Offline fusion of co-registered intravascular ultrasound and frequency domain optical coherence tomography images for the analysis of human atherosclerotic plaques

To demonstrate the feasibility and potential usefulness of an offline fusion of matched optical coherence tomography (OCT) and intravascular ultrasound (IVUS)/virtual histology (IVUS-VH) images.

Thought-Action Fusion and Neutralization Behavior

This study presents a new inventory to assess thought-action fusion (TAF). 160 college students ages 18 to 22 (M = 19.17, SD = 1.11) completed the new Modified Thought Action Scale (MTAFS). Results indicated high internal consistency in the MTAFS (Cronbach’s α = .95). A principal component analysis suggested a three factor solution of TAF-Moral (TAFM), TAFLikelihood (TAFL), and TAF-Harm avoidance-Positive (TAFHP) all with eigenvalues above 1, and factor loadings above .4. A second study examined the association between TAF, obsessivecompulsive and anxiety tendencies after the activation of TAF-like thought processes in a nonclinical sample (n=76). Subjects were randomly assigned to one of three treatment groups intended to provoke TAFL-self, TAFL-other, and TAF moral thought processes. Stepwise regression analyses revealed: 1) the Obsessive-Compulsive Inventory subscales Neutralizing and Ordering significantly predicted instructed neutralization behavior (INB) in non-clinical participants; 2) TAF-Likelihood contributed significant unique variance in INB. These findings suggest that the provocation of neutralization behavior may be mediated by specific subsets of TAF and obsessive-compulsive tendencies.

Multimodal Integration in Statistical Learning: Evidence from the McGurk Illusion

Recent advances in the field of statistical learning have established that learners are able to track regularities of multimodal stimuli, yet it is unknown whether the statistical computations are performed on integrated representations or on separate, unimodal representations. In the present study, we investigated the ability of adults to integrate audio and visual input during statistical learning. We presented learners with a speech stream synchronized with a video of a speaker's face. In the critical condition, the visual (e.g., /gi/) and auditory (e.g., /mi/) signals were occasionally incongruent, which we predicted would produce the McGurk illusion, resulting in the perception of an audiovisual syllable (e.g., /ni/). In this way, we used the McGurk illusion to manipulate the underlying statistical structure of the speech streams, such that perception of these illusory syllables facilitated participants' ability to segment the speech stream. Our results therefore demonstrate that participants can integrate audio and visual input to perceive the McGurk illusion during statistical learning. We interpret our findings as support for modality-interactive accounts of statistical learning.

Different duration of at-risk mental state associated with neurofunctional abnormalities. A multimodal imaging study

Objectives: Neurofunctional alterations are correlates of vulnerability to psychosis, as well as of the disorder itself. How these abnormalities relate to different probabilities for later transition to psychosis is unclear. We investigated vulnerability- versus disease-related versus resilience biomarkers of psychosis during working memory (WM) processing in individuals with an at-risk mental state (ARMS). Experimental design: Patients with “first-episode psychosis” (FEP, n = 21), short-term ARMS (ARMS-ST, n = 17), long-term ARMS (ARMS-LT, n = 16), and healthy controls (HC, n = 20) were investigated with an n-back WM task. We examined functional magnetic resonance imaging (fMRI) and structural magnetic resonance imaging (sMRI) data in conjunction using biological parametric mapping (BPM) toolbox. Principal observations: There were no differences in accuracy, but the FEP and the ARMS-ST group had longer reaction times compared with the HC and the ARMS-LT group. With the 2-back > 0-back contrast, we found reduced functional activation in ARMS-ST and FEP compared with the HC group in parietal and middle frontal regions. Relative to ARMS-LT individuals, FEP patients showed decreased activation in the bilateral inferior frontal gyrus and insula, and in the left prefrontal cortex. Compared with the ARMS-LT, the ARMS-ST subjects showed reduced activation in the right inferior frontal gyrus and insula. Reduced insular and prefrontal activation was associated with gray matter volume reduction in the same area in the ARMS-LT group. Conclusions: These findings suggest that vulnerability to psychosis was associated with neurofunctional alterations in fronto-temporo-parietal networks in a WM task. Neurofunctional differences within the ARMS were related to different duration of the prodromal state and resilience factors

An early warning system for hypoglycemic/hyperglycemic events based on fusion of adaptive prediction models

Early warning of future hypoglycemic and hyperglycemic events can improve the safety of type 1 diabetes mellitus (T1DM) patients. The aim of this study is to design and evaluate a hypoglycemia/hyperglycemia early warning system (EWS) for T1DM patients under sensor-augmented pump (SAP) therapy.

The GPVI - Fc Fusion Protein Revacept Reduces Thrombus Formation and Improves Vascular Dysfunction in Atherosclerosis without Any Impact on Bleeding Times

Glycoprotein VI (GPVI) is a key platelet receptor which mediates plaque-induced platelet activation and consecutive atherothrombosis, but GPVI is also involved in platelet-mediated atheroprogression. Therefore, interference in GPVI-mediated platelet activation has the potential to combine short-term and long-term beneficial effects, specificity and safety especially regarding bleeding complications.

