Relation between plaque type, plaque thickness, blood shear stress, and plaque stress in coronary arteries assessed by X-ray Angiography and Intravascular Ultrasound

Purpose: Atheromatic plaque progression is affected, among others phenomena, by biomechanical, biochemical, and physiological factors. In this paper, the authors introduce a novel framework able to provide both morphological (vessel radius, plaque thickness, and type) and biomechanical (wall shear stress and Von Mises stress) indices of coronary arteries. Methods: First, the approach reconstructs the three-dimensional morphology of the vessel from intravascular ultrasound(IVUS) and Angiographic sequences, requiring minimal user interaction. Then, a computational pipeline allows to automatically assess fluid-dynamic and mechanical indices. Ten coronary arteries are analyzed illustrating the capabilities of the tool and confirming previous technical and clinical observations. Results: The relations between the arterial indices obtained by IVUS measurement and simulations have been quantitatively analyzed along the whole surface of the artery, extending the analysis of the coronary arteries shown in previous state of the art studies. Additionally, for the first time in the literature, the framework allows the computation of the membrane stresses using a simplified mechanical model of the arterial wall. Conclusions: Circumferentially (within a given frame), statistical analysis shows an inverse relation between the wall shear stress and the plaque thickness. At the global level (comparing a frame within the entire vessel), it is observed that heavy plaque accumulations are in general calcified and are located in the areas of the vessel having high wall shear stress. Finally, in their experiments the inverse proportionality between fluid and structural stresses is observed.

Anatomy of liver arteries for interventional radiology.

The availability of intra-arterial hepatic therapies (radio and/or chemo-embolisation, intra-arterial hepatic chemotherapy) has convinced radiologists to perfect their knowledge of the anatomy of the liver arteries. These sometimes, complex procedures most often require selective arterial catheterization. Knowledge of the different arteries in the liver and the peripheral organs is therefore essential to optimize the procedure and avoid eventual complications. This paper aims to describe the anatomy of the liver arteries and the variants, applying it to angiography images, and to understand the implications of such variations in interventional radiological procedures.

Assessment of intima-media complex in carotid, femoral and right subclavian arteries for early investigation of atherosclerosis in HIV-infected patients

Objective To compare automatic and manual measurements of intima-media complex (IMC) in common carotid, common femoral and right subclavian arteries of HIV-infected patients in relation to a control group, taking into consideration the classical risk factors for atherosclerosis. Materials and Methods The study sample comprised 70 HIV-infected patients and 70 non-HIV-infected controls paired according sex and age. Automatic (gold standard) and manual measurements of IMC were performed in the carotid arteries. Manual measurements were also performed in common femoral and right subclavian arteries. Bland-Altman graphs were utilized in the comparison and the adopted level significance was 5%. Results Intima-media complex alterations were not observed in any of the individuals as the mean automatic measurement in the right common carotid (RCC) artery was considered as the gold standard. As the gold standard was compared with the manual measurements (mean, maximum and minimum), no clinically significant alteration was observed. As the gold standard was compared with other sites, the difference was statistically and clinically significant at the origin of right subclavian artery (RCC: 0.51 mm vs. 0.91 mm) (p < 0.001). Conclusion HIV-infected individuals are not at higher risk for atherosclerosis than the control population.

Regulating Mechanisms of Gonadal and Pituitary Tumorigenesis in Mice Producing Human Chorionic Gonadotropin

