Apport de l'angiographie au vert d'indocyanine (ICG) dans la localisation des néovascularisations chororoidiennes occultes [Value of indocyanine green angiography in localization of occult choroid neovascularization]

PURPOSE: To determine the role of Indocyanin Green (ICG) angiography in localizing occult new vessels associated with age-related macular degeneration (ARMD) and assess the possibilities of ICG guided laser photocoagulations. PATIENTS AND METHODS: Fluorescein and ICG angiographies (IMAGEnet system) of 62 patients with occult new vessels (ONV), serous (SPED) or vascular (VPED) pigment epithelium detachment have been studied. RESULTS: Based on fondoscopic examination and fluorescein angiography, 43 eyes (69%) disclosed ONV, 8 (13%) SPED and 11 (18%) VPED. Choroidal neovascularisation was confirmed by ICG angiography in 37 ONV cases (86%), in 8 (72%) VPED cases, but in no SPED. Conversion of ONV in classical neovascular membranes was possible in 19 ONV cases (44%) and in 6 (54%) VPED cases, making a laser photocoagulation possible in 9 eyes (36%). CONCLUSION: ICG angiography plays an important role in the evaluation, classification and laser treatment of patients with ONV secondary to ARMD.

The Macrocirculation and Microcirculation of Hypertension.

Changes in vascular structure that accompany hypertension may contribute to hypertensive end-organ damage. Both the macrovascular and microvascular levels should be considered, as interactions between them are believed to be critically important. Regarding the macrocirculation, the article first reviews basic concepts of vascular biomechanics, such as arterial compliance, arterial distensibility, and stress-strain relationships of arterial wall material, and then reviews how hypertension affects the properties of conduit arteries, particularly examining evidence that it accelerates the progressive stiffening that normally occurs with advancing age. High arterial stiffness may increase central systolic and pulse pressure by two different mechanisms: 1) Abnormally high pulse wave velocity may cause pressure waves reflected in the periphery to reach the central aorta in systole, thus augmenting systolic pressure; 2) In the elderly, the interaction of the forward pressure wave with high arterial stiffness is mostly responsible for abnormally high pulse pressure. At the microvascular level, hypertensive disease is characterized by inward eutrophic or hypertrophic arteriolar remodeling and capillary rarefaction. These abnormalities may depend in part on the abnormal transmission of highly pulsatile blood pressure into microvascular networks, especially in highly perfused organs with low vascular resistance, such as the kidney, heart, and brain, where it contributes to hypertensive end-organ damage.

Phosphorylation modulates FOXC2 transcriptional program by controlling the high-order interaction with DNA.

Phosphorylation of transcription factors is a rapid and reversible process linking cell signaling and control of gene expression, therefore understanding how it controls the transcription factor functions is one of the challenges of functional genomics. We performed such analysis for the forkhead transcription factor FOXC2 mutated in human hereditary disease lymphedemadistichiasis and important for the development of venous and lymphatic valves and lymphatic collecting vessels. We found that FOXC2 is phosphorylated in a cell-cycle dependent manner on eight evolutionary conserved serine/threonine residues, seven of which are clustered within a 70 amino acid domain. Surprisingly, the mutation of phosphorylation sites or a complete deletion of the domain did not affect the transcriptional activity of FOXC2 in a synthetic reporter assay. However, overexpression of the wild type or phosphorylation-deficient mutant resulted in overlapping but distinct gene expression profiles suggesting that binding of FOXC2 to individual sites under physiological conditions is affected by phosphorylation. To gain a direct insight into the role of FOXC2 phosphorylation, we performed comparative genome-wide location analysis (ChIP-chip) of wild type and phosphorylation-deficient FOXC2 in primary lymphatic endothelial cells. The effect of loss of phosphorylation on FOXC2 binding to genomic sites ranged from no effect to nearly complete inhibition of binding, suggesting a mechanism for how FOXC2 transcriptional program can be differentially regulated depending on FOXC2 phosphorylation status. Based on these results, we propose an extension to the enhanceosome model, where a network of genomic context-dependent DNA-protein and protein-protein interactions not only distinguishes a functional site from a nonphysiological site, but also determines whether binding to the functional site can be regulated by phosphorylation. Moreover, our results indicate that FOXC2 may have different roles in quiescent versus proliferating lymphatic endothelial cells in vivo.

Clinical role of coronary magnetic resonance angiography in the diagnosis of anomalous coronary arteries.

Though rare, anomalous coronary artery disease is a well-known cause of myocardial ischemia and sudden death among children and young adults. The projectional nature of conventional x-ray angiography often leads to difficulty in the definition of anomalous vessels. Studies have now documented the high accuracy of coronary magnetic resonance angiography (MRA) for the noninvasive detection and definition of anomalous coronary arteries among patients with suspected anomalous coronary arteries of congenital conditions associated with anomalous coronary arteries. With increasing clinical experience, coronary MRA will likely emerge as the gold standard for the diagnosis of this condition.

