for Interoperable Anatomy Atlases.” Front Neuroinform, 11, Pp. 22.Abstract

The Open Anatomy Browser (OABrowser) is an open source, web-based, zero-installation anatomy atlas viewer based on current web browser technologies and evolving anatomy atlas interoperability standards. OABrowser displays three-dimensional anatomical models, image cross-sections of labeled structures and source radiological imaging, and a text-based hierarchy of structures. The viewer includes novel collaborative tools: users can save bookmarks of atlas views for later access and exchange those bookmarks with other users, and dynamic shared views allow groups of users can participate in a collaborative interactive atlas viewing session. We have published several anatomy atlases (an MRI-derived brain atlas and atlases of other parts of the anatomy) to demonstrate OABrowser's functionality. The atlas source data, processing tools, and the source for OABrowser are freely available through GitHub and are distributed under a liberal open source license.

David Black, Julian Hettig, Maria Luz, Christian Hansen, Ron Kikinis, and Horst Hahn. 2/17/2017. “Auditory Feedback to Support Image-Guided Medical Needle Placement.” Int J Comput Assist Radiol Surg.Abstract

PURPOSE: During medical needle placement using image-guided navigation systems, the clinician must concentrate on a screen. To reduce the clinician's visual reliance on the screen, this work proposes an auditory feedback method as a stand-alone method or to support visual feedback for placing the navigated medical instrument, in this case a needle. METHODS: An auditory synthesis model using pitch comparison and stereo panning parameter mapping was developed to augment or replace visual feedback for navigated needle placement. In contrast to existing approaches which augment but still require a visual display, this method allows view-free needle placement. An evaluation with 12 novice participants compared both auditory and combined audiovisual feedback against existing visual methods. RESULTS: Using combined audiovisual display, participants show similar task completion times and report similar subjective workload and accuracy while viewing the screen less compared to using the conventional visual method. The auditory feedback leads to higher task completion times and subjective workload compared to both combined and visual feedback. CONCLUSION: Audiovisual feedback shows promising results and establishes a basis for applying auditory feedback as a supplement to visual information to other navigated interventions, especially those for which viewing a patient is beneficial or necessary.

Lipeng Ning, Evren Özarslan, Carl-Fredrik Westin, and Yogesh Rathi. 2/1/2017. “Precise Inference and Characterization of Structural Organization (PICASO) of Tissue from Molecular Diffusion.” Neuroimage, 146, Pp. 452-73.Abstract

Inferring the microstructure of complex media from the diffusive motion of molecules is a challenging problem in diffusion physics. In this paper, we introduce a novel representation of diffusion MRI (dMRI) signal from tissue with spatially-varying diffusivity using a diffusion disturbance function. This disturbance function contains information about the (intra-voxel) spatial fluctuations in diffusivity due to restrictions, hindrances and tissue heterogeneity of the underlying tissue substrate. We derive the short- and long-range disturbance coefficients from this disturbance function to characterize the tissue structure and organization. Moreover, we provide an exact relation between the disturbance coefficients and the time-varying moments of the diffusion propagator, as well as their relation to specific tissue microstructural information such as the intra-axonal volume fraction and the apparent axon radius. The proposed approach is quite general and can model dMRI signal for any type of gradient sequence (rectangular, oscillating, etc.) without using the Gaussian phase approximation. The relevance of the proposed PICASO model is explored using Monte-Carlo simulations and in-vivo dMRI data. The results show that the estimated disturbance coefficients can distinguish different types of microstructural organization of axons.

Guillermo Gallardo, William M Wells III, Rachid Deriche, and Demian Wassermann. 2/2017. “Groupwise Structural Parcellation of the Whole Cortex: A Logistic Random Effects Model Based Approach.” Neuroimage.Abstract

Current theories hold that brain function is highly related to long-range physical connections through axonal bundles, namely extrinsic connectivity. However, obtaining a groupwise cortical parcellation based on extrinsic connectivity remains challenging. Current parcellation methods are computationally expensive; need tuning of several parameters or rely on ad-hoc constraints. Furthermore, none of these methods present a model for the cortical extrinsic connectivity of the cortex. To tackle these problems, we propose a parsimonious model for the extrinsic connectivity and an efficient parceling technique based on clustering of tractograms. Our technique allows the creation of single subject and groupwise parcellations of the whole cortex. The parcellations obtained with our technique are in agreement with structural and functional parcellations in the literature. In particular, the motor and sensory cortex are subdivided in agreement with the human homunculus of Penfield. We illustrate this by comparing our resulting parcels with the motor strip mapping included in the Human Connectome Project data.

