Guideline treatment results in regression of atherosclerosis in type 2 diabetes mellitus.

BACKGROUND: Efficacy of guideline cardiovascular disease prevention regimens may differ between patients with or without type II diabetes mellitus. We therefore compared change in carotid artery wall dimensions in type II diabetes mellitus and non-type II diabetes mellitus patients with a history of a major cardiovascular disease event, using magnetic resonance imaging. METHODS: Thirty type II diabetes mellitus patients and 29 age- and sex-matched non-diabetes mellitus patients with a history of stroke or myocardial infarction and a carotid artery stenosis (15%-70%) were included. In all patients, treatment was according to cardiovascular risk management guidelines. At baseline and follow-up, carotid artery vessel wall dimensions were measured using 1.5 T magnetic resonance imaging. RESULTS: After 2 years of follow-up, total wall volume of the carotid artery in type II diabetes mellitus patients decreased by 9.6% (p = 0.016). In contrast, stabilization rather than regression of carotid artery wall dimensions was observed in non-diabetes mellitus patients over a 2-year period. Body mass index was identified as a predictor of total wall volume decrease. CONCLUSIONS: Guideline treatment arrests atherogenesis in non-diabetes mellitus patients and even decreases vessel wall dimensions in type II diabetes mellitus patients. Baseline body mass index predicts cardiovascular disease prevention efficacy expressed as decrease in total wall volume. These data emphasize the importance of optimal cardiovascular-prevention, particularly in diabetes patients with a high body mass index.

Diastolic carotid artery wall shear stress is associated with cerebral infarcts and periventricular white matter lesions.

BACKGROUND AND PURPOSE: Low wall shear stress (WSS) is an early marker in the development of vascular lesions. The present study aims to assess the relationship between diastolic and systolic WSS in the internal carotid artery and periventricular (PWML), deep white matter lesions, and cerebral infarcts (CI). METHODS: Early, mid, and late diastolic and peak systolic WSS were derived from shear rate obtained by gradient echo phase contrast magnetic resonance sequences multiplied by individually modeled viscosity. PWML, deep white matter lesions, and CI were derived from proton density (PD), T2, and fluid attenuated inversion recovery (FLAIR) MRI in 329 participants (70-82 years; PROSPER baseline). Analyses were adjusted, if appropriate, for age, gender, intracranial volume, and multiple cardiovascular risk factors. RESULTS: Mid-diastolic WSS was significantly correlated with the presence of PWML (B=-10.15; P=0.006) and CI (B=-2.06; P=0.044), but not with deep white matter lesions (B=-1.30; P=0.050; adjusted for age, gender, WML, and intracranial volume). After adjustment for cardiovascular risk factors, these correlations weakened but remained significant. Systolic WSS was not correlated with any of the cerebrovascular parameters. CONCLUSIONS: This study is the first to our knowledge to present a cross-sectional correlation between carotid artery WSS and cerebrovascular pathology such as PWML and CI in a large population. Furthermore, it shows that diastolic hemodynamics may be more important than systolic or mean hemodynamics. Future studies exploring vascular hemodynamic damage should focus on diastolic WSS.

Improved viscosity modeling in patients with type 2 diabetes mellitus by accounting for enhanced red blood cell aggregation tendency.

AIMS: Distorted wall shear stress (WSS) in patients with type 2 diabetes mellitus (T2DM) may be partly explained by an altered red blood cell aggregation tendency (RAT) on viscosity at low shear rate (SR). The present study evaluates viscosity modeling by implementation of hematocrit and RAT in patients with and without T2DM (non-T2DM). METHODS: A Couette viscometer and LORCA aggregometer provided viscosity and RAT on 6 shear rates in 55 patients (46-78 yrs, 66% male, T2DM: n = 28), following informed consent. Using a K-fold cross-validation, two linear mixed models predicted by SR and Hct and by SR, Hct and RAT were compared. RESULTS: In non-T2DM modeling was improved in relatively low RATs (48%, p = 1.0 x 10-11) and became worse in relatively high RATs (-18%, p = 0.019). In T2DM the opposite was observed, as modeling became worse in relatively low RATs (-16%, p = 0.001) but was improved in relatively high RATs (22%, p = 0.022). CONCLUSIONS: In addition to confirming previous research, major differences in modeling improvement between T2DM and non-T2DM were found. Especially patients with T2DM, a high RAT and often high viscosity at low SR benefit from a more accurate viscosity modeling. Further studies should evaluate how these findings affect WSS in these patients.