Tissue-transplant fusion and vascularization of myocardial microtissues and macrotissues implanted into chicken embryos and rats

Cell-based therapies and tissue engineering initiatives are gathering clinical momentum for next-generation treatment of tissue deficiencies. By using gravity-enforced self-assembly of monodispersed primary cells, we have produced adult and neonatal rat cardiomyocyte-based myocardial microtissues that could optionally be vascularized following coating with human umbilical vein endothelial cells (HUVECs). Within myocardial microtissues, individual cardiomyocytes showed native-like cell shape and structure, and established electrochemical coupling via intercalated disks. This resulted in the coordinated beating of microtissues, which was recorded by means of a multi-electrode complementary metal-oxide-semiconductor microchip. Myocardial microtissues (microm3 scale), coated with HUVECs and cast in a custom-shaped agarose mold, assembled to coherent macrotissues (mm3 scale), characterized by an extensive capillary network with typical vessel ultrastructures. Following implantation into chicken embryos, myocardial microtissues recruited the embryo's capillaries to functionally vascularize the rat-derived tissue implant. Similarly, transplantation of rat myocardial microtissues into the pericardium of adult rats resulted in time-dependent integration of myocardial microtissues and co-alignment of implanted and host cardiomyocytes within 7 days. Myocardial microtissues and custom-shaped macrotissues produced by cellular self-assembly exemplify the potential of artificial tissue implants for regenerative medicine.

Harvesting local cylinder autograft from adjacent vertebral body for anterior lumbar interbody fusion: surgical technique, operative feasibility and preliminary clinical results

Autogenous iliac crest has long served as the gold standard for anterior lumbar arthrodesis although added morbidity results from the bone graft harvest. Therefore, femoral ring allograft, or cages, have been used to decrease the morbidity of iliac crest bone harvesting. More recently, an experimental study in the animal showed that harvesting local bone from the anterior vertebral body and replacing the void by a radio-opaque beta-tricalcium phosphate plug was a valid concept. However, such a concept precludes theoretically the use of posterior pedicle screw fixation. At one institution a consecutive series of 21 patients underwent single- or multiple-level circumferential lumbar fusion with anterior cages and posterior pedicle screws. All cages were filled with cancellous bone harvested from the adjacent vertebral body, and the vertebral body defect was filled with a beta-tricalcium phosphate plug. The indications for surgery were failed conservative treatment of a lumbar degenerative disc disease or spondylolisthesis. The purpose of this study, therefore, was to report on the surgical technique, operative feasibility, safety, benefits, and drawbacks of this technique with our primary clinical experience. An independent researcher reviewed all data that had been collected prospectively from the onset of the study. The average age of the patients was 39.9 (26-57) years. Bone grafts were successfully harvested from 28 vertebral bodies in all but one patient whose anterior procedure was aborted due to difficulty in freeing the left common iliac vein. This case was converted to a transforaminal interbody fusion (TLIF). There was no major vascular injury. Blood loss of the anterior procedure averaged 250 ml (50-350 ml). One tricalcium phosphate bone plug was broken during its insertion, and one endplate was broken because of wrong surgical technique, which did not affect the final outcome. One patient had a right lumbar plexopathy that was not related to this special technique. There was no retrograde ejaculation, infection or pseudoarthrosis. One patient experienced a deep venous thrombosis. At the last follow up (mean 28 months) all patients had a solid lumbar spine fusion. At the 6-month follow up, the pain as assessed on the visual analog scale (VAS) decreased from 6.9 to 4.5 (33% decrease), and the Oswestry disability index (ODI) reduced from 48.0 to 31.7 with a 34% reduction. However, at 2 years follow up there was a trend for increase in the ODI (35) and VAS (5). The data in this study suggest that harvesting a cylinder of autograft from the adjacent vertebral body is safe and efficient. Filling of the void defect with a beta-tricalcium phosphate plug does not preclude the use of posterior pedicle screw stabilization.

Multimodal augmented reality system for surgical microscopy

Image-guided, computer-assisted neurosurgery has emerged to improve localization and targeting, to provide a better anatomic definition of the surgical field, and to decrease invasiveness. Usually, in image-guided surgery, a computer displays the surgical field in a CT/MR environment, using axial, coronal or sagittal views, or even a 3D representation of the patient. Such a system forces the surgeon to look away from the surgical scene to the computer screen. Moreover, this kind of information, being pre-operative imaging, can not be modified during the operation, so it remains valid for guidance in the first stage of the surgical procedure, and mainly for rigid structures like bones. In order to solve the two constraints mentioned before, we are developing an ultrasoundguided surgical microscope. Such a system takes the advantage that surgical microscopy and ultrasound systems are already used in neurosurgery, so it does not add more complexity to the surgical procedure. We have integrated an optical tracking device in the microscope and an augmented reality overlay system with which we avoid the need to look away from the scene, providing correctly aligned surgical images with sub-millimeter accuracy. In addition to the standard CT and 3D views, we are able to track an ultrasound probe, and using a previous calibration and registration of the imaging, the image obtained is correctly projected to the overlay system, so the surgeon can always localize the target and verify the effects of the intervention. Several tests of the system have been already performed to evaluate the accuracy, and clinical experiments are currently in progress in order to validate the clinical usefulness of the system.

