A prospective observational study comparing a non-operator dependent automatic PWV analyser to pulse pressure, in assessing arterial stiffness in hemodialysis.

BACKGROUND: Chronic kidney disease (CKD) accelerates vascular stiffening related to age. Arterial stiffness may be evaluated measuring the carotid-femoral pulse wave velocity (PWV) or more simply, as recommended by KDOQI, monitoring pulse pressure (PP). Both correlate to survival and incidence of cardiovascular disease. PWV can also be estimated on the brachial artery using a Mobil-O-Graph; a non-operator dependent automatic device. The aim was to analyse whether, in a dialysis population, PWV obtained by Mobil-O-Graph (MogPWV) is more sensitive for vascular aging than PP. METHODS: A cohort of 143 patients from 4 dialysis units has been followed measuring MogPWV and PP every 3 to 6 months and compared to a control group with the same risk factors but an eGFR > 30 ml/min. RESULTS: MogPWV contrarily to PP did discriminate the dialysis population from the control group. The mean difference translated in age between the two populations was 8.4 years. The increase in MogPWV, as a function of age, was more rapid in the dialysis group. 13.3% of the dialysis patients but only 3.0% of the control group were outliers for MogPWV. The mortality rate (16 out of 143) was similar in outliers and inliers (7.4 and 8.0%/year). Stratifying patients according to MogPWV, a significant difference in survival was seen. A high parathormone (PTH) and to be dialysed for a hypertensive nephropathy were associated to a higher baseline MogPWV. CONCLUSIONS: Assessing PWV on the brachial artery using a Mobil-O-Graph is a valid and simple alternative, which, in the dialysis population, is more sensitive for vascular aging than PP. As demonstrated in previous studies PWV correlates to mortality. Among specific CKD risk factors only PTH is associated with a higher baseline PWV. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02327962.

Extra Forces induced by wide-pulse, high-frequency electrical stimulation: Occurrence, magnitude, variability and underlying mechanisms.

OBJECTIVE: In contrast to conventional (CONV) neuromuscular electrical stimulation (NMES), the use of "wide-pulse, high-frequencies" (WPHF) can generate higher forces than expected by the direct activation of motor axons alone. We aimed at investigating the occurrence, magnitude, variability and underlying neuromuscular mechanisms of these "Extra Forces" (EF). METHODS: Electrically-evoked isometric plantar flexion force was recorded in 42 healthy subjects. Additionally, twitch potentiation, H-reflex and M-wave responses were assessed in 13 participants. CONV (25Hz, 0.05ms) and WPHF (100Hz, 1ms) NMES consisted of five stimulation trains (20s on-90s off). RESULTS: K-means clustering analysis disclosed a responder rate of almost 60%. Within this group of responders, force significantly increased from 4% to 16% of the maximal voluntary contraction force and H-reflexes were depressed after WPHF NMES. In contrast, non-responders showed neither EF nor H-reflex depression. Twitch potentiation and resting EMG data were similar between groups. Interestingly, a large inter- and intrasubject variability of EF was observed. CONCLUSION: The responder percentage was overestimated in previous studies. SIGNIFICANCE: This study proposes a novel methodological framework for unraveling the neurophysiological mechanisms involved in EF and provides further evidence for a central contribution to EF in responders.

1C.06: Ambulatory pulse pressure is negatively associated with excretions of urinary caffeine and its metabolites

