Detection Of Neovascularization Research Articles

Efeito da suplementação dietética de arginina na cicatrização das anastomoses colônicas em ratos

RACIONAL: A arginina, aminoácido condicionalmente essencial, participa de diversos processos fisiológicos, em particular na cicatrização e na função imune. OBJETIVO: Avaliar o efeito da suplementação por via oral da arginina na cicatrização colônica em ratos. MÉTODO: Foram utilizados 47 ratos Wistar machos, adultos, com peso médio de 345,45 ± 8,35g, alocados em gaiolas coletivas em grupos cinco ou seis animais. Todos receberam água e ração ad libitum, pesados a cada dois dias e randomizados para receberem por gavagem suplementação com arginina a 10% (grupo ARG) ou solução de aminoácidos a 10% (grupo AA) de forma isovolumétrica, isocalórica e isonitrogenada (1,5 g/kg/dia) por sete dias antes do procedimento operatório e quatro após. Um terceiro grupo recebeu solução salina isotônica (grupo SSI), isovolumetricamente. Os ratos foram submetidos a duas colônicas término-terminais confeccionadas 3 cm distais à válvula ileocecal e outra 5 cm distais à primeira, em plano único com fio monofilamentar de nylon 5-0, e foram sacrificados no 5º dia de pós-operatório Neste dia, as duas anastomoses foram ressecadas, sendo uma conservada em solução salina para medidas de tração e a outra enviada à anatomia patológica, para análise do colágeno (total, maduro e imaturo), e imunoistoquímica para a pesquisa de miofibroblastos e neovascularização. Foi avaliado o peso corpóreo ao longo do experimento. A análise estatística foi realizada com os testes t de Student e de Mann-Whitney. RESULTADOS: A comparação referente ao peso nos três grupos não evidenciou diferença significativa nos pesos iniciais, mas foi observada diferença entre os finais nos grupos SSI e AA (324,7g vs. 298g, P=0,04). A tensão foi significativamente maior no grupo AA quando comparado ao grupo SSI (0,94kgf/cm² vs 0,67 kgf/cm², P=0,04), mas não em relação ao grupo ARG (0,94kgf/cm² vs 0,70 kgf/cm², P=0,09). Quanto à força máxima de tração observou-se diferença significativa entre o grupo AA e o grupo SSI (0,18kgf vs 0,13 kgf, P=0,04) mas não em relação ao grupo ARG (0,18kgf vs 0,14 kgf, P=0,08). A força de ruptura total evidenciou valor significativamente maior para o grupo AA quando comparado ao grupo ARG (0,10kgf vs 0,06 kgf, P=0,05), mas não em relação ao grupo SSI (0,10kgf vs 0,09 kgf, P=0,54). Não foi observada diferença significativa quanto à concentração dos colágenos subtipo I e III e nem do índice de maturação de colágeno nos três grupos. Não foi observada também diferença significativa em relação à contagem de vasos sanguíneos ou miofibroblastos pela imunoistoquímica entre os três grupos. CONCLUSÃO: A administração de solução contendo 20 aminoácidos se mostrou mais efetiva do que a administração isolada de arginina nas provas de tração das anastomoses colônicas.

Color Doppler sonography and angioscintigraphy in hepatic Hodgkin’s lymphoma

To estimate the characteristics of Color Doppler findings and the results of hepatic radionuclide angiography (HRA) in secondary Hodgkin's hepatic lymphoma. The research included patients with a diagnosis of Hodgkin's lymphoma with metastatic focal lesions in the liver and controls. Morphologic characteristics of focal liver lesions and hemodynamic parameters were examined by pulsed and Color Doppler in the portal, hepatic and splenic veins were examined. Hepatic perfusion index (HPI) estimated by HRA was calculated. In the majority of patients, hepatomegaly was observed. Lesions were mostly hypoechoic and mixed, solitary or multiple. Some of the patients presented with dilated splenic veins and hepatofugal blood flow. A pulse wave was registered in the centre and at the margins of lymphoma. The average velocity of the pulse wave was higher at the margins (P > 0.05). A continuous venous wave was found only at the margins of lymphoma. There was no linear correlation between lymphoma size and velocity of pulse and continuous wave (r = 390, P < 0.01). HPI was significantly lower in patients with lymphomas than in controls (P < 0.05), pointing out increased arterial perfusion in comparison to portal perfusion. Color Doppler ultrasonography is a sensitive method for the detection of neovascularization in Hodgkin's hepatic lymphoma and estimation of its intensity. Hepatic radionuclide angiography can additionally help in the assessment of vascularisation of liver lesions.

