RESUMO
Atherosclerotic plaques are complex tissues containing many different cell types. Macrophages contribute to inflammation, formation of the necrotic core, and plaque rupture. We examined whether macrophages in plaque can be activated and compared this to monolayer cells. The volume of calcium in the plaque was compared to the level of macrophage activation measured by total neopterin output. Carotid plaque samples were cut into 3â¯mm sections and cultured for up to 96â¯h. Live sections were stimulated with interferon-γ, phytohaemagglutinin or phorbol 12-myristate 13-acetate. Macrophage activation and oxidative stress were monitored by total neopterin (oxidized and non-oxidized 7,8-dihydroneopterin) and neopterin levels every 24â¯h for up to 4â¯d. The calcium content of two plaques was investigated by spectral imaging. Direct stimulation of macrophages in plaque sections with interferon-γ caused a sustained increase in neopterin (pâ¯=â¯.037) and total neopterin (pâ¯=â¯.003). The addition of phorbol 12-myristate 13-acetate to plaque had no significant effect on total neopterin production (pâ¯=â¯.073) but increased neopterin (pâ¯=â¯.037) whereas phytohaemagglutinin caused a significant increase in both neopterin and total neopterin (pâ¯=â¯.0279 and .0168). There was an inverse association (R2â¯=â¯0.91) between the volume of calcium and macrophage activation as measured by total neopterin production in stimulated plaque tissue. Resident macrophages within excised carotid plaque activated either directly or indirectly generate the biomarkers 7,8-dihydroneopterin and neopterin. Macrophage activation rather than the oxidative environment is associated with plaque calcification.
Assuntos
Cálcio/imunologia , Macrófagos/imunologia , Estresse Oxidativo/imunologia , Placa Aterosclerótica/imunologia , Feminino , Humanos , Interferon gama/farmacologia , Ativação de Macrófagos , Macrófagos/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Fito-Hemaglutininas/farmacologia , Placa Aterosclerótica/patologia , Acetato de Tetradecanoilforbol/farmacologiaRESUMO
In this paper, we present a method that uses a combination of experimental and modeled data to assess properties of x-ray beam measured using a small-animal spectral scanner. The spatial properties of the beam profile are characterized by beam profile shape, the angular offset along the rotational axis, and the photon count difference between experimental and modeled data at the central beam axis. Temporal stability of the beam profile is assessed by measuring intra- and interscan count variations. The beam profile assessment method was evaluated on several spectral CT scanners equipped with Medipix3RX-based detectors. On a well-calibrated spectral CT scanner, we measured an integral count error of 0.5%, intrascan count variation of 0.1%, and an interscan count variation of less than 1%. The angular offset of the beam center ranged from 0.8° to 1.6° for the studied spectral CT scanners. We also demonstrate the capability of this method to identify poor performance of the system through analyzing the deviation of the experimental beam profile from the model. This technique can, therefore, aid in monitoring the system performance to obtain a robust spectral CT; providing the reliable quantitative images. Furthermore, the accurate offset parameters of a spectral scanner provided by this method allow us to incorporate a more realistic form of the photon distribution in the polychromatic-based image reconstruction models. Both improvements of the reliability of the system and accuracy of the volume reconstruction result in a better discrimination and quantification of the imaged materials.