OBJECTIVE: Systolic blood pressure (BP) has been associated with urinary caffeine and its metabolites such as paraxanthine and theophylline. Caffeine and caffeine metabolites could influence arterial pulse pressure (PP) via sympathomimetic effects, smooth muscle relaxation, and phosphodiesterase inhibition. The purpose of this analysis was to explore the association of ambulatory PP with urinary caffeine and its related metabolites in a large population-based sample. DESIGN AND METHOD: Families were randomly selected from the general population of three Swiss cities (2009-2013). Ambulatory BP monitoring was conducted using validated Diasys Integra devices. PP was defined as the difference between the systolic and diastolic ambulatory BP. Urinary caffeine, paraxanthine, theophylline, and theobromine excretions were measured in 24 h urine using ultra-high performance liquid chromatography tandem mass spectrometry. Urinary excretions were log-transformed to satisfy regression assumptions. We used linear mixed models to explore the associations of urinary caffeine and caffeine metabolite excretions with 24-hour, day- and night-time PP while adjusting for major confounders. RESULTS: The 836 participants (48.9% men) included in this analysis had mean (±SD) age of 47.8 (±17.5), and mean 24-hour systolic and diastolic BP of 120.1 mmHg (±13.9) and 78.0 (±8.6). Except theobromine, log transformed urinary caffeine and caffeine metabolite excretions were associated negatively with 24-hour, daytime and night-time ambulatory PP. 24-hour, daytime, and night-time ambulatory PP decreased by -0.804 mmHg (SE, 0.209), -0.749 (0.215), and -0.968 (0.243) (all P values <0.005), for each doubling excretion of caffeine. Strong negative associations with night-time ambulatory PP were observed for paraxanthine and theophylline.(Figure is included in full-text article.) CONCLUSIONS: : The negative associations of PP with caffeine, paraxanthine, and theophylline excretions suggest that caffeine and its metabolites do lower BP, possibly by modifying arterial stiffness.

Impact of body tilt on the central aortic pressure pulse

Le but de cette thèse a été d'investiguer la relation entre, d'une part le temps de propagation de l'onde de pouls artérielle du coeur vers les membres inférieurs, et d'autre part le temps séparant, au niveau de l'aorte ascendante, la génération de l'onde antérograde du retour des ondes réfléchies. Le principe de la méthode employée a été de mesurer ces deux temps par deux méthodes indépendantes, ce en les faisant varier par changement rapide de la position du corps, chez sujets humains volontaires. Le facteur gravitationnel a en effet une influence majeure sur la pression transmurale des artères, dont dépend largement la vitesse de propagation des ondes de pouls, tant dans le sens antérograde que rétrograde. Vingt sujets jeunes, en bonne santé, dontIO hommes et 10 femmes, ont été examinés sur une table de tilt, dans deux positions différentes : tête vers le bas (angle de tilt : - 10°) et tête vers le haut (+45°).Dans chaque position, le temps de propagation carotido- femorale (Tcf, succédané du temps aorto-fémoral) et carotido-tibial (Tct, succédané du temps aorto-tibial) a été mesuré avec l'appareil Complior. De même, dans chaque position la pression aortique centrale a été enregistrée par tonométrie radiale en utilisant l'appareil SphygmoCor qui applique une fonction de transfert généralisé pour reconstruire la forme de l'onde de pouls aortique. L'analyse de celle-ci permet ensuite de calculer les temps d'aller-retour des ondes réfléchies atteignant l'aorte pendant la systole (début de l'onde réfléchie, sT1 r) et pendant la diastole (temps de transit moyen de l'onde diastolique réfléchie dMTT). Le changement de position de tête vers le haut à tête vers le bas, a provoqué une augmentation importante du temps de propagation Tct (chez le femmes de 130±10 à 185±18msec, P<0,001 et chez les hommes de 136±9 à 204±18msec P<0.001) ainsi que du temps moyen de transition de l'onde diastolique réfléchie dMTT (chez les femmes de 364±35 à 499±33msec P<0,001 et chez les hommes de 406±22 à 553±21msec, P<0,001). Un modèle de régression mixte montre qu'entre les deux positions, les variations de dMTT sont environ le double de celles de Tct (coefficient de régression 2.1; 95% intervalle de confiance 1.9-2,3, P<0,001). Ces résultats suggèrent que les ondes diastoliques observées dans l'onde de pouls aortique central reconstruites par tonométrie radiale, correspondent, du moins en partie, aux ondes réfléchies générées au niveau des membres inférieurs.

