Sebastian Graf

Experimental and clinical validation of arterial diameter waveform and intimal media thickness obtained from B-mode ultrasound image processing

A new automated computerized system (IôTEC) that assesses concomitantly the instantaneous temporal arterial diameter and intimal media thickness (IMT) obtained from B-mode ultrasound (US) images was validated by sonomicrometry in sheep, by an echo-tracking system in humans, and by a Lucite phantom in vitro. Differences between methods for diameter measurements did not vary in any systematic way, with no significant differences in the lower frequency range. Ultrasonic measurements of the true phantom gap sizes showed high correlation (r2 = 0.98,p < 0.001) with no systematic errors. Carotid and femoral arteries in humans were strongly related between IôTEC and echo-tracking device (r2 = 0.94 carotid; R2 = 0.88 femoral, p < 0.001), with a Gaussian distribution of the errors. This new method showed high intra- and interobserver repeatability of arterial diameter and IMT, allowing consistent characterization of arterial dynamics in humans.

Carotid Wall Viscosity Increase Is Related to Intima-Media Thickening in Hypertensive Patients

Increases in arterial wall viscosity and intima-media thickness (IMT) were found in hypertensive patients. Because smooth muscle cells are responsible for the viscous behavior of the arterial wall and they are involved in the process of thickening of the intima-media complex, this study evaluates the relationship between carotid thickness and wall viscosity. The simultaneous and noninvasive assessment of the intima-media complex and arterial diameter waveform was performed using high-resolution ultrasonography. This technique was contrasted against sonomicrometry in sheep, showing that the waveforms obtained by both methods were similar. The common carotid arteries of 11 normotensive subjects (NTA) and 11 patients with mild to moderate essential hypertension (HTA) were measured noninvasively by using tonometry and an automatic densitometric analysis of B-mode images to obtain IMT and instantaneous pressure and diameter loops. A viscoelastic model was used to derive the wall viscosity index (eta) using the hysteresis loop elimination criteria. In NTA, eta was 2.73+/-1.66 (mm Hg x s/mm) and IMT was 0.58+/-0.08 (mm), whereas in HTA, eta was 5.91+/-2.34 (P<.025) and IMT was 0.70+/-0.12 (P<.025), respectively. When all data of eta versus IMT of NTA and HTA were pooled in a linear regression analysis, a correlation coefficient of r=.71 (P<.05) was obtained. Partial correlation between eta and IMT holding constant pressure was r=.59 (P<.05). In conclusion, wall viscosity increase was associated with a higher IMT even maintaining blood pressure fixed, suggesting that the intima-media thickening might be related to smooth muscle alterations manifested as an increase in viscous behavior.

Smart Damping Modulation of Carotid Wall Energetics in Human Hypertension Effects of Angiotensin-Converting Enzyme Inhibition

Damping is the conversion of mechanical energy of a structure into thermal energy, and it is related to the material viscous behavior. To evaluate the role of damping in the common carotid artery (CCA) wall in human hypertension and the possible improvement of angiotensin-converting enzyme (ACE) inhibition, we used noninvasive CCA pressure (tonometry) and diameter (B-mode echography) waveforms in normotensive subjects (NT group; n=12) and in hypertensive patients (HT group; n=22) single-blind randomized into HT–placebo (n=10) or HT-treated (ramipril, 5 to 10 mg/d during 3 months; n=12). Vascular smooth muscle (VSM) null tonus condition was achieved from in vitro pressure and diameter waveforms (Konigsberg microtransducer and sonomicrometry) measured in explanted human CCA (n=14). Arterial wall dynamics was described by viscous (&eegr;), inertial (M), and compliance (C) parameters, mean circumferential wall stress, viscous energy dissipation (WD), peak strain energy (WSt), damping ratio (&xgr;=WD/WSt), and modeling isobaric indexes CIso and WSt(Iso). The lack of VSM tonus isobarically increased wall stress and reduced &eegr;, CIso, and damping (P<0.01). Wall stress, &eegr;, and WD were greater in HT than in NT (P<0.015) and arrived near normal in HT-treated (P<0.032 respect to HT), with no changes in HT–placebo. Whereas CIso increased in HT-treated (P<0.01) approaching the NT level, &xgr; did not vary among groups. During hypertension, because of the WSt increase, the arterial wall reacts increasing WD to maintain &xgr;. ACE inhibition modulates VSM activation and vessel wall remodeling, significantly improving wall energetics and wall stress. This protective vascular action reduces extra load to the heart and maintains enhanced arterial wall damping.

Arterial wall structure and dynamics in type 2 diabetes mellitus methodological aspects and pathophysiological findings.

