Vessel Cross-sectional Area Research Articles

Fetal Loss of Adrenomedullin Causes Maternal Vascular Pathology Typical of Preeclampsia.

Adrenomedullin (AM) is a 52-amino acid peptide vasodilator that is elevated 3 to 5-fold in normal human pregnancies but is often blunted in pregnancy complications such as fetal growth restriction, gestational diabetes, and preeclampsia. Our previous studies have shown that genetic reduction of maternal AM leads to poor pregnancy outcomes, but the role of fetal AM remains unknown. Therefore, we examined placentas of Adm-/- and Adm+/+ pups at midgestation for structural, functional, and developmental phenotypes. Histologic and morphometric analysis revealed normal differentiation and layer formation in the Adm-/- placentas. Doppler ultrasound of umbilical cord blood flow showed that placental impedance was unaffected by fetal loss of Adm. Although histology and lectin staining showed no difference in the total cross-sectional area of fetal and maternal vessels, the fetal vessels of the Adm-/- placentas were large and underbranched compared to those of wildtype littermates. Electron microscopy of methyl-methacrylate casts confirmed that Adm-/- placentas had reduced fetal vessel branching; a hallmark feature of preeclampsia. Strikingly, the Adm-/- placentas also had reduced numbers of decidual natural killer (NK) cells and reduced remodeling of maternal spiral arteries; other known features of preeclampsia. To further investigate the effects of AM signaling on NK cells, isolated primary NK cells were treated with AM, which resulted in significantly altered cytokine expression compared to untreated controls. Primary smooth muscle cell cultures exposed to supernatant from AM-treated NK cells also showed a significant increase in smooth muscle cell apoptosis, indicating that the AM-mediated change in NK cell cytokine expression may be required for normal spiral artery remodeling. To confirm that this phenotype is specific to lack of fetal AM, ovarian transplantation was performed from Adm+/- to Adm+/+ females. The placentas of Adm-/- pups from wildtype mothers receiving heterozygote ovary transplants recapitulated the reduced NK cell invasion and failed spiral artery remodeling originally seen in heterozygous mothers, demonstrating that lack of AM specifically from the fetal compartment is responsible for the observed preeclampsia-like pathology. Furthermore, we were able to rescue this phenotype by generating a transgenic mouse model with increased fetal AM expression, termed Admhi/hi. High fetal AM led to recruitment of increased decidual NK cells and normal spiral artery remodeling. RT-PCR screening revealed that numerous cytokines known to play important roles in the placenta had opposite regulation in Admhi/hi versus Adm-/- placentas. Taken together, these data indicate that loss of fetal AM causes reduced fetal vascularization and maternal spiral artery remodeling characteristic of preeclampsia, and that these phenotypes can be rescued by overexpressing fetal AM. These findings demonstrate that the dosage of fetal AM is a critical factor for adapting the maternal vasculature to pregnancy and may be important in preventing the development of preeclampsia. This work is supported by The Burroughs Wellcome Fund, NIH/NICHD RO1 HD46970, HD060860, NIH/NHLBI F30 HL104778, and the March of Dimes Foundation. (poster)

Flicker-induced changes in retinal blood flow assessed by Doppler optical coherence tomography

We used Doppler Fourier-domain optical coherence tomography (OCT) to investigate flicker-induced changes of total retinal blood flow. Total retinal blood flow was measured by summing flows in veins imaged in double-circular scans around the optic disc. In 3 healthy volunteers, total retinal blood flow was measured before and 10-15 seconds after 30 seconds of flicker stimulation. The average blood flow increased 22.2% (p = 0.002). The total venous and arterial vessel cross-sectional area increased 11.3% (p < 0.001) and +2.7% (p = 0.28) respectively. The average venous and arterial flow velocity were calculated indirectly by dividing total retinal blood flow by total venous and arterial cross-sectional areas. They also increased by 8.8% (p = 0.046) and 18.3% (p = 0.004), respectively. These results show that human retinal blood flow increases after visible flicker stimulation, and this could be measured with OCT.

Flicker-induced changes in retinal blood flow assessed by Doppler optical coherence tomography

We used Doppler Fourier-domain optical coherence tomography (OCT) to investigate flicker-induced changes of total retinal blood flow. Total retinal blood flow was measured by summing flows in veins imaged in double-circular scans around the optic disc. In 3 healthy volunteers, total retinal blood flow was measured before and 10-15 seconds after 30 seconds of flicker stimulation. The average blood flow increased 22.2% (p = 0.002). The total venous and arterial vessel cross-sectional area increased 11.3% (p < 0.001) and +2.7% (p = 0.28) respectively. The average venous and arterial flow velocity were calculated indirectly by dividing total retinal blood flow by total venous and arterial cross-sectional areas. They also increased by 8.8% (p = 0.046) and 18.3% (p = 0.004), respectively. These results show that human retinal blood flow increases after visible flicker stimulation, and this could be measured with OCT.

