In this note, we combined pediatric sarcoma data from Columbia University with adult sarcoma data collected from TCGA, in order to see if one can automatically discern a unique pediatric cluster in the combined data set. Using a novel clustering pipeline based on optimal transport theory, this turned out to be the case. The overall methodology may find uses for the classification of data from other biological networking problems.
Diffusion MRI tractography is increasingly used in pre-operative neurosurgical planning to visualize critical fiber tracts. However, a major challenge for conventional tractography, especially in patients with brain tumors, is tracing fiber tracts that are affected by vasogenic edema, which increases water content in the tissue and lowers diffusion anisotropy. One strategy for improving fiber tracking is to use a tractography method that is more sensitive than the traditional single-tensor streamline tractography. We performed experiments to assess the performance of two-tensor unscented Kalman filter (UKF) tractography in edema. UKF tractography fits a diffusion model to the data during fiber tracking, taking advantage of prior information from the previous step along the fiber. We studied UKF performance in a synthetic diffusion MRI digital phantom with simulated edema and in retrospective data from two neurosurgical patients with edema affecting the arcuate fasciculus and corticospinal tracts. We compared the performance of several tractography methods including traditional streamline, UKF single-tensor, and UKF two-tensor. To provide practical guidance on how the UKF method could be employed, we evaluated the impact of using various seed regions both inside and outside the edematous regions, as well as the impact of parameter settings on the tractography sensitivity. We quantified the sensitivity of different methods by measuring the percentage of the patient-specific fMRI activation that was reached by the tractography. We expected that diffusion anisotropy threshold parameters, as well as the inclusion of a free water model, would significantly influence the reconstruction of edematous WM fiber tracts, because edema increases water content in the tissue and lowers anisotropy. Contrary to our initial expectations, varying the fractional anisotropy threshold and including a free water model did not affect the UKF two-tensor tractography output appreciably in these two patient datasets. The most effective parameter for increasing tracking sensitivity was the generalized anisotropy (GA) threshold, which increased the length of tracked fibers when reduced to 0.075. In addition, the most effective seeding strategy was seeding in the whole brain or in a large region outside of the edema. Overall, the main contribution of this study is to provide insight into how UKF tractography can work, using a two-tensor model, to begin to address the challenge of fiber tract reconstruction in edematous regions near brain tumors.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.