Type 2 Diabetes Mellitus (DM), or adult-onset diabetes, is being considered as a new pandemic. Cardiovascular disease is the major cause of morbidity and mortality in type 2 DM, due to arterial structure and functional changes. Assessment of arterial structure and biomechanics, by non-invasive methods and parameters, can be used to detect early alterations related to DM. Three markers of vascular disease may help to a better evaluation of vascular dysfunction in type 2 DM patients: carotid intimamedia thickness (IMTc), arterial stiffness, assessed by pulse wave velocity (PWV), and endothelial function, evaluated through the brachial artery flow-mediated dilation (FMD). Among these parameters, IMTc is considered a marker of structural vessel wall properties, and arterial stiffness reflects functional wall properties. Endothelial function represents the arterial way to actively regulate its diameter (smooth muscle-dependent actions) and its visco-elastic properties (wall elasticity and viscosity). IMTc is increased in patients with type 2 DM and other independent risk factors, such as: age, hyperlipidemia and duration of DM. Subjects with DM have shown increased arterial stiffness. Type 2 DM is associated with reductions in FMD (endothelial dysfunction), which has already been reported to be inversely and strongly related to the extent of hyperglycemia. The underlying patho-physiological mechanisms are complex and remain to be fully elucidated. A complete understanding of the association between arterial alterations and early detection, and type 2 DM, may be critical for the primary prevention of DM-related macro-vascular disease.

Carotid wall inertial index increase is related to intima-media thickening in hypertensive patients

OBJECTIVE The aim of this study is to evaluate the relationship between carotid intima-media thickness (IMT) and arterial wall inertial behaviour. METHODS The simultaneous and noninvasive assessment of the intima-media complex and arterial diameter waveform was performed using high-resolution ultrasonography. The common carotid artery of eleven normotensive subjects (NTA) and eleven mild-to-moderate essential hypertensive patients (HTA) were measured noninvasively using tonometry and an automatic densitometric analysis of B-mode images to obtain IMT and instantaneous pressure (P) and diameter (D) loops. A linear discrete time model was used to estimate the inertial index (K(M)) using a system modelling-identification approach. RESULTS In NTA K(M) was 0.333+/-0.256 (mmHg x s2/mm) and IMT 0.643+/-0.061 (mm), whereas in HTA K(M) was 0.798+/-0.590 (P < 0.05) and IMT 0.760+/-0.034 (P < 0.025). When all data of K(M) versus IMT of NTA and HTA were pooled in a linear regression analysis, a correlation coefficient of r = 0.61 (P < 0.05) was obtained. CONCLUSION Wall inertia increase was associated with a higher IMT, suggesting that the intima-media thickening might be partially related to vascular hypertrophy manifested as increase of inertial behaviour.

Calcifications of the thoracic aorta on extended non-contrast-enhanced cardiac CT.

Background The presence of calcified atherosclerosis in different vascular beds has been associated with a higher risk of mortality. Thoracic aorta calcium (TAC) can be assessed from computed tomography (CT) scans, originally aimed at coronary artery calcium (CAC) assessment. CAC screening improves cardiovascular risk prediction, beyond standard risk assessment, whereas TAC performance remains controversial. However, the curvilinear portion of the thoracic aorta (TA), that includes the aortic arch, is systematically excluded from TAC analysis. We investigated the prevalence and spatial distribution of TAC all along the TA, to see how those segments that remain invisible in standard TA evaluation were affected. Methods and Results A total of 970 patients (77% men) underwent extended non-contrast cardiac CT scans including the aortic arch. An automated algorithm was designed to extract the vessel centerline and to estimate the vessel diameter in perpendicular planes. Then, calcifications were quantified using the Agatston score and associated with the corresponding thoracic aorta segment. The aortic arch and the proximal descending aorta, “invisible” in routine CAC screening, appeared as two vulnerable sites concentrating 60% of almost 11000 calcifications. The aortic arch was the most affected segment per cm length. Using the extended measurement method, TAC prevalence doubled from 31% to 64%, meaning that 52% of patients would escape detection with a standard scan. In a stratified analysis for CAC and/or TAC assessment, 111 subjects (46% women) were exclusively identified with the enlarged scan. Conclusions Calcium screening in the TA revealed that the aortic arch and the proximal descending aorta, hidden in standard TA evaluations, concentrated most of the calcifications. Middle-aged women were more prone to have calcifications in those hidden portions and became candidates for reclassification.

Vascular Accesses for Haemodialysis in the Upper Arm Cause Greater Reduction in the Carotid-Brachial Stiffness than Those in the Forearm: Study of Gender Differences

Purpose. To evaluate in chronically haemodialysed patients (CHPs), if: (1) the vascular access (VA) position (upper arm or forearm) is associated with differential changes in upper limb arterial stiffness; (2) differences in arterial stiffness exist between genders associated with the VA; (3) the vascular substitute (VS) of choice, in biomechanical terms, depends on the previous VA location and CHP gender. Methods. 38 CHPs (18 males; VA in upper arm: 18) were studied. Left and right carotid-brachial pulse wave velocity (PWVc-b) was measured. In in vitro studies, PWV was obtained in ePTFE prostheses and in several arterial and venous homografts obtained from donors. The biomechanical mismatch (BM) between CHP native vessel (NV) and VS was calculated. Results/Conclusions. PWVc-b in upper limbs with VA was lower than in the intact contralateral limbs (P < 0.05), and differences were higher (P < 0.05) when the VA was performed in the upper arm. Differences between PWVc-b in upper limbs with VA (in the upper arm) with respect to intact upper limbs were higher (P < 0.05) in males. Independently of the region in which the VA was performed, the homograft that ensured the minimal BM was the brachial artery. The BM was highly dependent on gender and the location in the upper limb in which the VA was performed.