Study and modelling of the effect of herbicides pulse exposure on freshwater microalgae

De plus en plus de substances chimiques sont émises et détectées dans l'environnement.Parmi ces substances, on trouve les herbicides qui sont utilisés en agriculture pour luttercontre la présence des mauvaises herbes. Après leur application sur les sols, les herbicidespeuvent être entrainés par les eaux de pluie jusque dans les ruisseaux et les rivières. Lesconcentrations de ces substances varient donc de manière importante dans les systèmesaquatiques en période de pluie ou en période de temps sec. Des pics élevés de concentrationssont suivis de période de concentrations très faibles ou nulles. Les herbicides présents dans lescours d'eau peuvent engendrer des effets toxiques sur les algues et les plantes aquatiques. Orles tests classiques d'écotoxicologie effectués en laboratoire sont réalisés en exposant lesespèces vivantes à des polluants de manière continue. Ils ne permettent donc pas d'évaluer leseffets des concentrations fluctuantes comme celles des herbicides. Le but de cette thèse estd'étudier et de modéliser les effets des concentrations fluctuantes d'herbicide sur les espècesde microalgues vertes Scenedesmus vacuolatus et Pseudokirchneriella subcapitata. Desexpériences en laboratoire ont également été effectuées dans le but de valider le modèle.Quatre herbicides ont été testés. Il s'agit de l'atrazine (utilisé jusqu'à récemment pour lemaïs), du diuron (utilisé dans la vigne), de l'isoproturon (utilisé pour les céréales) et du Smétolachlore(utilisé pour le maïs). Les résultats de ce travail de thèse indiquent que les effetsdes concentrations fluctuantes d'herbicide peuvent être modélisés sur des algues d'eau douce.Le modèle est relativement simple pour les inhibiteurs de la photosynthèse tels que l'atrazine,le diuron ou l'isoproturon. Il nécessite la connaissance de deux paramètres, le taux decroissance de l'algue sans polluant et la courbe dose-réponse pour chaque substance.Cependant, des expériences supplémentaires doivent être réalisées si la substance étudiéeinduit un délai de l'effet et du rétablissement ou si une algue est cultivée avec une autre alguedans le même milieu de croissance. Le modèle pourrait également être adapté pour tenircompte des mélanges de substances. Appliqué pour prédire les effets sur les algues descénarios réels, le modèle montre que les longs pics de concentrations jouent le rôle le plusimportant. Il est donc crucial de les mesurer lors du monitoring des cours d'eau. D'autre part,une évaluation du risque effectuée avec ce modèle montre que l'impact des pics deconcentrations sur les espèces les plus sensibles est total. Cela met en évidence, une fois deplus, l'importance de tenir compte de ces concentrations fluctuantes dans l'évaluation durisque environnemental des herbicides, mais également des autres polluants.

Responders to Wide-Pulse, High-Frequency Neuromuscular Electrical Stimulation Show Reduced Metabolic Demand: A 31P-MRS Study in Humans.

Conventional (CONV) neuromuscular electrical stimulation (NMES) (i.e., short pulse duration, low frequencies) induces a higher energetic response as compared to voluntary contractions (VOL). In contrast, wide-pulse, high-frequency (WPHF) NMES might elicit-at least in some subjects (i.e., responders)-a different motor unit recruitment compared to CONV that resembles the physiological muscle activation pattern of VOL. We therefore hypothesized that for these responder subjects, the metabolic demand of WPHF would be lower than CONV and comparable to VOL. 18 healthy subjects performed isometric plantar flexions at 10% of their maximal voluntary contraction force for CONV (25 Hz, 0.05 ms), WPHF (100 Hz, 1 ms) and VOL protocols. For each protocol, force time integral (FTI) was quantified and subjects were classified as responders and non-responders to WPHF based on k-means clustering analysis. Furthermore, a fatigue index based on FTI loss at the end of each protocol compared with the beginning of the protocol was calculated. Phosphocreatine depletion (ΔPCr) was assessed using 31P magnetic resonance spectroscopy. Responders developed four times higher FTI's during WPHF (99 ± 37 ×103 N.s) than non-responders (26 ± 12 ×103 N.s). For both responders and non-responders, CONV was metabolically more demanding than VOL when ΔPCr was expressed relative to the FTI. Only for the responder group, the ∆PCr/FTI ratio of WPHF (0.74 ± 0.19 M/N.s) was significantly lower compared to CONV (1.48 ± 0.46 M/N.s) but similar to VOL (0.65 ± 0.21 M/N.s). Moreover, the fatigue index was not different between WPHF (-16%) and CONV (-25%) for the responders. WPHF could therefore be considered as the less demanding NMES modality-at least in this subgroup of subjects-by possibly exhibiting a muscle activation pattern similar to VOL contractions.

