Publications by Year: 2017

2017
Essayed WI, Zhang F, Unadkat P, Cosgrove RG, Golby AJ, O'Donnell LJ. White Matter Tractography for Neurosurgical Planning: A Topography-based Review of the Current State of the Art. Neuroimage Clin. 2017;15 :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.
Herrlich M, Tavakol P, Black D, Wenig D, Rieder C, Malaka R, Kikinis R. Instrument-mounted Displays for Reducing Cognitive Load during Surgical Navigation. Int J Comput Assist Radiol Surg. 2017;12 (9) :1599-1605.Abstract
PURPOSE: Surgical navigation systems rely on a monitor placed in the operating room to relay information. Optimal monitor placement can be challenging in crowded rooms, and it is often not possible to place the monitor directly beside the situs. The operator must split attention between the navigation system and the situs. We present an approach for needle-based interventions to provide navigational feedback directly on the instrument and close to the situs by mounting a small display onto the needle. METHODS: By mounting a small and lightweight smartwatch display directly onto the instrument, we are able to provide navigational guidance close to the situs and directly in the operator's field of view, thereby reducing the need to switch the focus of view between the situs and the navigation system. We devise a specific variant of the established crosshair metaphor suitable for the very limited screen space. We conduct an empirical user study comparing our approach to using a monitor and a combination of both. RESULTS: Results from the empirical user study show significant benefits for cognitive load, user preference, and general usability for the instrument-mounted display, while achieving the same level of performance in terms of time and accuracy compared to using a monitor. CONCLUSION: We successfully demonstrate the feasibility of our approach and potential benefits. With ongoing technological advancements, instrument-mounted displays might complement standard monitor setups for surgical navigation in order to lower cognitive demands and for improved usability of such systems.
Koppelmans V, Pasternak O, Bloomberg JJ, Dios YDE, Wood SJ, Riascos R, Reuter-Lorenz PA, Kofman IS, Mulavara AP, Seidler RD. Intracranial Fluid Redistribution but No White Matter Microstructural Changes During a Spaceflight Analog. Sci Rep. 2017;7 (1) :3154.Abstract
The neural correlates of spaceflight-induced sensorimotor impairments are unknown. Head down-tilt bed rest (HDBR) serves as a microgravity analog because it mimics the headward fluid shift and axial body unloading of spaceflight. We investigated focal brain white matter (WM) changes and fluid shifts during 70 days of 6° HDBR in 16 subjects who were assessed pre (2x), during (3x), and post-HDBR (2x). Changes over time were compared to those in control subjects (n = 12) assessed four times over 90 days. Diffusion MRI was used to assess WM microstructure and fluid shifts. Free-Water Imaging was used to quantify distribution of intracranial extracellular free water (FW). Additionally, we tested whether WM and FW changes correlated with changes in functional mobility and balance measures. HDBR resulted in FW increases in fronto-temporal regions and decreases in posterior-parietal regions that largely recovered by two weeks post-HDBR. WM microstructure was unaffected by HDBR. FW decreases in the post-central gyrus and precuneus correlated negatively with balance changes. We previously reported that gray matter increases in these regions were associated with less HDBR-induced balance impairment, suggesting adaptive structural neuroplasticity. Future studies are warranted to determine causality and underlying mechanisms.
Nilsson M, Lasič S, Drobnjak I, Topgaard D, Westin C-F. Resolution Limit of Cylinder Diameter Estimation by Diffusion MRI: The Impact of Gradient Waveform and Orientation Dispersion. NMR Biomed. 2017;30 (7).Abstract
Diffusion MRI has been proposed as a non-invasive technique for axonal diameter mapping. However, accurate estimation of small diameters requires strong gradients, which is a challenge for the transition of the technique from preclinical to clinical MRI scanners, since these have weaker gradients. In this work, we develop a framework to estimate the lower bound for accurate diameter estimation, which we refer to as the resolution limit. We analyse only the contribution from the intra-axonal space and assume that axons can be represented by impermeable cylinders. To address the growing interest in using techniques for diffusion encoding that go beyond the conventional single diffusion encoding (SDE) sequence, we present a generalised analysis capable of predicting the resolution limit regardless of the gradient waveform. Using this framework, waveforms were optimised to minimise the resolution limit. The results show that, for parallel cylinders, the SDE experiment is optimal in terms of yielding the lowest possible resolution limit. In the presence of orientation dispersion, diffusion encoding sequences with square-wave oscillating gradients were optimal. The resolution limit for standard clinical MRI scanners (maximum gradient strength 60-80 mT/m) was found to be between 4 and 8 μm, depending on the noise levels and the level of orientation dispersion. For scanners with a maximum gradient strength of 300 mT/m, the limit was reduced to between 2 and 5 μm.
Balasubramanian M, Wells WM, Ives JR, Britz P, Mulkern RV, Orbach DB. RF Heating of Gold Cup and Conductive Plastic Electrodes during Simultaneous EEG and MRI. Neurodiagn J. 2017;57 (1) :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.
Black D, Hansen C, Nabavi A, Kikinis R, Hahn H. A Survey of Auditory Display in Image-guided Interventions. Int J Comput Assist Radiol Surg. 2017;12 (10) :1665-76.Abstract
PURPOSE: This article investigates the current state of the art of the use of auditory display in image-guided medical interventions. Auditory display is a means of conveying information using sound, and we review the use of this approach to support navigated interventions. We discuss the benefits and drawbacks of published systems and outline directions for future investigation. METHODS: We undertook a review of scientific articles on the topic of auditory rendering in image-guided intervention. This includes methods for avoidance of risk structures and instrument placement and manipulation. The review did not include auditory display for status monitoring, for instance in anesthesia. RESULTS: We identified 15 publications in the course of the search. Most of the literature (60%) investigates the use of auditory display to convey distance of a tracked instrument to an object using proximity or safety margins. The remainder discuss continuous guidance for navigated instrument placement. Four of the articles present clinical evaluations, 11 present laboratory evaluations, and 3 present informal evaluation (2 present both laboratory and clinical evaluations). CONCLUSION: Auditory display is a growing field that has been largely neglected in research in image-guided intervention. Despite benefits of auditory displays reported in both the reviewed literature and non-medical fields, adoption in medicine has been slow. Future challenges include increasing interdisciplinary cooperation with auditory display investigators to develop more meaningful auditory display designs and comprehensive evaluations which target the benefits and drawbacks of auditory display in image guidance.
Tax CMW, Westin C-F, Dela Haije T, Fuster A, Viergever MA, Calabrese E, Florack L, Leemans A. Quantifying the Brain's Sheet Structure with Normalized Convolution. Med Image Anal. 2017;39 :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.
Nenning K-H, Liu H, Ghosh SS, Sabuncu MR, Schwartz E, Langs G. Diffeomorphic Functional Brain Surface Alignment: Functional Demons. Neuroimage. 2017;156 :456-65.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.
Bernal-Rusiel JL, Rannou N, Gollub RL, Pieper S, Murphy S, Robertson R, Grant PE, Pienaar R. Reusable Client-Side JavaScript Modules for Immersive Web-Based Real-Time Collaborative Neuroimage Visualization. Front Neuroinform. 2017;11 :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.
Rydhög AS, Szczepankiewicz F, Wirestam R, Ahlgren A, Westin C-F, Knutsson L, Pasternak O. Separating Blood and Water: Perfusion and Free Water Elimination from Diffusion MRI in the Human Brain. Neuroimage. 2017;156 :423-34.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.
Ou Y, Zöllei L, Retzepi K, Castro V, Bates SV, Pieper S, Andriole KP, Murphy SN, Gollub RL, Grant PE. Using Clinically Acquired MRI to Construct Age-specific Atlases: Quantifying Spatiotemporal ADC Changes from Birth to 6-year Old. Hum Brain Mapp. 2017;38 (6) :3052-68.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.
Halle M, Demeusy V, Kikinis R. The Open Anatomy Browser: A Collaborative Web-Based Viewer for Interoperable Anatomy Atlases. Front Neuroinform. 2017;11 :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.