Diastolic wall shear stress in the internal carotid artery is associated with different cardiovascular risk factors than systolic wall shear stress.

BACKGROUND AND PURPOSE: Wall shear stress (WSS) is the frictional force exerted by the circulating blood on the endothelium. Low systolic WSS is identified as an atherosclerotic risk factor. Recently, also the importance of diastolic WSS has been described. Still, it is unknown whether diastolic WSS carries similar cardiovascular risk factors compared to systolic WSS. METHODS: Of 379 subjects (70-82 years, 56% male) diastolic and systolic WSS in the internal carotid arteries was determined. RESULTS: After adjustment for age and gender, diastolic blood pressure was associated with systolic WSS (p = 0.02). Body mass index was associated with diastolic WSS (p = 0.04). Smoking was associated with diastolic WSS (p = 0.05). Myocardial infarction was associated with both systolic WSS (p = 0.04) and diastolic WSS (p < 0.01). No associations between cholesterol, HDL, LDL, triglycerides, history of diabetes, hypertension, angina pectoris, claudication, stroke, or any vascular disease were found with systolic or diastolic WSS. CONCLUSIONS: Our data indicates different cardiovascular risk factors for diastolic WSS compared to systolic WSS.

Reproducibility of wall shear stress assessment with the paraboloid method in the internal carotid artery with velocity encoded MRI in healthy young individuals.

PURPOSE: To verify whether wall shear stress (WSS) can be assessed in a reproducible manner using automatic model-based segmentation of phase-contrast MR images by determination of flow volume and maximum flow velocity (Vmax) in cross-sections of these vessels. MATERIALS AND METHODS: The approach is based on fitting a 3D paraboloid to the actual velocity profiles and on determining Vmax. WSS was measured in the internal carotid arteries of two groups of healthy young volunteers. The reproducibility of rescanning and repositioning was studied in the first group. In the second group a 1-week and a 1-month interval was investigated. Reproducibility was calculated by the intraclass correlation (ICC). RESULTS: The flow volume, Vmax, and WSS averaged over the cardiac cycle were found to be 287.8 +/- 29.7 mL/min, 37.0 +/- 4.6 cm/s, and 1.13 +/- 0.16 Pa, respectively. The diastolic WSS varied between 1.00 +/- 0.21 Pa without averaging to 0.88 +/- 0.16 Pa with temporal and spatial averaging. Systolic WSS was 1.67 +/- 0.33 Pa without averaging and 1.67 +/- 0.25 Pa with averaging. ICC varied between 0.58 and 0.87 without averaging and between 0.75 and 0.90 with averaging for WSS. CONCLUSION: WSS in MR images of the internal carotid artery can be assessed semiautomatically with good to excellent reproducibility without inter- or intraobserver variability using model-based postprocessing.

Pravastatin decreases wall shear stress and blood velocity in the internal carotid artery without affecting flow volume: results from the PROSPER MRI study.

BACKGROUND AND PURPOSE: Despite speculations, it is unknown whether statins affect wall shear stress (WSS). Therefore, the effect of pravastatin on WSS was investigated. METHODS: In 355 elderly individuals participating in the PROSPER study (follow up after 3 years), the effect of 40 mg pravastatin on WSS was assessed in the internal carotid artery using magnetic resonance imaging. RESULTS: WSS and blood velocity decreased both in the pravastatin group and in the placebo group but decreased faster in the pravastatin group (P<0.04, P<0.02). Blood volume flow did not differ between the groups. CONCLUSIONS: In elderly subjects, the WSS and blood velocity of the internal carotid artery declines significantly over time and this decline is more pronounced in subjects treated with 40 mg pravastatin compared with the placebo group.