Rahul Sastry, Wenya Linda Bi, Steve Pieper, Sarah Frisken, Tina Kapur, William M Wells III, and Alexandra J Golby. 1/2017. “Applications of Ultrasound in the Resection of Brain Tumors.” J Neuroimaging, 27, 1, Pp. 5-15.Abstract

Neurosurgery makes use of preoperative imaging to visualize pathology, inform surgical planning, and evaluate the safety of selected approaches. The utility of preoperative imaging for neuronavigation, however, is diminished by the well-characterized phenomenon of brain shift, in which the brain deforms intraoperatively as a result of craniotomy, swelling, gravity, tumor resection, cerebrospinal fluid (CSF) drainage, and many other factors. As such, there is a need for updated intraoperative information that accurately reflects intraoperative conditions. Since 1982, intraoperative ultrasound has allowed neurosurgeons to craft and update operative plans without ionizing radiation exposure or major workflow interruption. Continued evolution of ultrasound technology since its introduction has resulted in superior imaging quality, smaller probes, and more seamless integration with neuronavigation systems. Furthermore, the introduction of related imaging modalities, such as 3-dimensional ultrasound, contrast-enhanced ultrasound, high-frequency ultrasound, and ultrasound elastography, has dramatically expanded the options available to the neurosurgeon intraoperatively. In the context of these advances, we review the current state, potential, and challenges of intraoperative ultrasound for brain tumor resection. We begin by evaluating these ultrasound technologies and their relative advantages and disadvantages. We then review three specific applications of these ultrasound technologies to brain tumor resection: (1) intraoperative navigation, (2) assessment of extent of resection, and (3) brain shift monitoring and compensation. We conclude by identifying opportunities for future directions in the development of ultrasound technologies.

Angela Albi, Ofer Pasternak, Ludovico Minati, Moira Marizzoni, David Bartrés-Faz, Núria Bargalló, Beatriz Bosch, Paolo Maria Rossini, Camillo Marra, Bernhard Müller, Ute Fiedler, Jens Wiltfang, Luca Roccatagliata, Agnese Picco, Flavio Mariano Nobili, Oliver Blin, Julien Sein, Jean-Philippe Ranjeva, Mira Didic, Stephanie Bombois, Renaud Lopes, Régis Bordet, Hélène Gros-Dagnac, Pierre Payoux, Giada Zoccatelli, Franco Alessandrini, Alberto Beltramello, Antonio Ferretti, Massimo Caulo, Marco Aiello, Carlo Cavaliere, Andrea Soricelli, Lucilla Parnetti, Roberto Tarducci, Piero Floridi, Magda Tsolaki, Manos Constantinidis, Antonios Drevelegas, Giovanni Frisoni, Jorge Jovicich, and Jorge Jovicich. 1/2017. “Free Water Elimination Improves Test-Retest Reproducibility of Diffusion Tensor Imaging Indices in the Brain: A Longitudinal Multisite Study of Healthy Elderly Subjects.” Hum Brain Mapp, 38, 1, Pp. 12-26.Abstract

Free water elimination (FWE) in brain diffusion MRI has been shown to improve tissue specificity in human white matter characterization both in health and in disease. Relative to the classical diffusion tensor imaging (DTI) model, FWE is also expected to increase sensitivity to microstructural changes in longitudinal studies. However, it is not clear if these two models differ in their test-retest reproducibility. This study compares a bi-tensor model for FWE with DTI by extending a previous longitudinal-reproducibility 3T multisite study (10 sites, 7 different scanner models) of 50 healthy elderly participants (55-80 years old) scanned in two sessions at least 1 week apart. We computed the reproducibility of commonly used DTI metrics (FA: fractional anisotropy, MD: mean diffusivity, RD: radial diffusivity, and AXD: axial diffusivity), derived either using a DTI model or a FWE model. The DTI metrics were evaluated over 48 white-matter regions of the JHU-ICBM-DTI-81 white-matter labels atlas, and reproducibility errors were assessed. We found that relative to the DTI model, FWE significantly reduced reproducibility errors in most areas tested. In particular, for the FA and MD metrics, there was an average reduction of approximately 1% in the reproducibility error. The reproducibility scores did not significantly differ across sites. This study shows that FWE improves sensitivity and is thus promising for clinical applications, with the potential to identify more subtle changes. The increased reproducibility allows for smaller sample size or shorter trials in studies evaluating biomarkers of disease progression or treatment effects. Hum Brain Mapp 38:12-26, 2017. © 2016 Wiley Periodicals, Inc.