Impact of body tilt on the central aortic pressure pulse.

The present work was undertaken to investigate, in young healthy volunteers, the relationships between the forward propagation times of arterial pressure waves and the timing of reflected waves observable on the aortic pulse, in the course of rapid changes in body position. 20 young healthy subjects, 10 men, and 10 women, were examined on a tilt table at two different tilt angles, -10° (Head-down) and + 45° (Head-up). In each position, carotid-femoral (Tcf) and carotid-tibial forward propagation times (Tct) were measured with the Complior device. In each position also, the central aortic pressure pulse was recorded with radial tonometry, using the SphygmoCor device and a generalized transfer function, so as to evaluate the timing of reflected waves reaching the aorta in systole (onset of systolic reflected wave, sT1r) and diastole (mean transit time of diastolic reflected wave, dMTT). The position shift from Head-up to Head-down caused a massive increase in both Tct (women from 130 ± 10 to 185 ± 18 msec P < 0.001, men from 136 ± 9 to 204 ± 18 msec P < 0.001) and dMTT (women from 364 ± 35 to 499 ± 33 msec P < 0.001, men from 406 ± 22 to 553 ± 21 msec P < 0.001). Mixed model regression showed that the changes in Tct and dMTT observed between Head-up and Head-down were tightly coupled (regression coefficient 2.1, 95% confidence interval 1.9-2.3, P < 0.001). These results strongly suggest that the diastolic waves observed on central aortic pulses reconstructed from radial tonometric correspond at least in part to reflections generated in the lower limbs.

Development of metabolic labeling strategies to study changes in protein expression