Combined functional and viability cardiac MR imaging in a single breathhold

The combination of cardiac viability and functional information enhances the identification of different heart tissues in the setting of ischemic heart disease. A method has recently been proposed for obtaining black-blood delayed-enhancement (DE) viability images using the stimulated-echo acquisition mode (STEAM) MRI pulse sequence in a single short breathhold. The method was validated against conventional inversion-recovery (IR) DE images for identifying regions of myocardial infarction (MI). The method was based on the acquisition of three consecutive images of the same anatomical slice. One image has T(1)-weighted contrast in which infarction appears bright. The two other images are used to construct an anatomical image of the heart, which is combined with the first image to produce a black-blood viability image. However, using appropriate modulation and demodulation frequencies, the latter two images bear useful information about myocardial deformation that results in a cardiac strain-encoding (SENC) functional image. In this work, a method is proposed for obtaining three consecutive SENC images in a single acquisition that can be combined to produce a composite image of the heart, which shows both functional and viability information. The proposed technique reduces scan time by one-half, compared with separate acquisitions of functional and viability images, and alleviates misregistration problems caused by separate breathholds.

Reproducibility of 3D free-breathing magnetic resonance coronary vessel wall imaging.

AIMS: Although the coronary artery vessel wall can be imaged non-invasively using magnetic resonance imaging (MRI), the in vivo reproducibility of wall thickness measures has not been previously investigated. Using a refined magnetization preparation scheme, we sought to assess the reproducibility of three-dimensional (3D) free-breathing black-blood coronary MRI in vivo. METHODS AND RESULTS: MRI vessel wall scans parallel to the right coronary artery (RCA) were obtained in 18 healthy individuals (age range 25-43, six women), with no known history of coronary artery disease, using a 3D dual-inversion navigator-gated black-blood spiral imaging sequence. Vessel wall scans were repeated 1 month later in eight subjects. The visible vessel wall segment and the wall thickness were quantitatively assessed using a semi-automatic tool and the intra-observer, inter-observer, and inter-scan reproducibilities were determined. The average imaged length of the RCA vessel wall was 44.5+/-7 mm. The average wall thickness was 1.6+/-0.2 mm. There was a highly significant intra-observer (r=0.97), inter-observer (r=0.94), and inter-scan (r=0.90) correlation for wall thickness (all P<0.001). There was also a significant agreement for intra-observer, inter-observer, and inter-scan measurements on Bland-Altman analysis. The intra-class correlation coefficients for intra-observer (r=0.97), inter-observer (r=0.92), and inter-scan (r=0.86) analyses were also excellent. CONCLUSION: The use of black-blood free-breathing 3D MRI in conjunction with semi-automated analysis software allows for reproducible measurements of right coronary arterial vessel-wall thickness. This technique may be well-suited for non-invasive longitudinal studies of coronary atherosclerosis.

Correction for heart rate variability during 3D whole heart MR coronary angiography.

PURPOSE: To evaluate the effect of a real-time adaptive trigger delay on image quality to correct for heart rate variability in 3D whole-heart coronary MR angiography (MRA). MATERIALS AND METHODS: Twelve healthy adults underwent 3D whole-heart coronary MRA with and without the use of an adaptive trigger delay. The moment of minimal coronary artery motion was visually determined on a high temporal resolution MRI. Throughout the scan performed without adaptive trigger delay, trigger delay was kept constant, whereas during the scan performed with adaptive trigger delay, trigger delay was continuously updated after each RR-interval using physiological modeling. Signal-to-noise, contrast-to-noise, vessel length, vessel sharpness, and subjective image quality were compared in a blinded manner. RESULTS: Vessel sharpness improved significantly for the middle segment of the right coronary artery (RCA) with the use of the adaptive trigger delay (52.3 +/- 7.1% versus 48.9 +/- 7.9%, P = 0.026). Subjective image quality was significantly better in the middle segments of the RCA and left anterior descending artery (LAD) when the scan was performed with adaptive trigger delay compared to constant trigger delay. CONCLUSION: Our results demonstrate that the use of an adaptive trigger delay to correct for heart rate variability improves image quality mainly in the middle segments of the RCA and LAD.

Postmortem whole-body CT angiography: evaluation of two contrast media solutions.