Quantitative computed tomographic measurement of a cross-sectional area of a small pulmonary vessel in nonsmokers without airflow limitation

Pulmonary vascular alterations are not exclusive to pulmonary vascular disorders; they are also present in patients with mild chronic obstructive pulmonary disease (COPD) with normal pulmonary function. Moreover, vascular alteration is closely related to lung ventilation. We hypothesized that pulmonary vascular alterations might occur even in nonsmokers with subtle airflow limitation, and there could be a significant correlation between pulmonary vascular alterations and airflow impairment. The purpose of this study was to evaluate the correlation between the vascular alterations measured by cross-sectional area (CSA) and airflow impairment in nonsmokers with normal pulmonary function. Thirty patients (1 man, 29 women; mean age 55 ± 14 years, range 33-81 years) underwent pulmonary function tests (PFTs) within 2 weeks of undergoing multidetector computed tomography (CT) scans. Total vessel CSA < 5 mm(2) was calculated by a threshold technique using imaging software. Forced expiratory volume in 1 s (FEV(1)), the ratio of FEV(1) to FVC (FEV(1)/FVC), and the mid-expiratory phase of the forced expiratory flow (FEF(25%-75%)) were obtained from PFTs. We calculated Spearman correlation coefficients between %CSA < 5 and the results of PFTs. %CSA < 5 had a significant positive correlation with FEV(1)/FVC (r = 0.651, P < 0.0001) and FEF(25%-75%) (r = 0.627, P = 0.0002), whereas CSA < 5% had no significant correlation with FEV(1) (r = 0.172, P = 0.362). There was a significant correlation between pulmonary small vascular alteration and airflow impairment even in nonsmokers without airway obstruction.

Comparison of intravascular ultrasound and x-ray computed tomography of the thoracic aorta: Correlation with ischemic heart disease and risk factors

To compare plaque and calcification of the thoracic aorta with ischemic heart disease and risk factors, the authors used intravascular ultrasound (IVUS) and X-ray computed tomography (CT). The study included 29 patients (24 males and 5 females, mean age 61 ± 11 years): 21 with ischemic heart disease (IHD) and 8 with valvular disease or dilated cardiomyopathy. A Sonicath Ultra 6 imaging catheter (12.5 MHz, Scimed) was inserted through the femoral artery, and IVUS images were obtained around the descending aorta at the level of the pulmonary artery bifurcation. Percent plaque area (%PA) was calculated as vessel cross sectional area (CSA) surrounded by media minus lumen CSA divided by vessel CSA. The CVIS clear view system (Scimed) was used for image analysis. CT without contrast enhancement was performed from the aortic arch to the diaphragm in horizontal sections of 1 cm. The number of slices showing aortic calcification was determined as the CT calcification score. Coronary angiography (CAG) was also performed in each patient, and the authors analyzed the correlation of these imaging modalities with IHD with multiple risk factors. In the descending aorta the IVUS probe was not eccentric and gave accurate images of plaque. In the ascending aorta or aortic arch, the probe was somewhat eccentric. Plaque was observed to be diffuse without discrete lesions. The %PA was 2.5–28.6 (14.9 ± 5.5) %, and the CT score was 0–25 (8.2 ± 7.9). The %PA and CT score showed a significant correlation with each other (r = 0.57, p <0.05) and with age (r = 0.44 and 0.64, respectively, p <0.05). Neither showed a significant correlation with findings from CAG or risk factors. IVUS accurately detects the presence and extent of plaque in the thoracic aorta. The %PA shows a significant correlation with CT-detected calcification of the aorta. Neither calcification nor plaque is correlated with IHD or risk factors. IVUS-detected plaque and CT-detected calcification are strongly influenced by age.

Assessment of coronary artery remodelling by dual-source CT: a head-to-head comparison with intravascular ultrasound

BackgroundWhile it is widely assumed that coronary CT angiography permits detection and quantification of ‘positive remodelling’ of coronary atherosclerotic lesions, there is a paucity of data comparing CT with established...

First‐trimester assessment of umbilical vein diameter using the semiautomated system for nuchal translucency measurement

