Nasal septum-derived chondroprogenitor cells control mandibular condylar resorption consequent to orthognathic surgery: a clinical trial.

Condylar resorption is an aggressive and disability form of temporomandibular joint (TMJ) degenerative disease, usually non-respondent to conservative or minimally invasive therapies and often leading to surgical intervention and prostheses implantation. This condition is also one of the most dreaded postoperative complications of orthognathic surgery, with severe cartilage erosion and loss of subchondral bone volume and mineral density, associated with a painful or not inflammatory processes. Because regenerative medicine has emerged as an alternative for orthopedic cases with advanced degenerative joint disease, we conducted a phase I/IIa clinical trial (U1111-1194-6997) to evaluate the safety and efficacy of autologous nasal septal chondroprogenitor cells. Ten participants underwent biopsy of the nasal septum cartilage during their orthognathic surgery. The harvested cells were cultured in vitro and analyzed for viability, presence of phenotype markers for mesenchymal stem and/or chondroprogenitor cells, and the potential to differentiate into chondrocytes, adipocytes, and osteoblasts. After the intra-articular injection of the cell therapy, clinical follow-up was performed using the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) and computed tomography (CT) images. No serious adverse events related to the cell therapy injection were observed during the 12-month follow-up period. It was found that autologous chondroprogenitors reduced arthralgia, promoted stabilization of mandibular function and condylar volume, and regeneration of condylar tissues. This study demonstrates that chondroprogenitor cells from the nasal septum may be a promise strategy for the treatment of temporomandibular degenerative joint disease that do not respond to other conservative therapies.

Sheltered in Stromal Tissue Cells, Trypanosoma cruzi Orchestrates Inflammatory Neovascularization via Activation of the Mast Cell Chymase Pathway.

Microangiopathy may worsen the clinical outcome of Chagas disease. Given the obstacles to investigating the dynamics of inflammation and angiogenesis in heart tissues parasitized by Trypanosoma cruzi, here we used intravital microscopy (IVM) to investigate microcirculatory alterations in the hamster cheek pouch (HCP) infected by green fluorescent protein-expressing T. cruzi (GFP-T. cruzi). IVM performed 3 days post-infection (3 dpi) consistently showed increased baseline levels of plasma extravasation. Illustrating the reciprocal benefits that microvascular leakage brings to the host-parasite relationship, these findings suggest that intracellular amastigotes, acting from inside out, stimulate angiogenesis while enhancing the delivery of plasma-borne nutrients and prosurvival factors to the infection foci. Using a computer-based analysis of images (3 dpi), we found that proangiogenic indexes were positively correlated with transcriptional levels of proinflammatory cytokines (pro-IL1ß and IFN-γ). Intracellular GFP-parasites were targeted by delaying for 24 h the oral administration of the trypanocidal drug benznidazole. A classification algorithm showed that benznidazole (>24 h) blunted angiogenesis (7 dpi) in the HCP. Unbiased proteomics (3 dpi) combined to pharmacological targeting of chymase with two inhibitors (chymostatin and TY-51469) linked T. cruzi-induced neovascularization (7 dpi) to the proangiogenic activity of chymase, a serine protease stored in secretory granules from mast cells.

Adaptive constrained constructive optimisation for complex vascularisation processes.

Mimicking angiogenetic processes in vascular territories acquires importance in the analysis of the multi-scale circulatory cascade and the coupling between blood flow and cell function. The present work extends, in several aspects, the Constrained Constructive Optimisation (CCO) algorithm to tackle complex automatic vascularisation tasks. The main extensions are based on the integration of adaptive optimisation criteria and multi-staged space-filling strategies which enhance the modelling capabilities of CCO for specific vascular architectures. Moreover, this vascular outgrowth can be performed either from scratch or from an existing network of vessels. Hence, the vascular territory is defined as a partition of vascular, avascular and carriage domains (the last one contains vessels but not terminals) allowing one to model complex vascular domains. In turn, the multi-staged space-filling approach allows one to delineate a sequence of biologically-inspired stages during the vascularisation process by exploiting different constraints, optimisation strategies and domain partitions stage by stage, improving the consistency with the architectural hierarchy observed in anatomical structures. With these features, the aDaptive CCO (DCCO) algorithm proposed here aims at improving the modelled network anatomy. The capabilities of the DCCO algorithm are assessed with a number of anatomically realistic scenarios.

Reduced-Order Unscented Kalman Filter With Observations in the Frequency Domain: Application to Computational Hemodynamics.