Imaging of the vasa vasorum

Neovascularization of the arterial walls by adventitial vasa vasorum appears to participate in the process of atherosclerosis progression and destabilization. Although the biological mechanisms associated with plaque instability are still unclear, the uncontrolled formation of intraplaque neovessels appears to contribute to the development of complex atheromatous lesions. Recent reports have described the use of several ultrasound-based techniques for the real-time detection of intraplaque neovascularization. Preliminary studies in animal models have shown that the detection and characterization of adventitial neovascularization are technically feasible. The further development of these imaging techniques relies on the successful implementation of contrast microspheres capable of enhancing microvascular structures. These contrast agents serve as surrogate red blood cells and perform acoustically as true intravascular tracers providing, in real-time, the amount and distribution of neovessels within atherosclerotic lesions. Several ultrasound-based techniques are under development for the detection of adventitial vasa vasorum in the carotid and coronary vascular territories. Although still in early validation phases, these techniques might permit the early diagnosis and stratification of subclinical atherosclerosis, thus permitting aggressive preventive therapy. In the near future, innovative contrast agents using specific ligands are likely to expand the diagnostic and therapeutic possibilities of these emerging imaging techniques.

Contrast-enhanced ultrasound imaging of atherosclerotic carotid plaque neovascularization: a new surrogate marker of atherosclerosis?

An atherosclerotic plaque requires a nutrient blood supply, which is predominantly derived from arterial vasa vasorum. A variety of factors (environmental and genetic) contribute to the initiation and growth of atherosclerosis within vessel walls. Chemotactic factors, such as tissue ischemic and hypoxic factors, stimulate the release of vascular endothelial growth factor (VEGF) proteins, resulting in vessel wall angiogenesis. These developments often precede the formation of the luminal plaque. In this report, we describe the use of contrast-enhanced carotid ultrasound (CECU) imaging for the detection and quantification of intra-plaque neovascularization. The efficacy of CECU was measured against the neovascular density observed within the tissue specimens obtained at the time of carotid endarterectomy surgery. The objective of this study was to provide a histologic correlation between CECU and carotid artery atherosclerotic plaque neovascularization. Fifteen patients with significant atherosclerotic carotid artery disease received a CECU examination prior to undergoing a carotid endarterectomy (CEA). Two patients received bilateral endarterectomies, resulting in a total of 17 cases. At the time of surgery, carotid plaque samples were surgically removed and stained with specific vascular markers (CD31, CD34, von Willebrand factor, and hemosiderin) designed to identify the presence and degree of neovascularization. The intra-plaque neovascularization recorded on preoperative CECU was correlated with the degree of neovascularization noted in the tissue specimens. The CECU neovascularization was correlated to CD31-stained tissue specimens. This correlation value was 0.68 using Spearman's rank method. When CECU results were correlated with the other histologic markers (CD34, von Willebrand factor, and hemosiderin), a correlation of 0.50 was obtained. In conclusion, contrast-enhanced carotid ultrasound correlated to the presence and degree of intra-plaque neovascularization as determined from histology specimens.

Imagerie des mélanomes : performances de l’échographie sans et avec injection de produit de contraste pour le diagnostic et l’évaluation des traitements

INTEREST FOR DIAGNOSIS: High-frequency sonography (12-16 MHz) allows to visualize primary cutaneous melanomas. The maximal echographic thickness was measured and strongly correlated to the Breslow index (p< 10(-4)). Lesions were well defined with homogeneous hypoechoic echostructure. A study including 111 patients with a 5 years median follow-up period demonstrated that the detection of neo-vascularization by color Doppler was significantly correlated to occurrence of metastasis (p < 10(-4)). INTEREST FOR EARLY EVALUATION OF TREATMENTS: For patients with local recurrent melanomas treated by isolated limb perfusion, contrast enhanced ultrasonography allows early evaluation of therapeutic. The access to raw linear data associated to quantification software permits to estimate tumoral perfusion. Several perfusion parameters (area under the contrast tune intensity curve, maximal intensity peak, mean transit time,...) are obtained after curves modelization. A study of 40 patients with a follow-up by dynamic contrast enhanced ultrasonography at D-1, D+1, D+7 and D+30 demonstrated that means of the quantification using raw linear data was able to identify as early as D+1 patients with complete response at 3 months.

