Unified Framework for Development, Deployment and Robust Testing of Neuroimaging Algorithms

Developing both graphical and commandline user interfaces for neuroimaging algorithms requires considerable effort. Neuroimaging algorithms can meet their potential only if they can be easily and frequently used by their intended users. Deployment of a large suite of such algorithms on multiple platforms requires consistency of user interface controls, consistent results across various platforms and thorough testing. We present the design and implementation of a novel object-oriented framework that allows for rapid development of complex image analysis algorithms with many reusable components and the ability to easily add graphical user interface controls. Our framework also allows for simplified yet robust nightly testing of the algorithms to ensure stability and cross platform interoperability. All of the functionality is encapsulated into a software object requiring no separate source code for user interfaces, testing or deployment. This formulation makes our framework ideal for developing novel, stable and easy-to-use algorithms for medical image analysis and computer assisted interventions. The technological The framework has been both deployed at Yale and released for public use in the open source multi-platform image analysis software - BioImage Suite (bioimagesuite.org)

Intraoperative Real-Time Querying of White Matter Tracts During Frameless Stereotactic Neuronavigation

BACKGROUND: Brain surgery faces important challenges when trying to achieve maximum tumor resection while avoiding postoperative neurological deficits. OBJECTIVE: For surgeons to have optimal intraoperative information concerning white matter (WM) anatomy, we developed a platform that allows the intraoperative real-time querying of tractography data sets during frameless stereotactic neuronavigation. METHODS: Structural magnetic resonance imaging, functional magnetic resonance imaging, and diffusion tensor imaging were performed on 5 patients before they underwent lesion resection using neuronavigation. During the procedure, the tracked surgical tool tip position was transferred from the navigation system to the 3-dimensional Slicer software package, which used this position to seed the WM tracts around the tool tip location, rendering a geometric visualization of these tracts on the preoperative images previously loaded onto the navigation system. The clinical feasibility of this approach was evaluated in 5 cases of lesion resection. In addition, system performance was evaluated by measuring the latency between surgical tool tracking and visualization of the seeded WM tracts. RESULTS: Lesion resection was performed successfully in all 5 patients. The seeded WM tracts close to the lesion and other critical structures, as defined by the functional and structural images, were interactively visualized during the intervention to determine their spatial relationships relative to the lesion and critical cortical areas. Latency between tracking and visualization of tracts was less than a second for a fiducial radius size of 4 to 5 mm. CONCLUSION: Interactive tractography can provide an intuitive way to inspect critical WM tracts in the vicinity of the surgical region, allowing the surgeon to have increased intraoperative WM information to execute the planned surgical resection

Self-assembly of pH-responsive fluorinated dendrimer-based particulates for drug delivery and noninvasive imaging

a b s t r a c t Dendrimers are nanoscale macromolecules with well-defined branching chemical structures. Control over the architecture and function of these structures has enabled many advances in materials science and biomedical applications. Though dendrimers are directly synthesized by iteration of simple repetitive steps, generation of the larger, more complex structures required for many biomedical applications by covalent synthetic methods has been challenging. Here we demonstrate a spontaneous self-assembly of poly(amidoamine) dendrimers into complex nanoscopic and microscopic particulates following partial fluorination of the constituent dendrimer subunits. These dense particulates exhibit a stimulus-induced response to low external pH that causes their disassembly over time, enabling controlled release of encapsulated agents. In addition, we show that these assemblies offer a sufficiently high density of fluorine spins to enable detection of their site-specific accumulation in vivo b

Multisite reliability of MR-based functional connectivity

Recent years have witnessed an increasing number of multisite MRI functional connectivity (fcMRI) studies. While multisite studies are an efficient way to speed up data collection and increase sample sizes, especially for rare clinical populations, any effects of site or MRI scanner could ultimately limit power and weaken results. Little data exists on the stability of functional connectivity measurements across sites and sessions. In this study, we assess the influence of site and session on resting state functional connectivity measurements in a healthy cohort of traveling subjects (8 subjects scanned twice at each of 8 sites) scanned as part of the North American Prodrome Longitudinal Study (NAPLS). Reliability was investigated in three types of connectivity analyses: (1) seed-based connectivity with posterior cingulate cortex (PCC), right motor cortex (RMC), and left thalamus (LT) as seeds; (2) the intrinsic connectivity distribution (ICD), a voxel-wise connectivity measure; and (3) matrix connectivity, a whole-brain, atlas-based approach assessing connectivity between nodes. Contributions to variability in connectivity due to subject, site, and day-of-scan were quantified and used to assess between-session (test-retest) reliability in accordance with Generalizability Theory. Overall, no major site, scanner manufacturer, or day-of-scan effects were found for the univariate connectivity analyses; instead, subject effects dominated relative to the other measured factors. However, summaries of voxel-wise connectivity were found to be sensitive to site and scanner manufacturer effects. For all connectivity measures, although subject variance was three times the site variance, the residual represented 60–80% of the variance, indicating that connectivity differed greatly from scan to scan independent of any of the measured factors (i.e., subject, site, and day-of-scan). Thus, for a single 5 min scan, reliability across connectivity measures was poor (ICC=0.07–0.17), but increases with increasing scan duration (ICC=0.21–0.36 at 25 min). The limited effects of site and scanner manufacturer support the use of multisite studies, such as NAPLS, as a viable means of collecting data on rare populations and increasing power in univariate functional connectivity studies. However, the results indicate that aggregation of fcMRI data across longer scan durations is necessary to increase the reliability of connectivity estimates at the single-subject level

Neural Aspects of Sentence Comprehension: Syntactic Complexity, Reversibility, and Reanalysis

Broca's area is preferentially activated by reversible sentences with complex syntax, but various linguistic factors may be responsible for this finding, including syntactic movement, working-memory demands, and post hoc reanalysis. To distinguish between these, we tested the interaction of syntactic complexity and semantic reversibility in a functional magnetic resonance imaging study of sentence–picture matching. During auditory comprehension, semantic reversibility induced selective activation throughout the left perisylvian language network. In contrast, syntactic complexity (object-embedded vs. subject-embedded relative clauses) within reversible sentences engaged only the left inferior frontal gyrus (LIFG) and left precentral gyrus. Within irreversible sentences, only the LIFG was sensitive to syntactic complexity, confirming a unique role for this region in syntactic processing. Nonetheless, larger effects of reversibility itself occurred in the same regions, suggesting that full syntactic parsing may be a nonautomatic process applied as needed. Complex reversible sentences also induced enhanced signals in LIFG and left precentral regions on subsequent picture selection, but with additional recruitment of the right hemisphere homolog area (right inferior frontal gyrus) as well, suggesting that post hoc reanalysis of sentence structure, compared with initial comprehension, engages an overlapping but larger network of brain regions. These dissociable effects may offer a basis for studying the reorganization of receptive language function after brain damage