Résumé : Les progrès techniques de la spectrométrie de masse (MS) ont contribué au récent développement de la protéomique. Cette technique peut actuellement détecter, identifier et quantifier des milliers de protéines. Toutefois, elle n'est pas encore assez puissante pour fournir une analyse complète des modifications du protéome corrélées à des phénomènes biologiques. Notre objectif était le développement d'une nouvelle stratégie pour la détection spécifique et la quantification des variations du protéome, basée sur la mesure de la synthèse des protéines plutôt que sur celle de la quantité de protéines totale. Pour cela, nous volions associer le marquage pulsé des protéines par des isotopes stables avec une méthode d'acquisition MS basée sur le balayage des ions précurseurs (precursor ion scan, ou PIS), afin de détecter spécifiquement les protéines ayant intégré les isotopes et d'estimer leur abondance par rapport aux protéines non marquées. Une telle approche peut identifier les protéines avec les plus hauts taux de synthèse dans une période de temps donnée, y compris les protéines dont l'expression augmente spécifiquement suite à un événement précis. Nous avons tout d'abord testé différents acides aminés marqués en combinaison avec des méthodes PIS spécifiques. Ces essais ont permis la détection spécifique des protéines marquées. Cependant, en raison des limitations instrumentales du spectromètre de masse utilisé pour les méthodes PIS, la sensibilité de cette approche s'est révélée être inférieure à une analyse non ciblée réalisée sur un instrument plus récent (Chapitre 2.1). Toutefois, pour l'analyse différentielle de deux milieux de culture conditionnés par des cellules cancéreuses humaines, nous avons utilisé le marquage métabolique pour distinguer les protéines d'origine cellulaire des protéines non marquées du sérum présentes dans les milieux de culture (Chapitre 2.2). Parallèlement, nous avons développé une nouvelle méthode de quantification nommée IBIS, qui utilise des paires d'isotopes stables d'acides aminés capables de produire des ions spécifiques qui peuvent être utilisés pour la quantification relative. La méthode IBIS a été appliquée à l'analyse de deux lignées cellulaires cancéreuses complètement marquées, mais de manière différenciée, par des paires d'acides aminés (Chapitre 2.3). Ensuite, conformément à l'objectif initial de cette thèse, nous avons utilisé une variante pulsée de l'IBIS pour détecter des modifications du protéome dans des cellules HeLa infectée par le virus humain Herpes Simplex-1 (Chapitre 2.4). Ce virus réprime la synthèse des protéines des cellules hôtes afin d'exploiter leur mécanisme de traduction pour la production massive de virions. Comme prévu, de hauts taux de synthèse ont été mesurés pour les protéines virales détectées, attestant de leur haut niveau d'expression. Nous avons de plus identifié un certain nombre de protéines humaines dont le rapport de synthèse et de dégradation (S/D) a été modifié par l'infection virale, ce qui peut donner des indications sur les stratégies utilisées par les virus pour détourner la machinerie cellulaire. En conclusion, nous avons montré dans ce travail que le marquage métabolique peut être employé de façon non conventionnelle pour étudier des dimensions peu explorées en protéomique. Summary : In recent years major technical advancements greatly supported the development of mass spectrometry (MS)-based proteomics. Currently, this technique can efficiently detect, identify and quantify thousands of proteins. However, it is not yet sufficiently powerful to provide a comprehensive analysis of the proteome changes correlated with biological phenomena. The aim of our project was the development of ~a new strategy for the specific detection and quantification of proteomé variations based on measurements of protein synthesis rather than total protein amounts. The rationale for this approach was that changes in protein synthesis more closely reflect dynamic cellular responses than changes in total protein concentrations. Our starting idea was to couple "pulsed" stable-isotope labeling of proteins with a specific MS acquisition method based on precursor ion scan (PIS), to specifically detect proteins that incorporated the label and to simultaneously estimate their abundance, relative to the unlabeled protein isoform. Such approach could highlight proteins with the highest synthesis rate in a given time frame, including proteins specifically up-regulated by a given biological stimulus. As a first step, we tested different isotope-labeled amino acids in combination with dedicated PIS methods and showed that this leads to specific detection of labeled proteins. Sensitivity, however, turned out to be lower than an untargeted analysis run on a more recent instrument, due to MS hardware limitations (Chapter 2.1). We next used metabolic labeling to distinguish the proteins of cellular origin from a high background of unlabeled (serum) proteins, for the differential analysis of two serum-containing culture media conditioned by labeled human cancer cells (Chapter 2.2). As a parallel project we developed a new quantification method (named ISIS), which uses pairs of stable-isotope labeled amino acids able to produce specific reporter ions, which can be used for relative quantification. The ISIS method was applied to the analysis of two fully, yet differentially labeled cancer cell lines, as described in Chapter 2.3. Next, in line with the original purpose of this thesis, we used a "pulsed" variant of ISIS to detect proteome changes in HeLa cells after the infection with human Herpes Simplex Virus-1 (Chapter 2.4). This virus is known to repress the synthesis of host cell proteins to exploit the translation machinery for the massive production of virions. As expected, high synthesis rates were measured for the detected viral proteins, confirming their up-regulation. Moreover, we identified a number of human proteins whose synthesis/degradation ratio (S/D) was affected by the viral infection and which could provide clues on the strategies used by the virus to hijack the cellular machinery. Overall, in this work, we showed that metabolic labeling can be employed in alternative ways to investigate poorly explored dimensions in proteomics.

Regulation of Nedd4-2 self-ubiquitination and stability by a PY motif located within its HECT-domain.