Human chorionic gonadotropin (hCG) and luteinizing hormone (LH) are structurally and functionally similar glycoprotein hormones acting through the same luteinizing hormone chorionic gonadotropin receptor (LHCGR). The functions of LH in reproduction and hCG in pregnancy are well known. Recently, the expression of LHCGR has been found in many nongonadal tissues and cancers, and this has raised the question of whether LH/hCG could affect the function or tumorigenesis of these nongonadal tissues. We have also previously generated an hCG expressing mouse model presenting nongonadal phenotypes. Using this model it is possible to improve our understanding of nongonadal action of highly elevated LH/hCG. In the current study, we analyzed the effect of moderately and highly elevated hCG levels on male reproductive development and function. The main finding was the appearance of fetal Leydig cell (FLC) adenomas in prepubertal males. However, the development and differentiation of FLCs were not significantly affected. We also show that the function of hCG is different in FLCs and in adult Leydig cells (ALC), because in the latter cells hCG was not able to induce tumorigenesis. In FLCs, LHCGR is not desensitized or downregulated upon ligand binding. In this study, we found that the testicular expression of two G protein-coupled receptor kinases responsible for receptor desensitization or downregulation is increased in adult testis. Results suggest that the lack of LHCGR desensitization or downregulation in FLCs protect testosterone (Te) synthesis, but also predispose FLCs for LH/hCG induced adenomas. However, all the hCG induced nongonadal changes observed in male mice were possible to explain by the elevated Te level found in these males. Our findings indicate that the direct nongonadal effects of elevated LH/hCG in males are not pathophysiologically significant. In female mice, we showed that an elevated hCG level was able to induce gonadal tumorigenesis. hCG also induced the formation of pituitary adenomas (PA), but the mechanism was indirect. Furthermore, we found two new potential risk factors and a novel hormonally induced mechanism for PAs. Increased progesterone (P) levels in the presence of physiological estradiol (E2) levels induced the formation of PAs in female mice. E2 and P induced the expression and nuclear localization of a known cell-cycle regulator, cyclin D1. A calorie restricted diet was also able to prevent the formation of PAs, suggesting that obesity is able to promote the formation of PAs. Hormone replacement therapy after gonadectomy and hormone antagonist therapy showed that the nongonadal phenotypes observed in hCG expressing female mice were due to ovarian hyperstimulation. A slight adrenal phenotype was evident even after gonadectomy in hCG expressing females, but E2 and P replacement was able to induce a similar phenotype in WT females without elevated LH/hCG action. In conclusion, we showed that the direct effects of elevated hCG/LH action are limited only to the gonads of both sexes. The nongonadal phenotypes observed in hCG expressing mice were due to the indirect, gonadal hormone mediated effects of elevated hCG. Therefore, the gonads are the only physiologically significant direct targets of LHCGR signalling.

Uterine Doppler velocimetry of the uterine arteries in the second and third trimesters for the prediction of gestational outcome

PURPOSE: The aim of this longitudinal study was to investigate the value of uterine artery Doppler sonography during the second and third trimesters in the prediction of adverse pregnancy outcome in low-risk women. METHODS: From July 2011 to August 2012, a total of 205 singleton pregnant women presenting at our antenatal clinic were enrolled in this prospective study and were assessed for baseline demographic and obstetric data. They underwent ultrasound evaluation at the time of second and third trimesters, both included Doppler assessment of bilateral uterine arteries to determine the values of the pulsatility index (PI) and resistance index (RI) and presence of early diastolic notch. The endpoint of this study was assessing the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of Doppler ultrasonography of the uterine artery, for the prediction of adverse pregnancy outcomes including preeclampsia, stillbirth, placental abruption and preterm labor. RESULTS: The mean age of cases was 26.4±5.11. The uterine artery PI and RI values for both second (PI: 1.1±0.42 versus 1.53±0.59, p=0.002; RI: 0.55±0.09 versus 0.72±0.13, p=0.000 respectively) and third-trimester (PI: 0.77±0.31 versus 1.09±0.46, p=0.000; RI: 0.46±0.10 versus 0.60±0.14, p=0.010 respectively) evaluations were significantly higher in patients with adverse pregnancy outcome than in normal women. Combination of PI and RI >95th percentile and presence of bilateral notch in second trimester get sensitivity and specificity of 36.1 and 97% respectively, while these measures were 57.5 and 98.2% in third trimester. CONCLUSIONS: According to our study, it seems that uterine artery Doppler may be a valuable tool for the prediction of a variety of adverse outcomes in second and third trimesters.

A systematic study of the brain base arteries in the turkey (Meleagris gallopavo)

Thirty heads with neck segments of turkeys (Meleagris gallopavo) were dissected for a systematic study of the arteries. The frequency of the arteries found was: Cerebral carotid artery, intercarotid anastomosis and internal ophthalmic artery (100%). Caudal branch of the cerebral carotid artery to the right (R) vestigial artery (70%) and developed (30%) and to the left (L) developed (70%) and vestigial artery (30%). Ventral tectal mesencephalic artery in (70%) to R and (30%) to L was the direct branch of the cerebral carotid artery to L (70%) and to R (30%) collateral branch of the developed caudal branch. Basilar artery to L in (70%) and to R (30%) formed from the developed caudal branch; rostral ventral cerebellar artery present (86.7%) and absent (13.3%) to R and L. Caudal ventral cerebellar artery to R single (73.3%), double (23.3%) and triple (3.3%); caudal ventral cerebellar artery to L single (73.3%) and double (26.7%). Dorsal spinal artery branch of caudal ventral cerebellar artery to R (80%) and to L (73.3%). The rostral branch of cerebral carotid artery showed as collateral branches the single caudal cerebral artery to R (100%) and to L (96.7%) while in (3.3%) it was double. The middle cerebral artery was single to R and L (100%). Cerebroethmoidal artery to R and L (100%) with its collateral branch to single rostral cerebral artery (90%) to R and (86.7%) to L and double (10%) to R and (13.3%) to L. Ethmoidal artery to R and to L (100%) single. The cerebral arterial circle was rostrally and caudally opened, so that the cerebral blood supply was exclusively made by the carotid system.

