Magnus Cinthio

Evaluation of an ultrasonic echo-tracking method for measurements of arterial wall movements in two dimensions

The longitudinal movement of blood vessel walls has so far gained little or no attention, as it has been presumed that these movements are of a negligible magnitude. However, modern high-resolution ultrasound scanners can demonstrate that the inner layers of the arterial wall exhibit considerable movements in the longitudinal direction. This paper evaluates a new, noninvasive, echo-tracking technique, which simultaneously can track both the radial and the longitudinal movements of the arterial wall with high resolution in vivo. Initially, the method is evaluated in vitro using a specially designed ultrasound phantom, which is attached to and moved by an X-Y system, the movement of which was compared with two high-resolution triangulation lasers. The results show an inaccuracy of 2.5% full scale deflection (fsd), reproducibility of 12 /spl mu/m and a resolution of 5 /spl mu/m, which should be more than sufficient for in vivo studies. The ability of the method is also demonstrated in a limited in vivo study in which a preselected part of the inner vessel wall of the right common carotid artery of a healthy volunteer is tracked in two dimensions over many cardiac cycles. The results show well reproducible x-y movement loops in which the recorded radial and longitudinal movements both are of the magnitude millimetre.

Hemoglobin induces inflammation after preterm intraventricular hemorrhage by methemoglobin formation

BackgroundCerebral intraventricular hemorrhage (IVH) is a major cause of severe neurodevelopmental impairment in preterm infants. To date, no therapy is available that prevents infants from developing serious neurological disability following IVH. Thus, to develop treatment strategies for IVH, it is essential to characterize the initial sequence of molecular events that leads to brain damage. In this study, we investigated extracellular hemoglobin (Hb) as a causal initiator of inflammation in preterm IVH.MethodsUsing a preterm rabbit pup model, we investigated the molecular mechanisms and events following IVH. We also characterized the concentrations of cell-free Hb metabolites and pro-inflammatory mediators in the cerebrospinal fluid (CSF) of preterm human infants and rabbit pups. Finally, Hb metabolites were evaluated as causal initiators of inflammation in primary rabbit astrocyte cell cultures.ResultsFollowing IVH in preterm rabbit pups, the intraventricular CSF concentration of cell-free methemoglobin (metHb) increased from 24 to 72 hours and was strongly correlated with the concentration of TNFα at 72 hours (r2 = 0.896, P <0.001). Also, the mRNA expression of TNFα, IL-1β, and Toll-like receptor-4 and TNFα protein levels were significantly increased in periventricular tissue at 72 hours, which was accompanied by extensive astrocyte activation (that is, glial fibrillary acidic protein (GFAP)staining). Furthermore, exposure of primary rabbit astrocyte cell cultures to metHb caused a dose-dependent increase in TNFα mRNA and protein levels, which was not observed following exposure to oxyhemoglobin (oxyHb) or hemin. Finally, a positive correlation (r2 = 0.237, P <0.03) between metHb and TNFα concentrations was observed in the CSF of preterm human infants following IVH.ConclusionsFollowing preterm IVH, increased metHb formation in the intraventricular space induces expression of pro-inflammatory cytokines. Thus, the formation of metHb might be a crucial initial event in the development of brain damage following preterm IVH. Accordingly, removal, scavenging, or neutralization of Hb could present a therapeutic opportunity and plausible approach to decreasing the damage in the immature brain following preterm IVH.

Longitudinal displacement and intramural shear strain of the porcine carotid artery undergo profound changes in response to catecholamines

The effects of catecholamines on longitudinal displacements and intramural shear strain of the arterial wall are unexplored. Therefore, the common carotid artery of five anaesthetized pigs was investigated using an in-house developed noninvasive ultrasonic technique. The study protocol included intravenous infusion of low-dose epinephrine (β-adrenoceptor activation), as well as intravenous boluses of norepinephrine (α-adrenoceptor activation). Further, the effects of β-blockade (metoprolol) were studied. There were significant positive correlations between pulse pressure and longitudinal displacement of the intima-media complex (r = 0.72; P < 0.001), as well as between pulse pressure and intramural shear strain (r = 0.48; P < 0.001). Following administration of norepinephrine, the longitudinal displacement of the intima-media complex and intramural shear strain profoundly increased (median 190%, range 102-296%, and median 141%, range 101-182%, respectively, compared with baseline), also when given during β-blockade (median 228%, range 133-266%, and median 158%, range 152-235%, respectively). During infusion of low-dose epinephrine, the longitudinal displacement of the intima-media complex and intramural shear strain decreased (median 88%, range 69-122%, and median 69%, range 47-117%, respectively, compared with baseline). In conclusion, the present study shows, for the first time, that the longitudinal displacement and intramural shear strain of the porcine carotid artery undergo profound changes in response to catecholamines. Increase in longitudinal displacements seems to be strongly related to α-adrenoceptor activation. Thus metoprolol is insufficient to counteract a profound increase in longitudinal displacement and intramural shear strain following a surge of norepinephrine.

