Background: We describe a suite of tools and methods that form a core set of capabilities for researchers and clinical investigators to evaluate multiple analytical pipelines and quantify sensitivity and variability of the results while conducting large-scale studies in investigative pathology and oncology. The overarching objective of the current investigation is to address the challenges of large data sizes and high computational demands. Results: The proposed tools and methods take advantage of state-of-the-art parallel machines and efficient content-based image searching strategies. The content based image retrieval (CBIR) algorithms can quickly detect and retrieve image patches similar to a query patch using a hierarchical analysis approach. The analysis component based on high performance computing can carry out consensus clustering on 500,000 data points using a large shared memory system. Conclusions: Our work demonstrates efficient CBIR algorithms and high performance computing can be leveraged for efficient analysis of large microscopy images to meet the challenges of clinically salient applications in pathology. These technologies enable researchers and clinical investigators to make more effective use of the rich informational content contained within digitized microscopy specimens.
Objective: We conducted intraoperative measurements of tremor during DBS containing short pauses (≤50. ms) to determine if there is a minimum pause duration that preserves tremor suppression.
Methods: Nine subjects with ET and thalamic DBS participated during IPG replacement surgery. Patterns of DBS included regular 130. Hz stimulation interrupted by 0, 15, 25 or 50. ms pauses. The same patterns were applied to a model of the thalamic network to quantify effects of pauses on activity of model neurons.
Results: All patterns of DBS decreased tremor relative to 'off'. Patterns with pauses generated less tremor reduction than regular high frequency DBS. The model revealed that rhythmic burst-driver inputs to thalamus were masked during DBS, but pauses in stimulation allowed propagation of bursting activity. The mean firing rate of bursting-type model neurons as well as the firing pattern entropy of model neurons were both strongly correlated with tremor power across stimulation conditions.
Conclusions: The temporal pattern of stimulation influences the efficacy of thalamic DBS. Pauses in stimulation resulted in decreased tremor suppression indicating that masking of pathological bursting is a mechanism of thalamic DBS for tremor.
Significance: Pauses in stimulation decreased the efficacy of open-loop DBS for suppression of tremor.
Computed tomography (CT) slices are combined with computational fluid dynamics (CFD) to simulate the flow patterns in a human left coronary artery. The vascular model was reconstructed from CT slices scanned from a healthy volunteer in vivo. The spatial resolution of the slices is 0.6 × 0.6 × 0.625 mm so that geometrical details of the local wall surface of the vessel could be considered in the CFD modeling. This level of resolution is needed to investigate the wall shear stress (WSS) distribution, a factor generally recognized as a related to the atherogenesis. The WSS distributions on the main trunk and bifurcation of the left coronary artery of the model in one cardiac cycle are presented, and the results demonstrate that low and oscillating WSS is correlative with clinical observations of the atherosclerotic-prone sites in the left coronary artery.
We propose a simple method for reconstructing vascular trees from 3D images. Our algorithm extracts persistent maxima of the intensity on all axis-aligned 2D slices of the input image. The maxima concentrate along 1D intensity ridges, in particular along blood vessels. We build a forest connecting the persistent maxima with short edges. The forest tends to approximate the blood vessels present in the image, but also contains numerous spurious features and often fails to connect segments belonging to one vessel in low contrast areas. We improve the forest by applying simple geometric filters that trim short branches, fill gaps in blood vessels and remove spurious branches from the vascular tree to be extracted. Experiments show that our technique can be applied to extract coronary trees from heart CT scans.