Ubiquitin ligases play a pivotal role in substrate recognition and ubiquitin transfer, yet little is known about the regulation of their catalytic activity. Nedd4 (neural-precursor-cell-expressed, developmentally down-regulated 4)-2 is an E3 ubiquitin ligase composed of a C2 domain, four WW domains (protein-protein interaction domains containing two conserved tryptophan residues) that bind PY motifs (L/PPXY) and a ubiquitin ligase HECT (homologous with E6-associated protein C-terminus) domain. In the present paper we show that the WW domains of Nedd4-2 bind (weakly) to a PY motif (LPXY) located within its own HECT domain and inhibit auto-ubiquitination. Pulse-chase experiments demonstrated that mutation of the HECT PY-motif decreases the stability of Nedd4-2, suggesting that it is involved in stabilization of this E3 ligase. Interestingly, the HECT PY-motif mutation does not affect ubiquitination or down-regulation of a known Nedd4-2 substrate, ENaC (epithelial sodium channel). ENaC ubiquitination, in turn, appears to promote Nedd4-2 self-ubiquitination. These results support a model in which the inter- or intra-molecular WW-domain-HECT PY-motif interaction stabilizes Nedd4-2 by preventing self-ubiquitination. Substrate binding disrupts this interaction, allowing self-ubiquitination of Nedd4-2 and subsequent degradation, resulting in down-regulation of Nedd4-2 once it has ubiquitinated its target. These findings also point to a novel mechanism employed by a ubiquitin ligase to regulate itself differentially compared with substrate ubiquitination and stability.

Subcellular investigation of photosynthesis-driven carbon assimilation in the symbiotic reef coral Pocillopora damicornis.

Reef-building corals form essential, mutualistic endosymbiotic associations with photosynthetic Symbiodinium dinoflagellates, providing their animal host partner with photosynthetically derived nutrients that allow the coral to thrive in oligotrophic waters. However, little is known about the dynamics of these nutritional interactions at the (sub)cellular level. Here, we visualize with submicrometer spatial resolution the carbon and nitrogen fluxes in the intact coral-dinoflagellate association from the reef coral Pocillopora damicornis by combining nanoscale secondary ion mass spectrometry (NanoSIMS) and transmission electron microscopy with pulse-chase isotopic labeling using [(13)C]bicarbonate and [(15)N]nitrate. This allows us to observe that (i) through light-driven photosynthesis, dinoflagellates rapidly assimilate inorganic bicarbonate and nitrate, temporarily storing carbon within lipid droplets and starch granules for remobilization in nighttime, along with carbon and nitrogen incorporation into other subcellular compartments for dinoflagellate growth and maintenance, (ii) carbon-containing photosynthates are translocated to all four coral tissue layers, where they accumulate after only 15 min in coral lipid droplets from the oral gastroderm and within 6 h in glycogen granules from the oral epiderm, and (iii) the translocation of nitrogen-containing photosynthates is delayed by 3 h. IMPORTANCE: Our results provide detailed in situ subcellular visualization of the fate of photosynthesis-derived carbon and nitrogen in the coral-dinoflagellate endosymbiosis. We directly demonstrate that lipid droplets and glycogen granules in the coral tissue are sinks for translocated carbon photosynthates by dinoflagellates and confirm their key role in the trophic interactions within the coral-dinoflagellate association.

T1-weighted MRI as a substitute to CT for refocusing planning in MR-guided focused ultrasound.