We read with great interest the articles recently published in this journal on the possibility of obtaining semiautomated measurements of nuchal translucency (NT)1-3. These studies demonstrate that, in the range of NT thickness between 1.5 and 3 mm, this new technique significantly improves the reproducibility of measurements. Although NT measurement is the cornerstone of the first-trimester ultrasound examination, it is also possible during this same gestational period to quantify absolute umbilical vein (UV) flow4, 5, and there is evidence that a reduction in UV flow is associated with subsequent impaired fetal growth5. However, the quality of ultrasound measurement of UV diameter is crucial in the calculation of absolute blood flow. Indeed, small errors in measurement of UV diameter may result in large errors in absolute flow computation, since vessel cross-sectional area is proportional to the square of the diameter. Since during the first trimester UV size is in the same range as that of NT, we tested the hypothesis that the software developed to semiautomatically measure NT may also be useful for measurement of UV diameter. To this end, after obtaining written informed consent from the mothers, we examined 50 consecutive fetuses undergoing the 11 + 0 to 13 + 6 weeks' ultrasound scan using an Aloka Prosound Alpha 7 machine with a 6-MHz transabdominal probe (Aloka, Tokyo, Japan). Using a previously reported technique6 the image of the fetal abdomen was magnified and the UV was visualized by perpendicularly insonating its intra-abdominal portion. Images were then stored on the hard disk of the ultrasound equipment. In each set of 50 images, two investigators (G.R. and A.C.) measured the UV diameter offline twice manually and twice with the semiautomated method (Figure 1). The two series of measurements were obtained 1 week apart. Manual measurements were obtained by placing the electronic calipers of the ultrasound equipment inner to inner at the point of maximal size of the UV. For the automated assessment the measurement box was placed on a rectilinear portion of the intra-abdominal UV, and the system automatically calculated the maximum diameter between superior and inferior borders (Figure 1). For each investigator the intraobserver reliability of the two manual and the two semiautomated measurements was assessed by the within-operator SD, calculated as the SD of the differences between the two measurements divided by √2. Interclass correlation coefficients (ICC) were used to assess interobserver reliability. Transverse view of the fetal abdomen at 12 + 5 weeks showing the measurement box placed over the umbilical vein (UV). The automated system draws two lines on the inner borders of the umbilical vein and measures the maximum UV diameter. For both investigators the within-operator SD values were significantly reduced with the semiautomated method (G.R.: manual, 0.111 (95% CI, 0.091–0.131) vs. semiautomated, 0.047 (95% CI, 0.036–0.059), P < 0.0001; A.C.: manual, 0.123 (95% CI, 0.091–0.154) vs. semiautomated, 0.049 (95% CI, 0.013–0.084), P < 0.0001). An improvement in the interobserver reliability was also seen when using the semiautomated method (manual ICC 0.883 vs. semiautomated ICC 0.957). In conclusion, the semiautomated system developed for NT measurement, when applied to UV diameter measurement, substantially reduces the within- and between-observer variation when compared with the traditional manual method. However, the process of UV measurement is greatly affected by the quality of image acquisition, a factor that requires appropriate sonographer training. Although these difficulties cannot be overcome by automated techniques7, their use may greatly enhance the clinical applications of UV flow assessment by trained operators. G. Rizzo* , A. Capponi* , E. Aiello , D. Arduini , * Fetal Medicine Center, Genoma Molecular Genetics Laboratory, Rome, Italy, Department of Obstetrics and Gynecology, Università di Roma ‘Tor Vergata’, Rome, Italy, Department of Obstetrics and Gynecology, Ospedale G.B. Grassi, Rome, Italy

Maternal dietary choline deficiency alters angiogenesis in fetal mouse hippocampus

We examined whether maternal dietary choline modulates angiogenesis in fetal brain. Pregnant C57BL/6 mice were fed either a choline‐deficient (CD), control (CT), or choline‐supplemented diet (CS) from days 12 to 17 (E12‐17) of pregnancy and then fetal brains were studied. In CD fetal hippocampus, proliferation of endothelial cells (EC) was decreased by 32% (p &lt; 0.01 vs. CT or CS) while differentiated EC clusters (expressing factor VIII related antigen (RA)) increased by 25% (p &lt; 0.01 vs. CT or CS). These changes were associated with &gt; 25% decrease in the number of blood vessels in CD fetal hippocampus (p &lt; 0.01 vs. CT and CS), with no change in total cross‐sectional area of these blood vessels. Expression of genes for the angiogenic signals derived from both endothelial and neuronal progenitor cells (NPC) was increased in CD fetal hippocampus VEGF C (Vegfc), 2.0‐fold, p &lt; 0.01 vs. CT and angiopoietin 2 (Angpt2), 2.1‐fold, (p &lt; 0.01 vs. CT)). Similar increased expression was observed in NPC isolated from E14 fetal mouse brains and exposed to low (5 μM), CT (70 μM), or high choline (280 μM) media for 72 h (low choline caused a 9.7‐fold increase in relative gene expression of Vegfc (p &lt; 0.001 vs. CT and high) and a 3.4‐fold increase in expression of Angpt2, (p &lt; 0.05 vs. CT and high). ANGPT2 protein was increased 42.2% (p &lt; 0.01). Cytosine‐phosphate‐guanine dinucleotide islands in the proximity of the promoter areas of Vegfc and Angpt2 were hypomethylated in low choline NPC compared to CT NPC (p &lt; 0.01). We conclude that maternal dietary choline intake alters angiogenesis in the developing fetal hippocampus. This work was supported by Grants from the National Institutes of Health AG09525, DK55865, and DK56350 (to S.H.Z.) and Pilot Grant ES010126‐08 (to M.G.M.)