OBJECTIVE: The objective of our study was to establish a standardized procedure for postmortem whole-body CT-based angiography with lipophilic and hydrophilic contrast media solutions and to compare the results of these two methods. MATERIALS AND METHODS: Minimally invasive postmortem CT angiography was performed on 10 human cadavers via access to the femoral blood vessels. Separate perfusion of the arterial and venous systems was established with a modified heart-lung machine using a mixture of an oily contrast medium and paraffin (five cases) and a mixture of a water-soluble contrast medium with polyethylene glycol (PEG) 200 in the other five cases. Imaging was executed with an MDCT scanner. RESULTS: The minimally invasive femoral approach to the vascular system provided a good depiction of lesions of the complete vascular system down to the level of the small supplying vessels. Because of the enhancement of well-vascularized tissues, angiography with the PEG-mixed contrast medium allowed the detection of tissue lesions and the depiction of vascular abnormalities such as pulmonary embolisms or ruptures of the vessel wall. CONCLUSION: The angiographic method with a water-soluble contrast medium and PEG as a contrast-agent dissolver showed a clearly superior quality due to the lack of extravasation through the gastrointestinal vascular bed and the enhancement of soft tissues (cerebral cortex, myocardium, and parenchymal abdominal organs). The diagnostic possibilities of these findings in cases of antemortem ischemia of these tissues are not yet fully understood.

Plaque characteristics and arterial remodeling in coronary and peripheral arterial systems.

BACKGROUND: Few studies have examined plaque characteristics among multiple arterial beds in vivo. The purpose of this study was to compare the plaque morphology and arterial remodeling between coronary and peripheral arteries using gray-scale and radiofrequency intravascular ultrasound (IVUS) at clinical presentation. METHODS AND RESULTS: IVUS imaging was performed in 68 patients with coronary and 93 with peripheral artery lesions (29 carotid, 50 renal, and 14 iliac arteries). Plaques were classified as fibroatheroma (VH-FA) (further subclassified as thin-capped [VH-TCFA] and thick-capped [VH-ThCFA]), fibrocalcific plaque (VH-FC) and pathological intimal thickening (VH-PIT). Plaque rupture (13% of coronary, 7% of carotid, 6% of renal, and 7% of iliac arteries; P = NS) and VH-TCFA (37% of coronary, 24% of carotid, 16% of renal, and 7% of iliac arteries; P = 0.02) were observed in all arteries. Compared with coronary arteries, VH-FA was less frequently observed in renal (P < 0.001) and iliac arteries (P < 0.006). Lesions with positive remodeling demonstrated more characteristics of VH-FA in coronary (84% vs. 25%, P < 0.001), carotid (72% vs. 20%, P = 0.001), and renal arteries (42% vs. 4%, P = 0.001) compared with those with intermediate/negative remodeling. There was positive relationship between remodeling index and percent necrotic area in all four arteries. CONCLUSIONS: Atherosclerotic plaque phenotypes were heterogeneous among four different arteries; renal and iliac arteries had more stable phenotypes compared with coronary artery. In contrast, the associations of remodeling pattern with plaque phenotype and composition were similar among the various arterial beds.

Leukocyte-endothelial cell interaction is necessary for photodynamic therapy induced vascular permeabilization.

BACKGROUND AND OBJECTIVE: Photodynamic therapy (PDT) affects vascular barrier function and thus increases vessel permeability. This phenomenon may be exploited to facilitate targeted drug delivery and may lead to a new clinical application of photodynamic therapy. Here, we investigate the role of leukocyte recruitment for PDT-induced vascular permeabilization. STUDY DESIGN/MATERIAL AND METHODS: Fluorescein isothiocyanate dextran (FITC-D, 2,000 kDa) was injected intravenously 120 minutes after focal PDT on striated muscle in nude mice bearing dorsal skinfold chambers (Visudyne® 800 µg/kg, fluence rate 300 mW/cm2 , light dose of 200 J/cm2). Leukocyte interaction with endothelial cells was inhibited by antibodies functionally blocking adhesion molecules ("MABS-PDT" group, n = 5); control animals had PDT but no antibody injection (group "PDT", n = 7). By intravital microscopy, we monitored leukocyte rolling and sticking in real-time before, 90 and 180 minutes after PDT. The extravasation of FITC-D from striated muscle vessels into the interstitial space was determined in vivo during 45 minutes to assess treatment-induced alterations of vascular permeability. RESULTS: PDT significantly increased the recruitment of leukocytes and enhanced the leakage of FITC-D. Neutralization of adhesion molecules before PDT suppressed the rolling of leukocytes along the venular endothelium and significantly reduced the extravasation of FITC-D as compared to control animals (156 ± 27 vs. 11 ± 2 (mean ± SEM, number of WBC/30 seconds mm vessel circumference; P < 0.05) at 90 minutes after PDT and 194 ± 21 vs. 14 ± 4 at 180 minutes after PDT). In contrast, leukocyte sticking was not downregulated by the antibody treatment. CONCLUSION: Leukocyte recruitment plays an essential role in the permeability-enhancing effect of PDT.