Precise focusing is essential for transcranial MRI-guided focused ultrasound (TcMRgFUS) to minimize collateral damage to non-diseased tissues and to achieve temperatures capable of inducing coagulative necrosis at acceptable power deposition levels. CT is usually used for this refocusing but requires a separate study (CT) ahead of the TcMRgFUS procedure. The goal of this study was to determine whether MRI using an appropriate sequence would be a viable alternative to CT for planning ultrasound refocusing in TcMRgFUS. We tested three MRI pulse sequences (3D T1 weighted 3D volume interpolated breath hold examination (VIBE), proton density weighted 3D sampling perfection with applications optimized contrasts using different flip angle evolution and 3D true fast imaging with steady state precision T2-weighted imaging) on patients who have already had a CT scan performed. We made detailed measurements of the calvarial structure based on the MRI data and compared those so-called 'virtual CT' to detailed measurements of the calvarial structure based on the CT data, used as a reference standard. We then loaded both standard and virtual CT in a TcMRgFUS device and compared the calculated phase correction values, as well as the temperature elevation in a phantom. A series of Bland-Altman measurement agreement analyses showed T1 3D VIBE as the optimal MRI sequence, with respect to minimizing the measurement discrepancy between the MRI derived total skull thickness measurement and the CT derived total skull thickness measurement (mean measurement discrepancy: 0.025; 95% CL (-0.22-0.27); p = 0.825). The T1-weighted sequence was also optimal in estimating skull CT density and skull layer thickness. The mean difference between the phase shifts calculated with the standard CT and the virtual CT reconstructed from the T1 dataset was 0.08 ± 1.2 rad on patients and 0.1 ± 0.9 rad on phantom. Compared to the real CT, the MR-based correction showed a 1 °C drop on the maximum temperature elevation in the phantom (7% relative drop). Without any correction, the maximum temperature was down 6 °C (43% relative drop). We have developed an approach that allows for a reconstruction of a virtual CT dataset from MRI to perform phase correction in TcMRgFUS.

Influence of age, risk factors, and cardiovascular and renal disease on arterial stiffness: clinical applications.

Age is the main clinical determinant of large artery stiffness. Central arteries stiffen progressively with age, whereas peripheral muscular arteries change little with age. A number of clinical studies have analyzed the effects of age on aortic stiffness. Increase of central artery stiffness with age is responsible for earlier wave reflections and changes in pressure wave contours. The stiffening of aorta and other central arteries is a potential risk factor for increased cardiovascular morbidity and mortality. Arterial stiffening with aging is accompanied by an elevation in systolic blood pressure (BP) and pulse pressure (PP). Although arterial stiffening with age is a common situation, it has now been confirmed that older subjects with increased arterial stiffness and elevated PP have higher cardiovascular morbidity and mortality. Increase in aortic stiffness with age occurs gradually and continuously, similarly for men and women. Cross-sectional studies have shown that aortic and carotid stiffness (evaluated by the pulse wave velocity) increase with age by approximately 10% to 15% during a period of 10 years. Women always have 5% to 10% lower stiffness than men of the same age. Although large artery stiffness increases with age independently of the presence of cardiovascular risk factors or other associated conditions, the extent of this increase may depend on several environmental or genetic factors. Hypertension may increase arterial stiffness, especially in older subjects. Among other cardiovascular risk factors, diabetes type 1 and 2 accelerates arterial stiffness, whereas the role of dyslipidemia and tobacco smoking is unclear. Arterial stiffness is also present in several cardiovascular and renal diseases. Patients with heart failure, end stage renal disease, and those with atherosclerotic lesions often develop central artery stiffness. Decreased carotid distensibility, increased arterial thickness, and presence of calcifications and plaques often coexist in the same subject. However, relationships between these three alterations of the arterial wall remain to be explored.

Diffusion-weighted MR imaging of the spine at 3-T: feasibility, optimization of b-value and utility to differentiate benign from pathological vertebral compression fractures