Intra-observer variability of longitudinal displacement and intramural shear strain measurements of the arterial wall using ultrasound noninvasively in vivo.

Using a recently developed high-resolution noninvasive ultrasonic method, we recently demonstrated that the intima-media complex of the common carotid artery show a bidirectional multiphasic longitudinal displacement of the same magnitude as the diameter change during the cardiac cycle. The longitudinal movement of the adventitial region was smaller, thus, we identified shear strain and, thus, shear stress, within the arterial wall. The aim of this study was to evaluate the intra-observer variability of measurement of the longitudinal displacement of the intima-media complex and the intramural shear strain of the common carotid artery in vivo using the new ultrasonic method. The evaluation was carried out by comparing two consecutive measurements on the common carotid artery of 20 healthy human subjects. According to the method of Bland Altman, we show that the systematic and random differences for the different phases of movement are acceptable in comparison to the measured displacement and no significant differences between the two measurements could be detected (p > 0.05 for all measured parameters). The coefficient of variation (CV) for measurement of the different phases of movement was <or=16%, including short-term physiologic variations. The higher variability in the measurement of the intramural shear strain (CV = 24%) has several explanations, which are discussed. In conclusion, this study shows that the present first ultrasonic method for high-resolution measurement of the longitudinal movement of the arterial wall is reliable and satisfactory for the further research of the longitudinal movement of the arterial wall in vivo. Further studies on the longitudinal movement of the arterial wall are important for developing an improved understanding of the physiology and the pathophysiology of the cardiovascular system.

Effects of adrenaline on longitudinal arterial wall movements and resulting intramural shear strain: a first report

Using ultrasound we recently demonstrated that in central elastic arteries as well as in large muscular arteries in humans there is a distinct longitudinal displacement of the arterial wall during the cardiac cycle. Further, for the first time, we also demonstrated that the inner parts of the vessel wall, the intima‐media complex, in these vessels exhibit a larger longitudinal displacement than the outer part of the vessel wall, the adventitial region, introducing the presence of substantial shear strain, and thus shear stress within the vessel wall. The role of these unexplored phenomena is unknown. Here, in a first study on the longitudinal movements of the porcine common carotid artery, we show that administration of adrenaline (epinephrine) might have pronounced effects on the longitudinal displacement of the intima‐media complex. In this experiment the longitudinal displacement of the intima‐media complex increased >200% at the highest blood pressure levels as compared to baseline. Further, shear strain within the wall increased >250%; the longitudinal displacement of the adventitial region being smaller than that of the intima‐media complex. Thus, our results indicate that adrenaline can markedly influence the longitudinal displacement of the arterial wall and the resulting shear strain, and thus shear stress, within the arterial wall. This opens up a new field within cardiovascular research, revealing a previously unknown mechanism in the circulatory system. Further studies on larger materials are needed to confirm our findings and to elucidate the underlying mechanisms and the physiological, pathophysiological and clinical implications of this phenomenon.

Different Patterns of Longitudinal Displacement of the Common Carotid Artery Wall in Healthy Humans are Stable over a Four-Month Period.

Using an in-house developed ultrasonic method, we have shown that there is distinct longitudinal multiphasic displacement of the human common carotid artery (CCA) wall during the cardiac cycle. Different subjects showed markedly different patterns of displacement. At present, it is not known if the pattern of displacement in an individual is stable over time. Therefore, in this study, we measured the longitudinal displacement of the right CCA in 10 healthy humans at two different occasions 4 months apart. The basic pattern of longitudinal displacement for an individual was highly stable, including intraclass correlation coefficient (ICC) of 0.88 for the ratio between the first antegrade and the retrograde displacement, and ICC of 0.76 for the magnitude of the first antegrade displacement. The stable basic pattern of displacement showed marked differences among subjects, also of the same age and gender. Further studies are needed to elucidate the underlying mechanisms, the physiologic, pathophysiologic and clinical implications of this phenomenon.