Synergistic inhibition in cell-cell fusion mediated by the matrix and nucleocapsid protein of canine distemper virus

Canine distemper virus (CDV) causes a chronic, demyelinating, progressive or relapsing neurological disease in dogs, because CDV persists in the CNS. Persistence of virulent CDV, such as the A75/17 strain has been reproduced in cell cultures where it is associated with a non-cytolytic infection with very limited cell-cell fusion. This is in sharp contrast to attenuated CDV infection in cell cultures, such as the Onderstepoort (OP) CDV strain, which produces extensive fusion activity and cytolysis. Fusion efficiency may be determined by the structure of the viral fusion protein per se but also by its interaction with other structural proteins of CDV. This was studied by combining genes derived from persistent and non-persistent CDV strains in transient transfection experiments. It was found that fusion efficiency was markedly attenuated by the structure of the fusion protein of the neurovirulent A75/17-CDV. Moreover, we showed that the interaction of the surface glycoproteins with the M protein of the persistent strain greatly influenced fusion activity. Site directed mutagenesis showed that the c-terminus of the M protein is of particular importance in this respect. Interestingly, although the nucleocapsid protein alone did not affect F/H-induced cell-cell fusion, maximal inhibition occurred when the latter was added to combined glycoproteins with matrix protein. Thus, the present study suggests that very limited fusogenicity in virulent CDV infection, which favours persistence by limiting cell destruction involves complex interactions between all viral structural proteins.

Signal peptide and helical bundle domains of virulent canine distemper virus fusion protein restrict fusogenicity

Persistence in canine distemper virus (CDV) infection is correlated with very limited cell-cell fusion and lack of cytolysis induced by the neurovirulent A75/17-CDV compared to that of the cytolytic Onderstepoort vaccine strain. We have previously shown that this difference was at least in part due to the amino acid sequence of the fusion (F) protein (P. Plattet, J. P. Rivals, B. Zuber, J. M. Brunner, A. Zurbriggen, and R. Wittek, Virology 337:312-326, 2005). Here, we investigated the molecular mechanisms of the neurovirulent CDV F protein underlying limited membrane fusion activity. By exchanging the signal peptide between both F CDV strains or replacing it with an exogenous signal peptide, we demonstrated that this domain controlled intracellular and consequently cell surface protein expression, thus indirectly modulating fusogenicity. In addition, by serially passaging a poorly fusogenic virus and selecting a syncytium-forming variant, we identified the mutation L372W as being responsible for this change of phenotype. Intriguingly, residue L372 potentially is located in the helical bundle domain of the F(1) subunit. We showed that this mutation drastically increased fusion activity of F proteins of both CDV strains in a signal peptide-independent manner. Due to its unique structure even among morbilliviruses, our findings with respect to the signal peptide are likely to be specifically relevant to CDV, whereas the results related to the helical bundle add new insights to our growing understanding of this class of F proteins. We conclude that different mechanisms involving multiple domains of the neurovirulent A75/17-CDV F protein act in concert to limit fusion activity, preventing lysis of infected cells, which ultimately may favor viral persistence.

Cardiac image fusion from stand-alone SPECT and CT: clinical experience

Myocardial perfusion imaging with SPECT (SPECT-MPI) and 64-slice CT angiography (CTA) are both established techniques for the noninvasive evaluation of coronary artery disease (CAD). Three-dimensional (3D) SPECT/CT image fusion may offer an incremental diagnostic value by integrating both sets of information. We report our first clinical experiences with fused 3D SPECT/CT in CAD patients. METHODS: Thirty-eight consecutive patients with at least 1 perfusion defect on SPECT-MPI (1-d adenosine stress/rest SPECT with (99m)Tc-tetrofosmin) and 64-slice CTA were included. 3D volume-rendered fused SPECT/CT images were generated and compared with the findings from the side-by-side analysis with regard to coronary lesion interpretation by assigning the perfusion defects to their corresponding coronary lesion. RESULTS: The fused SPECT/CT images added information on pathophysiologic lesion severity in 27 coronary stenoses (22%) of 12 patients (29%) (P<0.001). Among 40 equivocal lesions on side-by-side analysis, the fused interpretation confirmed hemodynamic significance in 14 lesions and excluded functional relevance in 10 lesions. In 3 lesions, assignment of perfusion defect and coronary lesion appeared to be reliable on side-by-side analysis but proved to be inaccurate on fused interpretation. Added diagnostic information by SPECT/CT was more commonly found in patients with stenoses of small vessels (P=0.004) and involvement of diagonal branches (P=0.01). CONCLUSION: In addition to being intuitively convincing, 3D SPECT/CT fusion images in CAD may provide added diagnostic information on the functional relevance of coronary artery lesions.