Purpose: To evaluate the feasibility, determine the optimal b-value, and assess the utility of 3-T diffusion-weighted MR imaging (DWI) of the spine in differentiating benign from pathologic vertebral compression fractures.Methods and Materials: Twenty patients with 38 vertebral compression fractures (24 benign, 14 pathologic) and 20 controls (total: 23 men, 17 women, mean age 56.2years) were included from December 2010 to May 2011 in this IRB-approved prospective study. MR imaging of the spine was performed on a 3-T unit with T1-w, fat-suppressed T2-w, gadolinium-enhanced fat-suppressed T1-w and zoomed-EPI (2D RF excitation pulse combined with reduced field-of-view single-shot echo-planar readout) diffusion-w (b-values: 0, 300, 500 and 700s/mm2) sequences. Two radiologists independently assessed zoomed-EPI image quality in random order using a 4-point scale: 1=excellent to 4=poor. They subsequently measured apparent diffusion coefficients (ADCs) in normal vertebral bodies and compression fractures, in consensus.Results: Lower b-values correlated with better image quality scores, with significant differences between b=300 (mean±SD=2.6±0.8), b=500 (3.0±0.7) and b=700 (3.6±0.6) (all p<0.001). Mean ADCs of normal vertebral bodies (n=162) were 0.23, 0.17 and 0.11×10-3mm2/s with b=300, 500 and 700s/mm2, respectively. In contrast, mean ADCs were 0.89, 0.70 and 0.59×10-3mm2/s for benign vertebral compression fractures and 0.79, 0.66 and 0.51×10-3mm2/s for pathologic fractures with b=300, 500 and 700s/mm2, respectively. No significant difference was found between ADCs of benign and pathologic fractures.Conclusion: 3-T DWI of the spine is feasible and lower b-values (300s/mm2) are recommended. However, our preliminary results show no advantage of DWI in differentiating benign from pathologic vertebral compression fractures.

Repositioning precision of coronary arteries measured on X-ray angiography and its implications for coronary MR angiography.

BACKGROUND: To test the hypothesis that intervals with superior beat-to-beat coronary artery repositioning precision exist in the cardiac cycle, to design a coronary MR angiography (MRA) methodology in response, and to ascertain its performance. METHODS: Coronary repositioning precision in consecutive heartbeats was measured on x-ray coronary angiograms of 17 patients and periods with the highest repositioning precision were identified. In response, the temporal order of coronary MRA pulse sequence elements required modification and the T2 -prep now follows (T2 -post) rather than precedes the imaging part of the sequence. The performance of T2 -post was quantitatively compared (signal-to-noise [SNR], contrast-to-noise [CNR], vessel sharpness) to that of T2 -prep in vivo. RESULTS: Coronary repositioning precision is <1 mm at peak systole and in mid diastole. When comparing systolic T2 -post to diastolic T2 -prep, CNR and vessel sharpness remained unchanged (both P = NS) but SNR for muscle and blood increased by 104% and 36% (both P < 0.05), respectively. CONCLUSION: Windows with improved coronary repositioning precision exist in the cardiac cycle: one in peak systole and one in mid diastole. Peak-systolic imaging necessitates a re-design of conventional coronary MRA pulse sequences and leads to image quality very similar to that of conventional mid-diastolic data acquisition but improved SNR. J. Magn. Reson. Imaging 2015;41:1251-1258. © 2014 Wiley Periodicals, Inc.

Decreased compliance on arterial anastomoses.

The present study was undertaken to examine the cross-sectional vascular compliance at the anastomotic site. METHODS AND MATERIAL: We performed end-to-end anastomosis on the carotid artery of six pigs using continuous 6/0 polypropylene. Four carotid arteries were excised and mounted in a perfusion chamber while the remaining two were left in living animals. We used pulsed ultrasound (NIUS 02) to generate detailed longitudinal profiles of diameter and compliance in the proximity and on the anastomosis. RESULTS: On the anastomosis, the vessel diameter decreases (-1 to -2.6% of diastolic diameter) when blood pressure increases with an exponential correlation (R2 = 0.75). The arterial compliance at the anastomosis was negative: the vessel cross-section reduction for a pulse pressure of 1 up to 32 mmHg was 0.9 to 2% of diastolic vessel cross-section. CONCLUSIONS: Vessel movement generated a dynamic stenosis whose magnitude seems to depend on blood pressure level. Increasing blood pressure causes the retraction of vessel ends which causes vessel lumen reduction. These results suggest that continuous suture does not provide the continuity of mechanical properties of the artery.