Current events about echography in 2006: position of the ultrasound functional imaging for the early evaluation of targeted therapeutics

The early and functional evaluation of new treatments in oncology is a main goal. At present, technical advances in Doppler ultrasonography allow the detection of neovascularization for superficial and deep malignant tumours in order to evaluate the efficiency of new treatments such as antiangiogenic molecules. Contrast agents injection improves the efficiency of this technique and developments of perfusion softwares optimize this detection. Slow flows in tumour microvessels can be detected. Treatment response can be early predicted based on changes in the vascularization before volume modification. The availability of quantification softwares operating from the raw data before their compression for video display affords one and objective quantification of the contrast agent uptake.

Évaluation fonctionnelle et précoce des traitements en cancérologie : intérêt des produits de contraste ultrasonores

The early and functional evaluation of new treatments in oncology is a main goal. At present, technical advances in Doppler-ultrasonography allow the detection of neovascularization for superficial and deep malignant tumors in order to evaluate the efficiency of new treatments asas: 1) antiangiogenic molecules (Néovastat, Sugen, TNFα…); 2) physical destruction of vascularization in hepatic lesions by radio-frequency. Slow flows in tumoral microvessels can be detected. Treatment response can be early predicted according to modifications of this vascularization before volume modification. Contrast agents injection improves the efficiency of this technique and developments in perfusion softwares optimize this detection.

Investigation of Laser-Induced Choroidal Neovascularization in the Rat

Choroidal neovascularization plays an important role in pathogenesis of age-related macular degeneration. Induction of neovascularization by laser photocoagulation in the rat fundus is an established animal model in which the effects of new therapeutic approaches are assessed. The purpose of this study was to compare different detection methods of laser-induced neovascularization in the rat. Laser spots were applied to the fundus of Long-Evans rats. Ten days after, four different methods were used to detect laser-induced neovascularization: (1) high-resolution angiography with fluorescein isothiocyanate-dextran, (2) immunohistochemical visualization of platelet endothelial cell adhesion molecule (PECAM)-1, (3) visualization of intravascular lumens by peroxidase perfusion in the living rat with subsequent histologic analysis, and (4) histochemical representation of alkaline phosphatase in endothelial cells. At the rim of the laser scars vessel-forming endothelial cells with intravasal dextran and peroxidase were present. Cross-sections demonstrated that these vessels originated from the retina. The center of the scars contained homogenous endothelial cells of choroidal origin, which was confirmed by immunohistochemistry and electron microscopy. In laser-treated eyes without FITC-dextran perfusion, scars showed unspecific fluorescence, making differentiation from specific FITC-dextran-associated fluorescence difficult. In the rat model of laser-induced neovascularization, newly developed endothelial cells originate from the retina and the choroid. Whereas ring-like surrounding vessels come from the retina, flat endothelial cells in deeper layers are of choroidal origin or may originate from circulating endothelial precursor cells. Dextran angiography has to be regarded critically for visualizing the choriocapillaris and CNV in laser scars. PECAM-1 immunohistochemistry is best for detection and quantification of neovascularization in laser scars.

Nordic research in ophthalmology.

To provide an overview of some of the current activities in eye research in the Nordic countries. The presentations at the biannual Nordic Congress of Ophthalmology, held in Tampere, Finland in 2002, were reviewed and the contributions found most noteworthy are included in this article along with a limited discussion of each research field. However, space requirements prevented the inclusion of many interesting scientific contributions. Important contributions in various subfields of eye research and ophthalmology are reviewed. These include cornea, cataract, paediatric ophthalmology, glaucoma, diabetic eye disease, age-related macular degeneration, physiology and pharmacology and oncology. Eye research is very active in the Nordic countries and significant contributions are being made to ophthalmology in several fields on a world scale. We hope to continue to review Nordic contributions to eye research after each Nordic Congress of Ophthalmology and plan to make the reviews more systematic and comprehensive in the future.