The physiological impact of the nonlinearity of arterial elasticity in the ambulatory arterial stiffness index

The ambulatory arterial stiffness index (AASI) is claimed to be a new estimator for arterial rigidity. It was recently defined as one minus the slope of the linear regression of systolic to diastolic ambulatory pressure during 24 h. Although several reports testify its clinical relevance, the explanation of how this new index is conceptually associated with arterial stiffness remains controversial. In this work we hypothesize that nonlinear arterial elasticity is behind AASI physiological principles. To that end, random number generators were used to emulate arterial cross-sectional area (CSA) during 24 h. Pressure values were calculated using linear and nonlinear elasticity models for rigid and compliant arteries. The AASI was calculated from simulated pressures and also analytically predicted for each model. Additionally, invasive aortic pressure and CSA were continuously measured in a conscious sheep during 24 h to test the nonlinear model. We found that analytical solutions agreed with simulation outcomes; for the nonlinear model, the AASI was higher in rigid arteries with respect to compliant arteries (0.51 versus 0.38) and the linear model systematically predicted AASI = 0. For in vivo pressure measurements, AASI was 0.31. Using the measured pulsatile CSA and an estimation of the elastic constant for the nonlinear model, the AASI was accurately predicted with errors below 5%. We conclude that the AASI is higher in stiffer arteries due to the nonlinear behavior of the arterial wall. With a nonlinear arterial function, the slope of the linear regression of diastolic to systolic pressures during 24 h depends on the product of an elastic constant by the pulsatile CSA. As the elastic constant dominates the product, the reported associations between the AASI and arterial stiffness indices now have a consistent explanation.

Identifying the principal modes of variation in human thoracic aorta morphology.

Purpose: Diagnosis and management of thoracic aorta (TA) disease demand the assessment of accurate quantitative information of the aortic anatomy. We investigated the principal modes of variation in aortic 3-dimensional geometry paying particular attention to the curvilinear portion. Materials and Methods: Images were obtained from extended noncontrast multislice computed tomography scans, originally intended for coronary calcium assessment. The ascending, arch, and descending aortas of 500 asymptomatic patients (57±9 y, 81% male) were segmented using a semiautomated algorithm that sequentially inscribed circles inside the vessel cross-section. Axial planes were used for the descending aorta, whereas oblique reconstructions through a toroid path were required for the arch. Vessel centerline coordinates and the corresponding diameter values were obtained. Twelve size and shape geometric parameters were calculated to perform a principal component analysis. Results: Statistics revealed that the geometric variability of the TA was successfully explained using 3 factors that account for ∼80% of total variability. Averaged aortas were reconstructed varying each factor in 5 intervals. Analyzing the parameter loadings for each principal component, the dominant contributors were interpreted as vessel size (46%), arch unfolding (22%), and arch symmetry (12%). Variables such as age, body size, and risk factors did not substantially modify the correlation coefficients, although some particular differences were observed with sex. Conclusions: We conclude that vessel size, arch unfolding, and symmetry form the basis for characterizing the variability of TA morphology. The numerical data provided in this study as supplementary material can be exploited to accurately reconstruct the curvilinear shape of normal TAs.

Construction of a 3D coronary map to assess geometrical information in-vivo from coronary patients

Traditional risk factors are involved in the development of coronary artery disease (CAD), but geometrical risk factors have also proved to be determinant. In this work we present a new method to construct a 3D map of the left coronary artery tree using CT image processing and skeletonization techniques. We computed cumulative length-volume functions through the coronary tree bifurcations and also the relationships between total tree volumes, total length, number of segments and bifurcations with respect to the presence and severity of atherosclerotic plaques. A total of 65 patients, 40 with and 20 without CAD were recruited. We found more vascular segments and bifurcations per patient in the CAD group. Accordingly, total cumulative length was longer in CAD patients (p<0.01) whereas total cumulative volume was similar between groups. Cumulative length-volume (L-V) relationships conformed to an allometric function L = KV.V?. The allometric slope ??0.75 did not change with disease, whereas the allometric constant KV was lower in the healthy group (p<0.05) consistent with the literature. These results suggest that CAD patients follow a compensatory mechanism, dilating the vessels to maintain a normal coronary flow. The 3D coronary map offers useful quantitative information of the coronary morphometry.