BACKGROUND AND PURPOSE: Phase analysis of gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) has been validated as a reliable tool to assess left-ventricular (LV) mechanical dyssynchrony. The initial results were all confirmed from studies using technetium-99m (Tc-99m) sestamibi or tetrofosmin as the radiotracers. The purpose of this study was to evaluate the feasibility of phase analysis in thallium-201 (Tl-201) gated SPECT MPI. MATERIALS AND METHODS: Seventeen patients referred from a cardiology clinic for evaluation of coronary artery disease were studied. All patients underwent both Tl-201 and Tc-99m sestamibi gated SPECT MPI within 1 week. An additional 34 patients with Tl-201 gated SPECT and 22 patients with Tc-99m sestamibi gated SPECT, who had a low likelihood of coronary artery disease, normal LV function, and normal perfusion on MPI, were used as normal controls. LV dyssynchrony parameters, including phase standard deviation (PSD) and phase histogram bandwidth (PHB), were measured using a standard phase analysis tool and compared between Tl-201 and Tc-99m sestamibi images. RESULTS: The LV dyssynchrony parameters correlated well (r=0.93 for PSD and r=0.84 for PHB) between Tl-201 and Tc-99m sestamibi images. The dyssynchrony parameters of Tl-201 were significantly larger than those of Tc-99m sestamibi (PSD: 24.5±12.0 vs. 17.4±9.7, P<0.001; PHB: 74.7±35.5 vs. 50.6±25.0, P<0.001). In comparison with normal controls, Tl-201 and Tc-99m sestamibi images showed concordant results. CONCLUSION: LV dyssynchrony parameters correlated well between Tl-201 and Tc-99m sestamibi images, even though the values were significantly larger for Tl-201 than for Tc-99m sestamibi. Tl-201 images showed results similar to those of Tc-99m sestamibi in the diagnosis of LV dyssynchrony.
Diffusion tensor imaging (DTI), high angular resolution diffusion imaging (HARDI), and diffusion spectrum imaging (DSI) have been widely used in the neuroimaging field to examine the macro-scale fiber connection patterns in the cerebral cortex. However, the topographic and geometric relationships between diffusion imaging derived streamline fiber connection patterns and cortical folding patterns remain largely unknown. This paper specifically identifies and characterizes the U-shapes of diffusion imaging derived streamline fibers via a novel fiber clustering framework and examines their co-localization patterns with cortical sulci based on DTI, HARDI, and DSI datasets of human, chimpanzee and macaque brains. We verified the presence of these U-shaped streamline fibers that connect neighboring gyri by coursing around cortical sulci such as the central sulcus, pre-central sulcus, post-central sulcus, superior temporal sulcus, inferior frontal sulcus, and intra-parietal sulcus. This study also verified the existence of U-shape fibers across data modalities (DTI/HARDI/DSI) and primate species (macaque, chimpanzee and human), and suggests that the common pattern of U-shape fibers coursing around sulci is evolutionarily-preserved in cortical architectures.
Functional mitral regurgitation (FMR) is a significant complication of left ventricular dysfunction and strongly associated with a poor prognosis. In this study, we developed a patient-specific finite element (FE) model of the mitral apparatus in a FMR patient which included: both leaflets with thickness, annulus, chordae tendineae, and chordae insertions on the leaflets and origins on the papillary muscles. The FE model incorporated human age- and gender-matched anisotropic hyperelastic material properties, and MV closure at systole was simulated. The model was validated by comparing the FE results from valve closure simulation with the in vivo geometry of the MV at systole. It was found that the FE model could not replicate the in vivo MV geometry without the application of tethering pre-tension force in the chordae at diastole. Upon applying the pre-tension force and performing model optimization by adjusting the chordal length, position, and leaflet length, a good agreement between the FE model and the in vivo model was established. Not only were the chordal forces high at both diastole and systole, but the tethering force on the anterior papillary muscle was higher than that of the posterior papillary muscle, which resulted in an asymmetrical gap with a larger orifice area at the anterolateral commissure resulting in MR. The analyses further show that high peak stress and strain were found at the chordal insertions where large chordal tethering forces were found. This study shows that the pre-tension tethering force plays an important role in accurately simulating the MV dynamics in this FMR patient, particularly in quantifying the degree of leaflet coaptation and stress distribution. Due to the complexity of the disease, the patient-specific computational modeling procedure of FMR patients presented should be further evaluated using a large patient cohort. However, this study provides useful insights into the MV biomechanics of a FMR patient, and could serve as a tool to assist in pre-operative planning for MV repair or replacement surgical or interventional procedures.