CAMP Phosphodiesterase Inhibitors Increases Nitric Oxide Production by Modulating Dimethylarginine Dimethylaminohydrolases

Pulmonary arterial hypertension is characterized by a progressive increase in pulmonary vascular resistance caused by endothelial dysfunction, inward vascular remodeling, and severe loss of precapillary pulmonary vessel cross-sectional area. Asymmetrical dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, and its metabolizing enzyme dimethylarginine dimethylaminohydrolase (DDAH) play important roles in endothelial dysfunction. We investigated whether combined phosphodiesterase (PDE) 3 and 4 inhibition ameliorates endothelial function by regulating the ADMA-DDAH axis. We investigated the effects of the PDE3/4 inhibitor tolafentrine in vitro on endothelial cell survival, proliferation, and apoptosis. Effects of tolafentrine on the endothelial nitric oxide synthase/nitric oxide pathway, DDAH expression, DDAH promoter activity, and cytokine release from endothelial cells and their subsequent influence on DDAH expression were investigated. In monocrotaline-induced pulmonary arterial hypertension in rats, the effects of inhaled tolafentrine on DDAH expression and activity were investigated. Real-time-polymerase chain reaction, immunocytochemistry, and PDE activity assays suggested high expression of PDE3 and PDE4 isoforms in endothelial cells. Treatment of endothelial cells with PDE3/4 inhibitor significantly decreased ADMA-induced apoptosis via a cAMP/PKA-dependent pathway by induction of DDAH2. Chronic nebulization of PDE3/4 inhibitor significantly attenuated monocrotaline-induced hemodynamic, gas exchange abnormalities, vascular remodeling, and right heart hypertrophy. Interestingly, PDE3/4 inhibitor treatment reduced ADMA and elevated nitric oxide/cGMP levels. Mechanistically, this could be attributed to direct modulatory effects of cAMP on the promoter region of DDAH2, which was consequently found to be increased in expression and activity. Furthermore, PDE3/4 inhibitor suppressed apoptosis in endothelial cells and increased vascularization in the lung. Combined inhibition of PDE3 and 4 regresses development of pulmonary hypertension and promotes endothelial regeneration by modulating the ADMA-DDAH axis.

Optically quantified cerebral blood flow

In vivo imaging allows detailed studies of cerebral blood flow and brain metabolism in both normal and pathological states. Since the 1980s, several methods to measure tissue perfusion in the brain have been introduced. Magnetic resonance imaging (MRI) techniques such as blood oxygen level dependent MRI (BOLD MRI) (Sorensen et al, 1995) and arterial spin labeling (Buxton and Frank 1997) as well as micro-positron emission tomography (Heiss et al, 1994) have enabled noninvasive chronic imaging of both regional blood flow changes and absolute perfusion in both humans and animal models. These methods, however, suffer from poor spatial resolution and are mainly useful when studying regional blood flow in the brain. Intrinsic optical imaging (Ts'o et al, 1990) enables higher spatial resolution mapping of changes in blood volume. Laser Doppler spectroscopy (Eyre et al, 1988) enables measurement of relative changes in blood flow speeds averaged over ∼1-mm2 cortical areas, while laser speckle contrast imaging (Boas and Dunn, 2010) enables these relative blood flow changes to be imaged with a spatial resolution of <100 μm. None of these optical techniques, however, can accurately resolve changes in flow in individual microvessels or determine the absolute perfusion of cortical tissue. When absolute speed measurement of individual vessels is required, two-photon excited fluorescence (2PEF) microscopy has been the tool of choice (Schaffer et al, 2006). It is, however, limited to measurement of flow speed in vessels that are oriented parallel to the imaging plane, and measurements need to be made one vessel at a time, which is a time-consuming process. Currently lacking is an imaging technique that enables absolute blood flow speed measurements in multiple individual vessels at once. In this issue of JCBFM, Srinivasan et al (2011) introduce the use of Doppler optical coherence tomography (DOCT) (Chen et al, 1997) to fill this gap. Srinivasan et al demonstrated DOCT as a viable technique to quantify blood flow across many individual vessels simultaneously in the brain of live, anesthetized rodents. Doppler optical coherence tomography measures the Doppler shift of light scattered off from moving red blood cells to quantify flow speeds, with three-dimensional spatial resolution obtained from the use of coherence tomography to isolate the signal from a single axial location and laser scanning to map the two lateral dimensions. Using this tool, absolute blood flow velocity can be rapidly determined in blood vessels that contain an axial projection. In their article, Srinivasan et al demonstrated that DOCT measurements of flow speed and vessel cross-sectional area showed conservation of volumetric flow along non-branching and branching vascular segments, confirming the quantitative accuracy of the method. They further demonstrated that DOCT enables straightforward measurement of blood flow speed in penetrating arterioles and ascending venules (the vessels most difficult to characterize with 2PEF), with all these vessels being within an ∼1-mm2 field of view measured in an ∼1-min-long scan (as opposed to 2PEF, which allows measurement of only one vessel every few minutes). To obtain a quantitative estimate of tissue perfusion, the authors summed the volumetric flow from all ascending venules in a patch of cortex and estimated the cortical volume that is served by these vessels. They found strong correlation between this DOCT measurement of tissue perfusion and the values obtained from a standard hydrogen clearance method (von Kummer et al, 1986). The DOCT measurements, however, consistently yielded higher values for tissue perfusion, likely reflecting depressed blood flow due to tissue damage from the electrode used for hydrogen clearance measurements. The DOCT technique was best suited to measurements in the top 150 μm of the brain and in larger blood vessels rather than in capillaries, and the technique is optimal for flow speeds between ∼0.5 and 10 mm/s with current DOCT systems. Overall, the approach of summing the volumetric flow measured by DOCT of all the ascending venules in a patch of cortex appears to provide a robust tool for minimally invasive measurements of absolute brain tissue perfusion with a spatial resolution that is not matched by previous methods, opening the door to studies of how blood flow is altered at the microvascular scale by physiological and pathophysiological events in the brain.