A systematic study of the brain base arteries in the rabbit (Oryctolagus cuniculus)

The brains of 30 New Zealand rabbits (Oryctolagus cuniculus) were injected with red stained latex. The arteries of the ventral surface of the brain were systematized on the right (R) and on the left (L) side with the respective percentage of appearance: the aortic arch emitted the braquicephalic trunk and the left subclavian artery (83.3%); or the braquicephalic trunk, the left common carotid artery and the left subclavian artery (16.7%). The braquicephalic trunk emitted the right and the left common carotid arteries and the right subclavian artery (83.3%); or the right common carotid artery and the right subclavian artery (16.7%). The common carotid arteries were divided into external and internal carotid arteries (96.7% on the R, 100% on the L.). The internal carotid artery to the R was present (96.7%) and absent (3.3%), and to the L, was present (100%). The rostral choroidal artery to the R was collateral branch of the rostral branch of the internal carotid artery (83.3%), collateral branch of caudal branch of the internal carotid artery (16.7%), and to the L was collateral branch of the rostral branch of the internal carotid artery (93.3%), collateral branch of the caudal branch of the internal carotid artery (6.7%). The middle cerebral artery to the R and to the L was single (80%) and double (20%). The rostral cerebral artery to the R had middle caliber (90%), thin caliber (6.7%) and too thin caliber (3.3%), and to the L had middle caliber (76.7%), thin caliber (16.7%) and too thin caliber (6.7%). The internal ethmoidal artery was absent (73.3%), present and single (26.7%). The caudal cerebral artery to the R was single (66.7%), double (26.7%) and triple (6.7%), and to the L was single (63.3%) and double (36.7%). The terminal branches of the right and left vertebral arteries were present (100%, and formed the basilar artery (100%). The ventral spinal artery was present (100%). The caudal cerebellar artery, to the R was single (43.3%), single with labyrinthic artery isolated (26.7%) and double (30%), and to the L was single (50%), single with labyrinthic artery isolated (6.7%), double (40%) and triple (3.3%). The trigeminal artery to the R and to the L was present (100%). The rostral cerebellar artery to the R was single (53.3%) and double (46,7%), and to the L was single (63.3%) and double (36.7%). The rabbit's cerebral arterial circle was caudally closed (100%) and rostrally closed (93.3%) or opened (6.7%). The brain was supplied by the vertebral-basilar and carotid systems.

Endothelium-dependent vasodilation in response to Pseudomonas aeruginosa lipopolysaccharide: an in vitro study on canine arteries

Early systemic arterial hypotension is a common clinical feature of Pseudomonas septicemia. To determine if Pseudomonas aeruginosa endotoxin induces the release of endothelium-derived nitric oxide (EDNO), an endogenous nitrovasodilator, segments of canine femoral, renal, hepatic, superior mesenteric, and left circumflex coronary arteries were suspended in organ chambers (physiological salt solution, 95% O2/5% CO2, pH 7.4, 37oC) to measure isometric force. In arterial segments contracted with 2 µM prostaglandin F2a, Pseudomonas endotoxin (lipopolysaccharide (LPS) serotype 10(Habs) from Pseudomonas aeruginosa (0.05 to 0.50 mg/ml)) induced concentration-dependent relaxation of segments with endothelium (P<0.05) but no significant change in tension of arteries without endothelium. Endothelium-dependent relaxation in response to Pseudomonas LPS occurred in the presence of 1 µM indomethacin, but could be blocked in the coronary artery with 10 µM NG-monomethyl-L-arginine (L-NMMA), a competitive inhibitor of nitric oxide synthesis from L-arginine. The inhibitory effect of L-NMMA on LPS-mediated vasorelaxation of the coronary artery could be reversed by exogenous 100 µM L-arginine but not by 100 µM D-arginine. These experiments indicate that Pseudomonas endotoxin induces synthesis of nitric oxide from L-arginine by the vascular endothelium. LPS-mediated production of EDNO by the endothelium, possibly through the action of constitutive nitric oxide synthase (NOSc), may decrease systemic vascular resistance and may be the mechanism of early hypotension characteristic of Pseudomonas septicemia.