OBJECTIVE: The aim of this paper is to assess the potential of the reduced-order unscented Kalman's filter (ROUKF) in the context of computational hemodynamics, in order to estimate cardiovascular model parameters when employing real patient-specific data. METHODS: The approach combines an efficient blood flow solver for one-dimensional networks (for the forward problem) with the parameter estimation problem cast in the frequency space. Namely, the ROUKF is used to correct model parameters after each cardiac cycle, depending on the discrepancies of model outputs with respect to available observations properly mapped into the frequency space. RESULTS: First we validate the filter in frequency domain applying it in the context of a set of experimental measurements for an in vitro model. Second, we perform different numerical experiments aiming at parameter estimation using patient-specific data. CONCLUSION: Our results demonstrate that the filter in frequency domain allows a faster and more robust parameter estimation, when compared to its time-domain counterpart. Moreover, the proposed approach allows to estimate parameters that are not directly related to the network, but are crucial for targeting inter-individual parameter variability (e.g., parameters that characterize the cardiac output). SIGNIFICANCE: The ROUKF in frequency domain provides a robust and flexible tool for estimating parameters related to cardiovascular mathematical models using in vivo data.

An integrated mathematical model of the cardiovascular and respiratory systems.

This study presents a lumped model for the human cardiorespiratory system. Specifically, we incorporate a sophisticated gas dissociation and transport system to a fully integrated cardiovascular and pulmonary model. The model provides physiologically consistent predictions in terms of hemodynamic variables such as pressure, flow rate, gas partial pressures, and pH. We perform numerical simulations to evaluate the behavior of the partial pressures of oxygen and carbon dioxide in different vascular and pulmonary compartments. For this, we design the rest condition with low oxygen requirements and carbon dioxide production and exercise conditions with high oxygen demand and carbon dioxide production. Furthermore, model sensitivity to more relevant model parameters is studied. Copyright © 2015 John Wiley & Sons, Ltd.

Reconstrução tridimensional de artérias coronárias a partir da integração doultrassom intracoronário e da angiografia convencional / Three-dimensional reconstruction of coronary arteries based on the integration of intravascular ultrasound and conventional angiography

Introdução: A reconstrução tridimensional coronária com a combinação do ultrassom intracoronário e da angiografia apresenta vantagens em relação à angiotomografia de coronárias. Objetivamos apresentara fase piloto de validação de um novo modelo de reconstrução tridimensional de artérias coronárias. Métodos: Foram utilizados exames de angiografia e ultrassom intracoronário já realizados por indicação clínica em indivíduos com suspeita ou diagnóstico de doença arterial coronária estável. O processamento das imagens, a segmentação e a reconstrução tridimensional foram realizados seguindo metodologia específica. Para fins de caracterização geométrica, foram obtidas as linhas de centro tridimensionais. Resultados: Foram reconstruídos três vasos, sendo duas artérias descendentes anteriores e uma artéria circunflexa. O volume da luz do vaso e a carga de placa global puderam ser visualizados com facilidade com a reconstrução tridimensional. A caracterização geométrica revelou aumento dos valores absolutos do comprimento, tortuosidade, curvatura e torsão, caracterizando uma maior complexidade da linha de centro da luz doente, em relação à linha de centro da membrana elástica externa. Conclusões: Essa nova metodologia, que integrou angiografia convencional e ultrassom intracoronário, aumentou a praticidade das reconstruções, com ganho em acurácia volumétrica do vaso e visualização global de aspectos-chave da doença aterosclerótica, como remodelamento e distribuição da placa.

Background: Coronary three-dimensional reconstruction with the combination of intravascular ultrasound and angiography offers advantages over computed tomography angiography of coronary arteries. The authors aimed to present the pilot phase of the validation of a new model of three-dimensional reconstruction of coronary arteries. Methods: This study used angiography and intravascular ultrasound examinations already performed by clinical indication in individuals with known or suspected stable coronary artery disease. Image processing, segmentation, and three-dimensional reconstruction were conducted following specific methodology. For geometrical characterization purposes, tridimensional center lines were obtained. Results: Three vessels were reconstructed: two left anterior descending arteries and one left circumflex artery. The vessel lumen volume and the overall plaque burden could be easily viewed with threedimensional reconstruction. The geometric characterization revealed increased absolute values of length, tortuosity, curvature, and torsion, featuring a greater complexity of the center line of the diseased lumen relative to the center line of the external elastic membrane. Conclusions: This new methodology, which integrates conventional angiography and intravascular ultrasound, has increased the practicality of the reconstructions, with a gain in volumetric accuracy of the vessel and overall visualization of key aspects of atherosclerotic disease, such as plaque remodeling and distribution.