Verification of a one-dimensional finite element method for modeling blood flow in the cardiovascular system incorporating a viscoelastic wall model

In this study we present the implementation and verification of a space–time finite element method for solving the nonlinear one-dimensional (1-D) equations of blood flow incorporating a viscoelastic arterial wall model. The viscoelastic model used is based on the generalized Maxwell model and thin-walled tube theory assumptions. Verification of the implementation was conducted using two different methods: (1) the analytic solution to the linearized 1-D equations of blood flow and (2) the Method of Manufactured Solutions (MMS). MMS enables verification for conditions such as tapered vessel geometries with spatially varying wall properties which cannot be verified with the analytic solution. RMS error values for all variables of interest (blood flow rate, pressure and vessel cross-sectional area) were calculated for simulations that utilized different mesh and time step sizes. The error values decreased with each mesh and time step size refinement. A theoretical analysis of numerical dissipation was also carried out for the linearized 1-D equations of blood flow. Dissipation in simulations due to different time step sizes matched theoretical estimations for given frequencies. This dissipation analysis can provide one way to estimate mesh and time step sizes to control numerical dissipation in the nonlinear simulations. The presence of wall viscoelasticity in all simulations is clearly seen in the hysteresis (pressure–area) loops.

Quantification of coronary stenosis by dual source computed tomography in patients: A comparative study with intravascular ultrasound and invasive angiography

To determine the accuracy of dual-source CT (DSCT) to quantify coronary stenosis compared to intravascular ultrasound (IVUS) and quantitative coronary angiography (QCA). 21 patients (23 vessels) were examined with DSCT, IVUS and invasive coronary angiography. Coronary minimal luminal diameter (MLD) and area (MLA) were measured in cross-sectional multi-planar reformatted images perpendicular to the vessel long-axis. The vessel cross-sectional area stenosis (MLA/CSA ratio) was calculated. DSCT results were compared with IVUS and QCA. A good correlation between DSCT and IVUS was noted for diameter and area stenosis (r=0.69 and r=0.73), with an overestimation of MLD stenosis by DSCT (+9.1%) and an underestimation of MLA stenosis (-5.8%). For MLD and MLA, high correlation coefficients (r=0.78 and r=0.90, respectively) were found between DSCT and IVUS; and the bias was almost zero (-0.41 mm and +0.1mm(2), respectively). The correlation between DSCT and QCA was moderate (r=0.60) for MLD stenosis with minor overestimation by DSCT (+4.0%) and moderate (r=0.59) for MLD (bias, +0.01 mm). The cross-sectional area stenosis showed a moderate correlation (r=0.59) between DSCT and IVUS (+0.00). DSCT allows accurate quantification of coronary stenosis as compared to IVUS. An excellent correlation was found for the MLA between DSCT and IVUS.