Computational modeling of stented coronary arteries

The application of computational fluid dynamics (CFD) and finite element analysis (FEA) has been growing rapidly in the various fields of science and technology. One of the areas of interest is in biomedical engineering. The altered hemodynamics inside the blood vessels plays a key role in the development of the arterial disease called atherosclerosis, which is the major cause of human death worldwide. Atherosclerosis is often treated with the stenting procedure to restore the normal blood flow. A stent is a tubular, flexible structure, usually made of metals, which is driven and expanded in the blocked arteries. Despite the success rate of the stenting procedure, it is often associated with the restenosis (re-narrowing of the artery) process. The presence of non-biological device in the artery causes inflammation or re-growth of atherosclerotic lesions in the treated vessels. Several factors including the design of stents, type of stent expansion, expansion pressure, morphology and composition of vessel wall influence the restenosis process. Therefore, the role of computational studies is crucial in the investigation and optimisation of the factors that influence post-stenting complications. This thesis focuses on the stent-vessel wall interactions followed by the blood flow in the post-stenting stage of stenosed human coronary artery. Hemodynamic and mechanical stresses were analysed in three separate stent-plaque-artery models. Plaque was modeled as a multi-layer (fibrous cap (FC), necrotic core (NC), and fibrosis (F)) and the arterial wall as a single layer domain. CFD/FEA simulations were performed using commercial software packages in several models mimicking the various stages and morphologies of atherosclerosis. The tissue prolapse (TP) of stented vessel wall, the distribution of von Mises stress (VMS) inside various layers of vessel wall, and the wall shear stress (WSS) along the luminal surface of the deformed vessel wall were measured and evaluated. The results revealed the role of the stenosis size, thickness of each layer of atherosclerotic wall, thickness of stent strut, pressure applied for stenosis expansion, and the flow condition in the distribution of stresses. The thicknesses of FC, and NC and the total thickness of plaque are critical in controlling the stresses inside the tissue. A small change in morphology of artery wall can significantly affect the distribution of stresses. In particular, FC is the most sensitive layer to TP and stresses, which could determine plaque’s vulnerability to rupture. The WSS is highly influenced by the deflection of artery, which in turn is dependent on the structural composition of arterial wall layers. Together with the stenosis size, their roles could play a decisive role in controlling the low values of WSS (<0.5 Pa) prone to restenosis. Moreover, the time dependent flow altered the percentage of luminal area with WSS values less than 0.5 Pa at different time instants. The non- Newtonian viscosity model of the blood properties significantly affects the prediction of WSS magnitude. The outcomes of this investigation will help to better understand the roles of the individual layers of atherosclerotic vessels and their risk to provoke restenosis at the post-stenting stage. As a consequence, the implementation of such an approach to assess the post-stented stresses will assist the engineers and clinicians in optimizing the stenting techniques to minimize the occurrence of restenosis.

Synchronization of ovulation in crossbred dairy heifers using gonadotrophin-releasing hormone agonist, prostaglandin F2a and human chorionic gonadotrophin or estradiol benzoate

Girolando (Gir x Holstein) is a very common dairy breed in Brazil because it combines the rusticity of Gir (Bos indicus) with the high milk yield of Holstein (Bos taurus). The ovarian follicular dynamics and hormonal treatments for synchronization of ovulation and timed artificial insemination were studied in Girolando heifers. The injection of a gonadotrophin-releasing hormone (GnRH) agonist was followed 6 or 7 days (d) later by prostaglandin F2a (PGF2a). Twenty-four hours after PGF2a injection either human chorionic gonadotropin (hCG, GPh-d6 and GPh-d7 groups) or estradiol benzoate (EB, GPE-d6 and GPE-d7 groups) was administered to synchronize ovulation and consequently allow timed artificial insemination (AI) 24 and 30 h after hCG and EB injection, respectively. Follicular dynamics in Girolando heifers was characterized by the predominance of three follicular waves (71.4%) with sizes of dominant follicles (10-13 mm) and corpus luteum (approximately 20 mm) similar to those for Bos indicus cattle. In the GnRH-PGF-hCG protocol, hCG administration induced earlier ovulation (67.4 h, P<0.01) compared to the control group (GnRH-PGF) and a better synchronization of ovulation, since most of it occurred within a period of 12 to 17 h. Pregnancy rate after timed AI was 42.8 (3/7, GPh-d6) to 50% (7/14, GPh-d7). In contrast, estradiol benzoate (GnRH-PGF-EB protocol) synchronized ovulation of only 5 of 11 heifers from the GPE-d7 group and of none (0/7) from the GPE-d6 group, which led to low pregnancy rates after timed AI (27.3 and 0%, respectively). However, since a small number of Girolando heifers was used to determine pregnancy rates in the present study, pregnancy rates should be confirmed with a larger number of animals.