Jorge L Bernal-Rusiel, Nicolas Rannou, Randy L Gollub, Steve Pieper, Shawn Murphy, Richard Robertson, Patricia E Grant, and Rudolph Pienaar. 2017. “Reusable Client-Side JavaScript Modules for Immersive Web-Based Real-Time Collaborative Neuroimage Visualization.” Front Neuroinform, 11, Pp. 32.Abstract
In this paper we present a web-based software solution to the problem of implementing real-time collaborative neuroimage visualization. In both clinical and research settings, simple and powerful access to imaging technologies across multiple devices is becoming increasingly useful. Prior technical solutions have used a server-side rendering and push-to-client model wherein only the server has the full image dataset. We propose a rich client solution in which each client has all the data and uses the Google Drive Realtime API for state synchronization. We have developed a small set of reusable client-side object-oriented JavaScript modules that make use of the XTK toolkit, a popular open-source JavaScript library also developed by our team, for the in-browser rendering and visualization of brain image volumes. Efficient realtime communication among the remote instances is achieved by using just a small JSON object, comprising a representation of the XTK image renderers' state, as the Google Drive Realtime collaborative data model. The developed open-source JavaScript modules have already been instantiated in a web-app called MedView, a distributed collaborative neuroimage visualization application that is delivered to the users over the web without requiring the installation of any extra software or browser plugin. This responsive application allows multiple physically distant physicians or researchers to cooperate in real time to reach a diagnosis or scientific conclusion. It also serves as a proof of concept for the capabilities of the presented technological solution.
Mukund Balasubramanian, William M Wells, John R Ives, Patrick Britz, Robert V Mulkern, and Darren B Orbach. 2017. “RF Heating of Gold Cup and Conductive Plastic Electrodes during Simultaneous EEG and MRI.” Neurodiagn J, 57, 1, Pp. 69-83.Abstract
PURPOSE: To investigate the heating of EEG electrodes during magnetic resonance imaging (MRI) scans and to better understand the underlying physical mechanisms with a focus on the antenna effect. MATERIALS AND METHODS: Gold cup and conductive plastic electrodes were placed on small watermelons with fiberoptic probes used to measure electrode temperature changes during a variety of 1.5T and 3T MRI scans. A subset of these experiments was repeated on a healthy human volunteer. RESULTS: The differences between gold and plastic electrodes did not appear to be practically significant. For both electrode types, we observed heating below 4°C for straight wires whose lengths were multiples of ½ the radiofrequency (RF) wavelength and stronger heating (over 15°C) for wire lengths that were odd multiples of ¼ RF wavelength, consistent with the antenna effect. CONCLUSIONS: The antenna effect, which has received little attention so far in the context of EEG-MRI safety, can play as significant a role as the loop effect (from electromagnetic induction) in the heating of EEG electrodes, and therefore wire lengths that are odd multiples of ¼ RF wavelength should be avoided. These results have important implications for the design of EEG electrodes and MRI studies as they help to minimize the risk to patients undergoing MRI with EEG electrodes in place.
Vadim Ratner, Yi Gao, Hedok Lee, Rena Elkin, Maiken Nedergaard, Helene Benveniste, and Allen Tannenbaum. 2017. “Cerebrospinal and Interstitial Fluid Transport via the Glymphatic Pathway Modeled by Optimal Mass Transport.” Neuroimage, 152, Pp. 530-537.Abstract
The glymphatic pathway is a system which facilitates continuous cerebrospinal fluid (CSF) and interstitial fluid (ISF) exchange and plays a key role in removing waste products from the rodent brain. Dysfunction of the glymphatic pathway may be implicated in the pathophysiology of Alzheimer's disease. Intriguingly, the glymphatic system is most active during deep wave sleep general anesthesia. By using paramagnetic tracers administered into CSF of rodents, we previously showed the utility of MRI in characterizing a macroscopic whole brain view of glymphatic transport but we have yet to define and visualize the specific flow patterns. Here we have applied an alternative mathematical analysis approach to a dynamic time series of MRI images acquired every 4min over ∼3h in anesthetized rats, following administration of a small molecular weight paramagnetic tracer into the CSF reservoir of the cisterna magna. We use Optimal Mass Transport (OMT) to model the glymphatic flow vector field, and then analyze the flow to find the network of CSF-ISF flow channels. We use 3D visualization computational tools to visualize the OMT defined network of CSF-ISF flow channels in relation to anatomical and vascular key landmarks from the live rodent brain. The resulting OMT model of the glymphatic transport network agrees largely with the current understanding of the glymphatic transport patterns defined by dynamic contrast-enhanced MRI revealing key CSF transport pathways along the ventral surface of the brain with a trajectory towards the pineal gland, cerebellum, hypothalamus and olfactory bulb. In addition, the OMT analysis also revealed some interesting previously unnoticed behaviors regarding CSF transport involving parenchymal streamlines moving from ventral reservoirs towards the surface of the brain, olfactory bulb and large central veins.

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