Linear and Nonlinear Viscoelastic Modeling of Aorta and Carotid Pressure–Area Dynamics Under In Vivo and Ex Vivo Conditions

A better understanding of the biomechanical properties of the arterial wall provides important insight into arterial vascular biology under normal (healthy) and pathological conditions. This insight has potential to improve tracking of disease progression and to aid in vascular graft design and implementation. In this study, we use linear and nonlinear viscoelastic models to predict biomechanical properties of the thoracic descending aorta and the carotid artery under ex vivo and in vivo conditions in ovine and human arteries. Models analyzed include a four-parameter (linear) Kelvin viscoelastic model and two five-parameter nonlinear viscoelastic models (an arctangent and a sigmoid model) that relate changes in arterial blood pressure to the vessel cross-sectional area (via estimation of vessel strain). These models were developed using the framework of Quasilinear Viscoelasticity (QLV) theory and were validated using measurements from the thoracic descending aorta and the carotid artery obtained from human and ovine arteries. In vivo measurements were obtained from 10 ovine aortas and 10 human carotid arteries. Ex vivo measurements (from both locations) were made in 11 male Merino sheep. Biomechanical properties were obtained through constrained estimation of model parameters. To further investigate the parameter estimates, we computed standard errors and confidence intervals and we used analysis of variance to compare results within and between groups. Overall, our results indicate that optimal model selection depends on the artery type. Results showed that for the thoracic descending aorta (under both experimental conditions), the best predictions were obtained with the nonlinear sigmoid model, while under healthy physiological pressure loading the carotid arteries nonlinear stiffening with increasing pressure is negligible, and consequently, the linear (Kelvin) viscoelastic model better describes the pressure-area dynamics in this vessel. Results comparing biomechanical properties show that the Kelvin and sigmoid models were able to predict the zero-pressure vessel radius; that under ex vivo conditions vessels are more rigid, and comparatively, that the carotid artery is stiffer than the thoracic descending aorta; and that the viscoelastic gain and relaxation parameters do not differ significantly between vessels or experimental conditions. In conclusion, our study demonstrates that the proposed models can predict pressure-area dynamics and that model parameters can be extracted for further interpretation of biomechanical properties.

Coronary Vessel and Luminal Area Measurement Using Dual-Source Computed Tomography in Comparison With Intravascular Ultrasound

Image display settings (window and level) have a substantial impact on measurements of coronary artery and plaque dimensions in computed tomography (CT), and their influence on measurement accuracy has not been systematically evaluated. We analyzed the influence of window width/level settings on the accuracy for determining cross-sectional lumen and outer vessel diameters in contrast-enhanced CT angiography compared with intravascular ultrasound (IVUS). We evaluated the data sets of 35 patients. Coronary CT angiography was performed as part of a research protocol before invasive coronary angiography. A contrast-enhanced volume data set was acquired using a dual-source CT (DSCT) scanner (Siemens Healthcare, Forchheim, Germany). Intravascular ultrasound was performed using a 40-MHz IVUS catheter (Atlantis, Boston Scientific Corporation, Natick, Mass) and motorized pullback at 0.5 mm/s. One hundred exactly corresponding sites within the coronary artery system were identified in both DSCT and IVUS using bifurcation points as fiducial markers. In DSCT data sets, multiplanar reconstructions (0.75-mm slice thickness) were rendered orthogonally to the centerline of the coronary artery at each of the 100 sites. Computed tomographic images were displayed using 4 previously published settings (700/200, 700/140, and 500/150 Hounsfield units [HU], and 1 HU/65% of the mean luminal intensity [HU] and 155%/65% of the mean luminal intensity [HU] for window width/level) as well as with a visually adjusted setting for subjectively optimal lumen and outer vessel area measurement. Coronary lumen and cross-sectional vessel areas were manually traced using all 5 display settings and compared with IVUS measurements. Concerning cross-sectional vessel area measurements, correlation was close and significant compared with IVUS using all settings (r ≥ 0.93, P = 0.01 for all settings). Bland-Altman analysis revealed a good agreement between both modalities with a systematic bias toward overestimation in CT. Least bias was demonstrated using the setting 155%/65% of the mean luminal intensity for window width/level, with a mean (SD) difference of 0.2 (1.73) mm2. For the measurement of the luminal area, the window setting using a width of 1 HU and a level of 65% of the mean luminal intensity showed the lowest correlation to IVUS (r = 0.85), with a systematic bias toward underestimation of the lumen in CT. Bland-Altman analysis revealed a moderate agreement with a mean (SD) difference of -2.1 (1.6) mm2. For all other settings, a very close correlation was observed (r > 0.9, P = 0.01), and Bland-Altman analysis revealed a slight trend toward lumen underestimation in CT, yet with a good agreement. The least bias was demonstrated using the setting 700/200 HU for window width/level with a mean (SD) difference of -0.1 (0.9) mm2. Previously published window settings and visually adjusted window setting correlate very well with IVUS measurements regarding coronary artery cross-sectional and luminal area, with a better agreement for luminal area measurements. A systematic bias toward overestimation of vessel area in CT was observed as well as a slight trend toward lumen underestimation. This bias was least for vessel area measurement using 155%/65% of the mean luminal intensity (HU) for window width/level, whereas for luminal area measurement, the setting 700/200 HU for window width/level yielded the least bias.