Retinal ischemia and angle neovascularization in proliferative diabetic retinopathy

PURPOSE: To analyze the relationship between the extent of retinal ischemia in proliferative diabetic retinopathy and angle neovascularization. METHODS: Panoramic fundus fluorescein angiography and 360-degree fluorescein gonioangiography to detect the angle neovascularization were performed on 70 eyes of 46 patients with proliferative diabetic retinopathy. Statistical significance was evaluated by chi-squared test. Statistical significance was evaluated if the value (T) was greater than the level of significance, χ 0.05 2(2) = 5.99. RESULTS: Retinal ischemia in fluorescein angiography was evaluated in four areas: capillary occlusion in (1) temporal raphe; (2) radial peripapillary capillaries; (3) the midperiphery (grade I, less than 25% of the area; grade II, 25% to 50%; grade III, 50% to 75%; grade IV, more than 75%); and (4) optic disk with neovascularization. The angle neovascularization was divided into two types: type I (14 eyes) and type II (12 eyes). Capillary occlusion in the temporal raphe and radial peripapillary capillaries, and papillary leakage significantly increased the risk of angle neovascularization (T = 8.28, 10.04, 6.44 respectively). Grade III and IV capillary occlusion in the midperiphery had a significant risk of angle neovascularization when compared with grade I (between grade III: T = 9.03, grade IV: T = 19.36) and II (between grade III: T = 6.31, grade IV: T = 16.09). CONCLUSION: Risk factors for angle neovascularization were retinal nonperfusion in the midperiphery wider than grade III, capillary occlusion in the radial peripapillary capillaries and temporal raphe, and optic disk. Fluorescein gonio angiography was found to be a powerful tool for the early detection of angle neovascularization, especially in dark irides.

Evaluating persistent and recurrent choroidal neovascularization: The role of indocyanine green angiography

Objective To evaluate the clinical utility of routinely using indocyanine green angiography (ICGA) with fluorescein angiography (FA) in detecting persistent or recurrent choroidal neovascularization (CNV). Design Prospective, consecutive case series. Participants Twenty-four eyes of 21 patients with exudative age-related macular degeneration (AMD) that had conventional laser treatment for CNV were examined. Intervention Fluorescein angiography and ICGA were performed together on all eligible eyes at the first post-treatment visit and all subsequent follow-up visits in which persistent or recurrent CNV was suspected clinically. Main outcome measures Choroidal neovascularization detection and delineation by each angiographic technique were measured. Results Of the 54 FA-ICGA study pairs performed over a 20-month investigation period, FA showed well-defined, ill-defined, and no CNV in 10 (19%), 19 (35%), and 25 (46%) eyes, respectively. Indocyanine green angiography had a high concordance rate at 70% and 88% when persistent or recurrent CNV was well-defined and absent, respectively, on FA and rarely added additional, clinically useful information in these settings, particularly in the former presentation. Of the 29 eyes that showed some evidence of CNV by FA, the neovascular complex was ill-defined in 19 (66%) eyes. When CNV was ill-defined by FA, the corresponding ICGA showed well-defined CNV in 9 (47%) of 19 eyes, in 5 of which the CNV was nonsubfoveal in location. Conclusions Persistent or recurrent CNV in AMD was frequently ill-defined by FA. Indocyanine green angiography was a valuable adjunct to FA by better delineating CNV in this specific setting. However, ICGA was not useful when the post-treatment FA showed well-defined CNV. Furthermore, ICGA was not helpful when the first post-treatment FA was negative and there were no ophthalmoscopic signs of exudation.

20 Use of the functional imaging modalities, f MRI r CBV and PET FDG, alters radiation therapy 3-D treatment planning in patients with malignant gliomas

Malignant gliomas present one of the most difficult challenges to definitive radiation therapy, not only with respect to local control, but also with respect to clinical functional status. While tumor target volume definitions for malignant gliomas are often based on CT and conventional MRI, the functional imaging modalities, echo planar rCBV (regional cerebral blood volume mapping) and 18F-fluorodeoxyglucose PET, are more sensitive modalities for the detection of neovascularization, perhaps one of the earliest signs of glial tumor initiation and progression. In order to address the clinical utility of functional imaging in radiation therapy 3-D treatment planning, we compared tumor target volume definitions and overall dosimetry in patients either undergoing co-registration of conventional Gadolinium-enhanced MRI, or co-registration of functional imaging modalities, prior to radiation therapy 3-D treatment planning.

Early Detection of Extrafoveal Neovascular Membranes by Daily Central Field Evaluation

Argon laser photocoagulation can reduce the risk of severe vision loss in patients with age-related macular degeneration, ocular histoplasmosis, and idiopathic neovascularization. Early detection of neovascularization soon after the onset increases the likelihood of identifying patients with a new vessel membrane in a potentially treatable position. Patients with one or both eyes at risk for the development of a new vessel membrane should assess their central visual fields on a daily basis by occluding first one eye and then the other. Any disturbance in distance vision or reading vision or the appearance of distortion in the patient's field or on the Amsler grid should prompt an eye examination at the earliest feasible time, in an effort to detect neovascularization in a treatable position.