The PPARgamma agonist pioglitazone modifies the vascular sodium-angiotensin II relationship in insulin-resistant rats.

Glitazones are efficient insulin sensitizers that blunt the effects of angiotensin II (ANG II) in the rat. Sodium chloride is another important modulator of the systemic and renal effects of ANG II. Whether glitazones interfere with the interaction between sodium and the response to ANG II is not known. Therefore, we investigated the effects of pioglitazone on the relationship between sodium and the systemic and renal effects of ANG II in rats. Pioglitazone, or vehicle, was administered for 4 wk to 8-wk-old obese Zucker rats. Animals were fed a normal-sodium (NS) or a high-sodium (HS) diet. Intravenous glucose tolerance tests, systemic and renal hemodynamic responses to ANG II, and the renal ANG II binding and expression of ANG II type 1 (AT(1)) receptors were measured. The results of our study were that food intake and body weight increased, whereas blood pressure, heart rate, filtration fraction, and insulin levels decreased significantly with pioglitazone in obese rats on both diets. Pioglitazone blunted the systemic response to ANG II and abolished the increased responsiveness to ANG II induced by a HS diet. Pioglitazone modified the renal hemodynamic response to changes in salt intake while maintaining a lower filtration fraction with ANG II perfusion. These effects were associated with a decrease in the number and expression of the AT(1) receptor in the kidney. In conclusion, these data demonstrate that the peroxisome proliferator-activated receptor-gamma agonist pioglitazone modifies the physiological relationship between sodium chloride and the response to ANG II in insulin-resistant rats.

Survival and health in liveborn infants with transposition of great arteries--a population-based study.

OBJECTIVE: To describe treatment, survival, and morbidity for liveborn infants with isolated transposition of great arteries (TGA). DESIGN: Population-based data from 7 European registries of congenital malformations (EUROCAT). RESULTS: Ninety-seven infants were diagnosed with isolated TGA and livebirth prevalence was 2.0 per 10,000 livebirths. The majority of infants were treated with prostaglandins (83%) and 57% had a catheter atrial septostomia performed. Arterial switch surgery was performed in 78 infants, other or unknown type of surgery was performed in 3 cases, and for 6 infants there was no information on surgery. At 1 year of age 69 infants were alive (71%) and 24 (25%) were dead (4 unknown). There were 10 deaths before surgery and 58% of all deaths took place during the first week. There was no statistically significant regional difference in mortality. Eight infants diagnosed prenatally all survived to 1 year and only 71% of infants diagnosed after birth survived (P = 0.08). Data on morbidity at 1 year of age was available for 57 infants. Fifty-one infants were reported with normal health and development. CONCLUSIONS: In this population-based study survival for liveborn infants with TGA is lower than in studies published from tertiary centers. Outcome for survivors at 1 year of age seems favorable.

Coronary artery imaging by magnetic resonance.

Non-invasive visualization of the coronary arteries represents a major challenge in modern cardiology, but this goal may be achieved in the near future by MR angiography. Possible applications are non-invasive diagnosis of coronary artery disease, and follow-up examinations for therapy control after PTCA, in order to detect restenosis at an early stage. A multiple slice technique (2 mm slice thickness, with a spatial resolution of 1 x 1 mm, Philips Gyroscan ACS-II, 1.5 Tesla) was used. Ten volunteers were imaged and 10 patients with coronary artery disease were examined before and after PTCA. MR measurements were validated by quantitative coronary angiography. The diameters of the proximal coronary arteries as measured by both methods were compared, and a good correlation was found (r = 0.76). Thus, it is concluded that non-invasive visualization of the coronary arteries is possible before and after PTCA and allows to determine potential restenoses. However, patient cooperation is essential for good image quality. Moreover, limited spatial image resolution and breathing artifacts restrict MR coronary angiography today to be used as a routine diagnostic tool for the diagnosis of coronary artery disease.

Interstitial dendritic cell guidance by haptotactic chemokine gradients.

Directional guidance of cells via gradients of chemokines is considered crucial for embryonic development, cancer dissemination, and immune responses. Nevertheless, the concept still lacks direct experimental confirmation in vivo. Here, we identify endogenous gradients of the chemokine CCL21 within mouse skin and show that they guide dendritic cells toward lymphatic vessels. Quantitative imaging reveals depots of CCL21 within lymphatic endothelial cells and steeply decaying gradients within the perilymphatic interstitium. These gradients match the migratory patterns of the dendritic cells, which directionally approach vessels from a distance of up to 90-micrometers. Interstitial CCL21 is immobilized to heparan sulfates, and its experimental delocalization or swamping the endogenous gradients abolishes directed migration. These findings functionally establish the concept of haptotaxis, directed migration along immobilized gradients, in tissues.