頸動脈におけるｔｉｍｅ−ｏｆ−ｆｌｉｇｈｔ ＭＲ ａｎｇｉｏｇｒａｐｈｙとＣＴ ａｎｇｉｏｇｒａｐｈｙによる血管の断面積と径の評価

In carotid artery stenosis, precisely assessing the vessel cross-sectional area and diameter is important because this result determines the treatment strategy for patients. The purpose of our study was to evaluate the vessel sizes of normal and stenotic carotid arteries using time-of-flight magnetic resonance angiography (TOF-MRA) and X-ray CT angiography (CTA). The TOF-MRA and the CTA data were obtained using 3D TOF-MRA on a 1.5-T MR scanner (1.0 mm slice thickness) and dynamic contrast-enhanced multi-detector row CT (0.5 mm slice thickness). In thirty-three normal patients (20 men, 13 women, mean age of 66.9±9.0 years) and eighteen patients with carotid artery stenosis (12 men, 6 women, mean age of 74.4±6.4 years), we measured the vessel cross-sectional areas and the diameters of the internal and common carotid arteries (ICAs and CCAs) using TOF-MRA and CTA and a vessel-analytic program of the workstation. The mean cross-sectional areas and diameters of normal ICAs and CCAs determined using TOF-MRA were significantly smaller than those determined using CTA. The percentages of area and diameter stenoses found using TOF-MRA were 7.7 and 14.3% higher than those found using CTA. In six cases in the stenotic group, the stenotic artery showed no signal using TOF-MRA, but the CTA depicted it. In both normal and stenotic carotid arteries, TOF-MRA underestimates vessel size more than CTA does.

Retinal Arteriolar Geometry is Associated with Cerebral White Matter Hyperintensities on Magnetic Resonance Imaging

BackgroundCerebral small vessel disease (lacunar stroke and cerebral white matter hyperintensities) is caused by vessel abnormalities of unknown aetiology. Retinal vessels show developmental and pathophysiological similarities to cerebral small vessels and microvessel geometry may influence vascular efficiency.HypothesisRetinal arteriolar branching angles or coefficients (the ratio of the sum of the cross-sectional areas of the two daughter vessels to the cross-sectional area of the parent vessel at an arteriolar bifurcation) may be associated with cerebral small vessel disease.MethodsWe performed a cross-sectional observational study in a UK tertiary referral hospital. An experienced stroke physician recruited consecutive patients presenting with lacunar ischaemic stroke with a control group consisting of patients with minor cortical ischaemic stroke. We performed brain magnetic resonance imaging to assess the recent infarct and periventricular and deep white matter hyperintensities. We subtyped stroke with clinical and radiological findings. We took digital retinal photographs to assess retinal arteriolar branching coefficients and branching angles using a semi-automated technique.ResultsTwo hundred and five patients were recruited (104 lacunar stroke, 101 cortical stroke), mean age 68-years (standard deviation 12). With multivariate analysis, increased branching coefficient was associated with periventricular white matter hyperintensities (P=0·006) and ischaemic heart disease (P<0·001), and decreased branching coefficient with deep white matter hyperintensities (P=0·003), but not with lacunar stroke subtype (P=0·96). We found no associations with retinal branching angles.ConclusionsRetinal arteriolar geometry differs between cerebral small vessel phenotypes. Further research is needed to ascertain the clinical significance of these findings.

The Relationship between Small Pulmonary Vascular Alteration and Aortic Atherosclerosis in Chronic Obstructive Pulmonary Disease: Quantitative CT Analysis

The relationship between chronic obstructive pulmonary disease (COPD) and atherosclerosis has been suggested; this association may relate to systemic inflammation and endothelial dysfunction, which can lead to alteration of small pulmonary vessels. The relationship between atherosclerosis and small pulmonary vessel alteration, however, has not been assessed in COPD patients. We tested the hypothesis that the severity of thoracic aortic calcification measured by computed tomography (CT) would be associated with the total cross-sectional area of small pulmonary vessels (CSA) on CT images. The study was approved by the institutional review board and was Health Insurance Portability and Accountability Act-compliant. Informed consent was waived. For 51 COPD patients enrolled in the National Heart, Lung, and Blood Institute Lung Tissue Research Consortium, we calculated the percentage of total CSAs of less than 5 mm² for the total lung area (%CSA<5). Thoracic aortic calcification, quantified by modified Agatston score, was measured. The correlations between thoracic aortic calcification score and %CSA<5, pulmonary function, and extent of emphysema were evaluated. Multiple linear regression analysis using aortic calcification score as the dependent outcome was also performed. The %CSA<5 had a significant negative correlation with the thoracic aortic calcification score (r = -0.566, P < .0001). Multiple linear regression analysis showed significant correlation between the aortic calcification score and %CSA<5 (P < .0001) independent of age, pack-years, extent of emphysema, and FEV1%. Atherosclerosis, assessed by aortic calcification, is associated with the small pulmonary vascular alteration in COPD. Systemic inflammation and endothelial dysfunction may cause the close relationship between atherosclerosis and small pulmonary vessel alteration.