Free and open-source software application for the evaluation of coronary computed tomography angiography images.

BACKGROUND: The standardization of images used in Medicine in 1993 was performed using the DICOM (Digital Imaging and Communications in Medicine) standard. Several tests use this standard and it is increasingly necessary to design software applications capable of handling this type of image; however, these software applications are not usually free and open-source, and this fact hinders their adjustment to most diverse interests. OBJECTIVE: To develop and validate a free and open-source software application capable of handling DICOM coronary computed tomography angiography images. METHODS: We developed and tested the ImageLab software in the evaluation of 100 tests randomly selected from a database. We carried out 600 tests divided between two observers using ImageLab and another software sold with Philips Brilliance computed tomography appliances in the evaluation of coronary lesions and plaques around the left main coronary artery (LMCA) and the anterior descending artery (ADA). To evaluate intraobserver, interobserver and intersoftware agreements, we used simple and kappa statistics agreements. RESULTS: The agreements observed between software applications were generally classified as substantial or almost perfect in most comparisons. CONCLUSION: The ImageLab software agreed with the Philips software in the evaluation of coronary computed tomography angiography tests, especially in patients without lesions, with lesions < 50% in the LMCA and < 70% in the ADA. The agreement for lesions > 70% in the ADA was lower, but this is also observed when the anatomical reference standard is used.

Software livre e de código aberto para avaliação de imagens de angiotomografia de coronárias / Free and open-source software application for the evaluation of coronary computed tomography angiography images

FUNDAMENTO: A estandardização do padrão de imagens utilizada dentro da medicina foi realizada em 1993 por meio do padrão DICOM (Digital Imaging and Communications in Medicine). Diversos exames utilizam esse padrão e cada vez mais são necessários softwares capazes de manipular esse tipo de imagem, porém esses softwares geralmente não têm o formato livre e de código aberto, e isso dificulta o seu ajuste para os mais diferentes interesses. OBJETIVO: Desenvolver e validar um software livre e de código aberto capaz de manipular imagens DICOM de exames de angiotomografia de coronárias. MÉTODOS: Desenvolvemos e testamos o software intitulado ImageLab na avaliação de 100 exames selecionados de forma randômica por meio de um banco de dados. Foram realizadas 600 análises divididas por dois observadores utilizando o ImageLab e um outro software comercializado junto a aparelhos de tomografia computadorizada Philips Brilliance, na avaliação da presença de lesões e placas coronarianas nos territórios do Tronco da Coronária Esquerda (TCE) e na Artéria Descendente Anterior (ADA). Para avaliar as concordâncias intraobservador, interobservadores e intersoftware, utilizamos concordância simples e estatística Kappa. RESULTADOS: As concordâncias observadas entre os softwares foram em geral classificadas como substancial ou quase perfeitas na maioria das comparações. CONCLUSÃO: O software ImageLab concordou com o software Philips na avaliação de exames de angiotomografia de coronárias especialmente em pacientes sem lesões, com lesões inferiores a 50% no TCE e inferiores a 70% na ADA. A concordância para lesão >70% na ADA foi menor, porém isso também é observado quando se utiliza o padrão de referência anatômico.

BACKGROUND: The standardization of images used in Medicine in 1993 was performed using the DICOM (Digital Imaging and Communications in Medicine) standard. Several tests use this standard and it is increasingly necessary to design software applications capable of handling this type of image; however, these software applications are not usually free and open-source, and this fact hinders their adjustment to most diverse interests. OBJECTIVE: To develop and validate a free and open-source software application capable of handling DICOM coronary computed tomography angiography images. METHODS: We developed and tested the ImageLab software in the evaluation of 100 tests randomly selected from a database. We carried out 600 tests divided between two observers using ImageLab and another software sold with Philips Brilliance computed tomography appliances in the evaluation of coronary lesions and plaques around the left main coronary artery (LMCA) and the anterior descending artery (ADA). To evaluate intraobserver, interobserver and intersoftware agreements, we used simple and kappa statistics agreements. RESULTS: The agreements observed between software applications were generally classified as substantial or almost perfect in most comparisons. CONCLUSION: The ImageLab software agreed with the Philips software in the evaluation of coronary computed tomography angiography tests, especially in patients without lesions, with lesions < 50% in the LMCA and < 70% in the ADA. The agreement for lesions > 70% in the ADA was lower, but this is also observed when the anatomical reference standard is used.