Black D, Hettig J, Luz M, Hansen C, Kikinis R, Hahn H. Auditory Feedback to Support Image-Guided Medical Needle Placement. Int J Comput Assist Radiol Surg. 2017;12 (9) :1655-63.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.
Chen X, Xu L, Wang H, Wang F, Wang Q, Kikinis R. Development of a Surgical Navigation System Based on 3D Slicer for Intraoperative Implant Placement Surgery. Med Eng Phys. 2017;41 :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.

Herberthson M, Özarslan E, Knutsson H, Westin C-F. Dynamics of Local Magnetization in the Eigenbasis of the Bloch-Torrey Operator. J Chem Phys. 2017;146 (12) :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.

Albi A, Pasternak O, Minati L, Marizzoni M, Bartrés-Faz D, Bargalló N, Bosch B, Rossini PM, Marra C, Müller B, et al. 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. 2017;38 (1) :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.

Shaffer JJ, Ghayoor A, Long JD, Kim RE-Y, Lourens S, O'Donnell LJ, Westin C-F, Rathi Y, Magnotta V, Paulsen JS, et al. Longitudinal Diffusion Changes in Prodromal and Early HD: Evidence of White-matter Tract Deterioration. Hum Brain Mapp. 2017;38 (3) :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. 

Ning L, Setsompop K, Westin C-F, Rathi Y. New Insights about Time-varying Diffusivity and its Estimation from Diffusion MRI. Magn Reson Med. 2017;78 (2) :763-74.Abstract

PURPOSE: Characterizing the relation between the applied gradient sequences and the measured diffusion MRI signal is important for estimating the time-dependent diffusivity, which provides important information about the microscopic tissue structure. THEORY AND METHODS: In this article, we extend the classical theory of Stepišnik for measuring time-dependent diffusivity under the Gaussian phase approximation. In particular, we derive three novel expressions which represent the diffusion MRI signal in terms of the mean-squared displacement, the instantaneous diffusivity, and the velocity autocorrelation function. We present the explicit signal expressions for the case of single diffusion encoding and oscillating gradient spin-echo sequences. Additionally, we also propose three different models to represent time-varying diffusivity and test them using Monte-Carlo simulations and in vivo human brain data. RESULTS: The time-varying diffusivities are able to distinguish the synthetic structures in the Monte-Carlo simulations. There is also strong statistical evidence about time-varying diffusivity from the in vivo human data set. CONCLUSION: The proposed theory provides new insights into our understanding of the time-varying diffusivity using different gradient sequences. The proposed models for representing time-varying diffusivity can be utilized to study time-varying diffusivity using in vivo human brain diffusion MRI data. 

Ning L, Özarslan E, Westin C-F, Rathi Y. Precise Inference and Characterization of Structural Organization (PICASO) of Tissue from Molecular Diffusion. Neuroimage. 2017;146 :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.

Pujol S, Cabeen R, Sébille SB, Yelnik J, François C, Fernandez Vidal S, Karachi C, Zhao Y, Cosgrove RG, Jannin P, et al. In vivo Exploration of the Connectivity between the Subthalamic Nucleus and the Globus Pallidus in the Human Brain using Multi-Fiber Tractography. Front Neuroanat. 2017;10 :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.

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