Linking root morphology, longevity and function to root branch order: a case study in three shrubs

Root branching order supports a powerful approach to understanding complex root systems; however, how the pattern of root morphological characteristics, tissue carbon (C) and nitrogen (N) concentrations, and root lifespan are related to anatomical features of variable root orders for mature shrubs (∼19 years old) in sandy habitats is still unclear. In this study, these relationships were investigated for three typical shrubs in Horqin Sand Land, Northeast China. Root diameter, individual root length, tissue carbon concentration, C:N ratio, root lifespan, root cross-sectional area (CSA), stele CSA, proportion of stele in root CSA, mean xylem vessel CSA and the number of xylem vessels all increased with root order for the three shrubs, while specific root length and nitrogen concentration decreased with root order. The combined root biomass of the first two orders accounted for more than 63% of the first–fourth order root biomass for all the three shrubs. Proportion of stele to root CSA and number of xylem vessels of third-order root segments were significantly higher than that of the first two orders, and third-order roots showed secondary development with a continuous cork layer. All first-order and most second-order roots exhibited primary development, had an intact cortex, a lower proportion of stele to root CSA, and a smaller number of vessels. Our research suggests that the first two order roots of shrubs in sandy habitats are responsible mainly for absorption, and that they play a major role in root turnover and C and N flux in the soil organic matter pool due to their high proportion of biomass and N concentration, as well as their short lifespan.

Maternal dietary choline deficiency alters angiogenesis in fetal mouse hippocampus.

We examined whether maternal dietary choline modulates angiogenesis in fetal brain. Pregnant C57BL/6 mice were fed either a choline-deficient (CD), control (CT), or choline-supplemented diet (CS) from days 12 to 17 (E12-17) of pregnancy and then fetal brains were studied. In CD fetal hippocampus, proliferation of endothelial cells (EC) was decreased by 32% (p < 0.01 vs. CT or CS) while differentiated EC clusters (expressing factor VIII related antigen (RA)) increased by 25% (p < 0.01 vs. CT or CS). These changes were associated with > 25% decrease in the number of blood vessels in CD fetal hippocampus (p < 0.01 vs. CT and CS), with no change in total cross-sectional area of these blood vessels. Expression of genes for the angiogenic signals derived from both endothelial and neuronal progenitor cells (NPC) was increased in CD fetal hippocampus VEGF C (Vegfc), 2.0-fold, p < 0.01 vs. CT and angiopoietin 2 (Angpt2), 2.1-fold, (p < 0.01 vs. CT)). Similar increased expression was observed in NPC isolated from E14 fetal mouse brains and exposed to low (5 microM), CT (70 microM), or high choline (280 microM) media for 72 h (low choline caused a 9.7-fold increase in relative gene expression of Vegfc (p < 0.001 vs. CT and high) and a 3.4-fold increase in expression of Angpt2, (p < 0.05 vs. CT and high). ANGPT2 protein was increased 42.2% (p < 0.01). Cytosine-phosphate-guanine dinucleotide islands in the proximity of the promoter areas of Vegfc and Angpt2 were hypomethylated in low choline NPC compared to CT NPC (p < 0.01). We conclude that maternal dietary choline intake alters angiogenesis in the developing fetal hippocampus.

Do changes in gastro‐intestinal blood flow explain high‐altitude anorexia?

Gastrointestinal symptoms are common on acute exposure to high-altitude (HA). Underlying mechanisms are not understood, but vascular shunting away from the gut could be responsible. Therefore, blood flow in the superior mesenteric artery (SMA) and hepatic portal vein (HPV) was examined at sea level (SL) and after ascent to 4392 m (HA). Twelve subjects [eight male, mean age 40 (22-72) years] were studied following an overnight fast and a standard meal. Cross-sectional vessel area and blood velocity were measured by ultrasound, systolic and diastolic flow calculated for the SMA (HR x vessel area x velocity, cm(3) min(-1)) and mean flow for the HPV. All subjects experienced reduced appetite at HA. Blood flow in the SMA and HPV increased following food at SL (mean SMA systolic flow 1024 vs. 3316 cm(3) min(-1), P < 0.001; HPV 505 vs. 1789, P < 0.001) and at HA (2020 vs. 3767, P < 0.001; HPV 708 vs. 1727, P < 0.001). Pre-prandial flow in the SMA and HPV was significantly increased at HA compared with SL. The changes were due to increased vessel diameter and increased flow velocity. There was no difference in post-prandial flow between SL and HA in the HPV, although the increase in post-prandial flow was greater at SL than HA (254% increase vs. 144%). These results show that resting blood flow in the gastrointestinal tract is increased during exposure to high-altitude hypoxia, and that the vascular response of increased blood flow following food ingestion is maintained. Therefore, reduced flow is unlikely to cause gastrointestinal symptoms and reduced appetite at HA.