Measurement of the ultrasonic properties of human coronary arteries in vitro with a 50-MHz acoustic microscope

Ultrasonic attenuation coefficient, wave propagation speed and integrated backscatter coefficient (IBC) of human coronary arteries were measured in vitro over the -6 dB frequency bandwidth (36 to 67 MHz) of a focused ultrasound transducer (50 MHz, focal distance 5.7 mm, f/number 1.7). Corrections were made for diffraction effects. Normal and diseased coronary artery sub-samples (N = 38) were obtained from 10 individuals at autopsy. The measured mean ± SD of the wave speed (average over the entire vessel wall thickness) was 1581.04 ± 53.88 m/s. At 50 MHz, the average attenuation coefficient was 4.99 ± 1.33 dB/mm with a frequency dependence term of 1.55 ± 0.18 determined over the 36- to 67-MHz frequency range. The IBC values were: 17.42 ± 13.02 (sr.m)-1 for thickened intima, 11.35 ± 6.54 (sr.m)-1 for fibrotic intima, 39.93 ± 50.95 (sr.m)-1 for plaque, 4.26 ± 2.34 (sr.m)-1 for foam cells, 5.12 ± 5.85 (sr.m)-1 for media and 21.26 ± 31.77 (sr.m)-1 for adventitia layers. The IBC results indicate the possibility for ultrasound characterization of human coronary artery wall tissue layer, including the situations of diseased arteries with the presence of thickened intima, fibrotic intima and plaque. The mean IBC normalized with respect to the mean IBC of the media layer seems promising for use as a parameter to differentiate a plaque or a thickened intima from a fibrotic intima.

Compensatory enlargement of human coronary arteries identified by magnetic resonance imaging

The aim of the present study was to evaluate the role of magnetic resonance imaging (MRI) for the non-invasive detection of coronary abnormalities and specifically the remodeling process in patients with coronary artery disease (CAD). MRI was performed in 10 control healthy subjects and 26 patients with angiographically proven CAD of the right coronary (RCA) or left anterior descending (LAD) artery; 23 patients were within two months of acute coronary syndromes, and 3 had stable angina with a positive test for ischemia. Wall thickness (WT), vessel wall area (VWA), total vessel area (TVA), and luminal area (LA) were measured. There were significant increases in WT (mean ± SEM, RCA: 2.62 ± 0.75 vs 0.53 ± 0.15 mm; LAD: 2.21 ± 0.69 vs 0.62 ± 0.24 mm) and in VWA (RCA: 30.96 ± 17.57 vs 2.1 ± 1.2 mm²; LAD: 19.53 ± 7.25 vs 3.6 ± 2.0 mm²) patients compared to controls (P < 0.001 for each variable). TVA values were also greater in patients compared to controls (RCA: 44.56 ± 21.87 vs 12.3 ± 4.2 mm²; LAD: 31.89 ± 11.31 vs 17.0 ± 6.2 mm²; P < 0.001). In contrast, the LA did not differ between patients and controls for RCA or LAD. When the LA was adjusted for vessel size using the LA/TVA ratio, a significant difference was found: 0.33 ± 0.16 in patients vs 0.82 ± 0.09 in controls (RCA) and 0.38 ± 0.13 vs 0.78 ± 0.06 (LAD) (P < 0.001). As opposed to normal controls, positive remodeling was present in all patients with CAD, as indicated by larger VWA. We conclude that MRI detected vessel wall abnormalities and was an effective tool for the noninvasive evaluation of the atherosclerotic process and coronary vessel wall modifications, including positive remodeling that frequently occurs in patients with acute coronary syndromes.