Computational models of the heart's mitral valve (MV) exhibit potential for preoperative surgical planning in ischemic mitral regurgitation (IMR). However challenges exist in defining boundary conditions to accurately model the function and response of the chordae tendineae to both IMR and surgical annuloplasty repair. Towards this goal, a ground-truth data set was generated by quantifying the isolated effects of IMR and mitral annuloplasty on leaflet coaptation, regurgitation, and tethering forces of the anterior strut and posterior intermediary chordae tendineae. MVs were excised from ovine hearts (N = 15) and mounted in a pulsatile heart simulator which has been demonstrated to mimic the systolic MV geometry and coaptation of healthy and chronic IMR sheep. Strut and intermediary chordae from both MV leaflets (N = 4) were instrumented with force transducers. Tested conditions included a healthy control, IMR, oversized annuloplasty, true-sized annuloplasty, and undersized mitral annuloplasty. A2-P2 leaflet coaptation length, regurgitation, and chordal tethering were quantified and statistically compared across experimental conditions. MR was successfully simulated with significant increases in MR, tethering forces for each of the chordae, and decrease in leaflet coaptation (p < .05). Compared to the IMR condition, increasing levels of downsized annuloplasty significantly reduced regurgitation, increased coaptation, reduced posteromedial papillary muscle strut chordal forces, and reduced intermediary chordal forces from the anterolateral papillary muscle (p < .05). These results provide for the first time a novel comprehensive data set for refining the ability of computational MV models to simulate IMR and varying sizes of complete rigid ring annuloplasty.
Over the years, three-dimensional models of the mitral valve have generally been organized around a simplified anatomy. Leaflets have been typically modeled as membranes, tethered to discrete chordae typically modeled as one-dimensional, non-linear cables. Yet, recent, high-resolution medical images have revealed that there is no clear boundary between the chordae and the leaflets. In fact, the mitral valve has been revealed to be more of a webbed structure whose architecture is continuous with the chordae and their extensions into the leaflets. Such detailed images can serve as the basis of anatomically accurate, subject-specific models, wherein the entire valve is modeled with solid elements that more faithfully represent the chordae, the leaflets, and the transition between the two. These models have the potential to enhance our understanding of mitral valve mechanics and to re-examine the role of the mitral valve chordae, which heretofore have been considered to be ‘invisible’ to the fluid and to be of secondary importance to the leaflets. However, these new models also require a rethinking of modeling assumptions. In this study, we examine the conventional practice of loading the leaflets only and not the chordae in order to study the structural response of the mitral valve apparatus. Specifically, we demonstrate that fully resolved 3D models of the mitral valve require a fluid–structure interaction analysis to correctly load the valve even in the case of quasi-static mechanics. While a fluid–structure interaction mode is still more computationally expensive than a structural-only model, we also show that advances in GPU computing have made such models tractable.
by
Tyrone D. Cannon;
Frank Sun;
Sarah Jacobson McEwen;
Xenophon Papademetris;
George He;
Theo G. M. van Erp;
Aron Jacobson;
Carrie E. Bearden;
Elaine Walker;
Xiaoping Hu;
Lei Zhou;
Larry J. Seidman;
Heidi W. Thermenos;
Barbara Cornblatt;
Doreen M. Olvet;
Diana Perkins;
Aysenil Belger;
Kristin Cadenhead;
Ming Tsuang;
Heline Mirzakhanian;
Jean Addington;
Richard Frayne;
Scott W. Woods;
Thomas H. McGlashan;
R. Todd Constable;
Maolin Qiu;
Daniel H. Mathalon;
Paul Thompson;
Arthur W. Toga
Multisite longitudinal neuroimaging designs are used to identify differential brain structural change associated with onset or progression of disease. The reliability of neuroanatomical measurements over time and across sites is a crucial aspect of power in such studies. Prior work has found that while within-site reliabilities of neuroanatomical measurements are excellent, between-site reliability is generally more modest. Factors that may increase between-site reliability include standardization of scanner platform and sequence parameters and correction for between-scanner variations in gradient nonlinearities. Factors that may improve both between- and within-site reliability include use of registration algorithms that account for individual differences in cortical patterning and shape. In this study 8 healthy volunteers were scanned twice on successive days at 8 sites participating in the North American Prodrome Longitudinal Study (NAPLS). All sites employed 3 Tesla scanners and standardized acquisition parameters. Site accounted for 2 to 30% of the total variance in neuroanatomical measurements. However, site-related variations were trivial (<1%) among sites using the same scanner model and 12-channel coil or when correcting for between-scanner differences in gradient nonlinearity and scaling. Adjusting for individual differences in sulcal-gyral geometries yielded measurements with greater reliabilities than those obtained using an automated approach. Neuroimaging can be performed across multiple sites at the same level of reliability as at a single site, achieving within- and between-site reliabilities of 0.95 or greater for gray matter density in the majority of voxels in the prefrontal and temporal cortical surfaces as well as for the volumes of most subcortical structures.