Cardiovascular function in adulthood following intrauterine growth restriction with abnormal fetal blood flow

To examine whether intrauterine growth restriction (IUGR) is associated with increased cardiovascular risk later in life.

Accuracy and Reproducibility of a Novel Dynamic Volume Flow Measurement Method

In clinical practice, blood volume flow (BVF) is typically calculated assuming a perfect parabolic and axisymmetric velocity distribution. This simple approach cannot account for the complex flow configurations that are produced by vessel curvatures, pulsatility and diameter changes and, therefore, results in a poor estimation. Application of the Womersley model allows compensation for the flow distortion caused by pulsatility and, with some adjustment, the effects of slight curvatures, but several problems remain unanswered. Two- and three-dimensional approaches can acquire the actual velocity field over the whole vessel section, but are typically affected by a limited temporal resolution. The multigate technique allows acquisition of the actual velocity profile over a line intersecting the vessel lumen and, when coupled with a suitable wall-tracking method, can offer the ideal trade-off among attainable accuracy, temporal resolution and required calculation power. In this article, we describe a BVF measurement method based on the multigate spectral Doppler and a B-mode edge detector algorithm for wall-position tracking. The method has been extensively tested on the research platform ULA-OP, with more than 1700 phantom measurements at flow rates between 60 and 750 mL/min, steering angles between 10 ° and 22 ° and constant, sinusoidal or pulsed flow trends. In the averaged BVF measurement, we found an underestimation of about -5% and a coefficient of variability (CV) less than 6%. In instantaneous measurements (e.g., systolic peak) the CV was in the range 2%-8.5%. These results were confirmed by a preliminary test on the common carotid artery of 10 volunteers (CV = 2%-11%).

A Method for Arterial Diameter Change Measurements Using Ultrasonic B-Mode Data.

Arterial diameter change is related to distending blood pressure and is used in estimation of arterial stiffness parameters. A common technique to track the arterial walls is by integration of wall velocities estimated by different methods using cross correlation or tissue Doppler. However, because of the high pulse repetition frequency and the need for separate pulsing sequences, the B-mode image quality is affected. We have previously developed a fast algorithm for direct measurement of lumen diameter using B-mode images. In this study we have improved the technique to be more robust and also implemented measurements of diameter change, maximum differential wall velocity and relative diameter change of the common carotid artery noninvasively in vivo. The influence of the lateral width of the region of interest (ROI; 1 pixel, 0.1 mm, 0.5 mm, 1 mm, 2.5 mm and 5 mm) was evaluated. Using the optimal lateral width (2.5 mm), the systematic and random differences between two consecutive measurements were 21 microm and 105 microm, respectively, for lumen diameter measurement; -7 microm and 39 microm, respectively, for lumen diameter change measurements; -0.2 mm/s and 0.9 mm/s, respectively, for maximum relative wall velocity; and -0.2 % and 0.8 %, respectively, for measurements of the relative diameter change. The coefficient of variation (CV) was 1.9%, 5.2%, 7.9% and 6.0%, respectively. The study indicates that the reproducibility is sufficient for in vivo studies when the width of the ROI is 1.0 mm or wider.

Frequency- and phase-sensitive magnetomotive ultrasound imaging of superparamagnetic iron oxide nanoparticles

It has recently been demonstrated that superparamagnetic iron oxide nanoparticles can be used as magnetomotive ultrasound contrast agents. A time-varying external magnetic field acts to move the particles and, thus, the nanoparticle-laden tissue. However, the difficulty of distinguishing this magnetomotive motion from undesired movement induced in regions without nanoparticles or other motion artifacts has not been well reported. Using a high-frequency linear-array system, we found that displacements outside nanoparticle-laden regions can be similar in magnitude to those in regions containing nanoparticles. We also found that the displacement outside the nanoparticle regions had a phase shift of approximately π radians relative to that in the nanoparticle regions. To suppress signals arising from undesirable movements, we developed an algorithm based on quadrature detection and phase gating at the precise frequency of nanoparticle displacement. Thus, clutter at other frequencies can be filtered out, and the processed signal can be color-coded and superimposed on the B-mode image. The median signal-to-clutter ratio improvement using the proposed algorithm was 36 dB compared with simply summing the movement energy at all frequencies. This clutter rejection is a crucial step to move magnetomotive ultrasound imaging of nanoparticles toward in vivo investigations.