We propose a non-parametric approach for characterizing heterogeneous diseases in large-scale studies. We target diseases where multiple types of pathology present simultaneously in each subject and a more severe disease manifests as a higher level of tissue destruction. For each subject, we model theof local image descriptors as samples generated by an unknown subject-specific probability density. Instead of approximating the probability density via a parametric family, we propose to side step the parametric inference by directly estimating the divergence between subject densities. Our method maps the collection of local image descriptors to a signaturethat is used to predict a clinical measurement. We are able to interpret the prediction of the clinical variable in the population and individual levels by carefully studying the divergences. We illustrate an application this method on simulated data as well as on a large-scale lung CT study of Chronic Obstructive Pulmonary Disease (COPD). Our approach outperforms classical methods on both simulated and COPD data and demonstrates the state-of-the-art prediction on an important physiologic measure of airflow (the forced respiratory volume in one second, FEV1).

We combined diffusion tension imaging (DTI) of prefrontal white matter integrity and neuropsychological measures to examine the functional neuroanatomy of human intelligence. Healthy participants completed the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III) along with neuropsychological tests of attention and executive control, as measured by Trail Making Test (TMT) and Wisconsin Card Sorting Test (WCST). Stochastic tractography, considered the most effective DTI method, quantified white matter integrity of the medial orbital frontal cortex (mOFC) and rostral anterior cingulate cortex (rACC) circuitry. Based on prior studies, we hypothesized that posterior mOFC-rACC connections may play a key structural role linking attentional control processes and intelligence. Behavioral results provided strong support for this hypothesis, specifically linking attentional control processes, measured by Trails B and WCST perseverative errors, to intelligent quotient (IQ). Hierarchical regression results indicated left posterior mOFC-rACC fractional anisotropy (FA) and Trails B performance time, but not WCST perseverative errors, each contributed significantly to IQ, accounting for approximately 33.95-51.60% of the variance in IQ scores. These findings suggested that left posterior mOFC-rACC white matter connections may play a key role in supporting the relationship of executive functions of attentional control and general intelligence in healthy cognition.

Using electroencephalography (EEG) to elucidate the spontaneous activation of brain resting-state networks (RSNs) is nontrivial as the signal of interest is of low amplitude and it is difficult to distinguish the underlying neural sources. Using the principles of electric field topographical analysis, it is possible to estimate the meta-stable states of the brain (i.e., the resting-state topographies, so-called microstates). We estimated seven resting-state topographies explaining the EEG data set with k-means clustering (N = 164, 256 electrodes). Using a method specifically designed to localize the sources of broadband EEG scalp topographies by matching sensor and source space temporal patterns, we demonstrated that we can estimate the EEG RSNs reliably by measuring the reproducibility of our findings. After subtracting their mean from the seven EEG RSNs, we identified seven state-specific networks. The mean map includes regions known to be densely anatomically and functionally connected (superior frontal, superior parietal, insula, and anterior cingulate cortices). While the mean map can be interpreted as a "router," crosslinking multiple functional networks, the seven state-specific RSNs partly resemble and extend previous functional magnetic resonance imaging-based networks estimated as the hemodynamic correlates of four canonical EEG microstates.

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.

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.

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.

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 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.

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.

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.