Lack of effect of pravastatin on cerebral blood flow or parenchymal volume loss in elderly at risk for vascular disease.

BACKGROUND AND PURPOSE: Ageing is associated with a decline in cerebral blood flow. Animal studies have shown that cholesterol-lowering therapy with statins might preserve cerebral blood flow (CBF). We examined the effect of 40 mg pravastatin on the decline in CBF and brain volume in a subset of elderly subjects participating in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) trial. METHODS: Randomization was not stratified according to whether or not subjects participated in the MRI substudy. In 391 men (n=226) and women (n=165) aged 70 to 82 years (mean+/-SD, 75+/-3.2), we measured total CBF (in mL/min) at baseline and after a mean+/-SD follow-up of 33+/-1.4 months with a gradient-echo phase-contrast MRI technique. Total CBF was defined as the summed flows in both internal carotid and vertebral arteries. Parenchymal volume (whole brain) was segmented with the use of in-house-developed semiautomatic software. RESULTS: Total CBF significantly declined in the placebo-allocated group, from 521+/-83 to 504+/-92 mL/min (P=0.0036) and in the pravastatin-allocated group from 520+/-94 to 506+/-92 mL/min (P=0.018). This decline was not significantly different between treatment groups (P=0.56). There was also a significant reduction in brain volume over time (P<0.001), which was not different between the treatment groups (P=0.47). When expressed per unit of parenchymal volume, the decline in CBF over time was no longer statistically significant. CONCLUSIONS: Elderly people at risk for cerebral vascular disease had a significant decline in CBF with increasing age that was explained by a concomitant reduction in brain volume. Treatment with 40 mg pravastatin daily had no beneficial effect on total CBF.

The influence of flow, vessel diameter, and non-newtonian blood viscosity on the wall shear stress in a carotid bifurcation model for unsteady flow.

OBJECTIVES: The atherosclerotic process in arteries is correlated with the local wall shear stress (WSS). Plaque development particularly occurs in regions with recirculation (ie, where the WSS oscillates). We investigated the effects of non-Newtonian blood viscosity, variations in flow rate, and vessel diameter on wall phenomena in a carotid bifurcation model. MATERIALS AND METHODS: The flow through a model of a carotid artery bifurcation was simulated by means of the finite element method. The whole-blood viscosity is a function of shear rate, and was modeled by the Carreau-Yasuda (CY) model. Flow rate and vessel morphology were assessed with magnetic resonance imaging. Flow rate, blood viscosity, and hematocrit levels (Hct) were measured in 49 healthy volunteers. We propose an adaptation of the CY model so that differences in Hct can be incorporated; furthermore, plasma viscosity was varied in the CY model. RESULTS: The data from our model indicate that flow increases have a larger effect on the WSS than predicted with a simple paraboloid model. Hct had more influence on the WSS when the plasma viscosity was low. Low plasma viscosity was associated with a low WSS, which implies a contradiction, because both high WSS and low plasma viscosity are thought to be indicators for a healthy system. Maximum WSS oscillations were found at the edges of the recirculation region. CONCLUSIONS: Flow and diameter changes have significant influence on wall shear stress values; the same is true for the viscosity, but to a lesser extent.

Automatic model-based contour detection and blood flow quantification in small vessels with velocity encoded magnetic resonance imaging.

RATIONALE AND OBJECTIVES: The quantitative assessment of blood flow in peripheral vessels from phase-contrast magnetic resonance imaging studies requires the accurate delineation of vessel contours in cross-sectional magnetic resonance images. The conventional manual segmentation approach is tedious, time-consuming, and leads to significant inter- and intraobserver variabilities. The aim of this study was to verify whether automatic model-based segmentation decreases these problems by fitting a model to the actual blood velocity profile. METHODS: In this study 2 new fully automatic methods (a static and a dynamic approach) were developed and compared with manual analyzes using phantom and in vivo studies of internal carotid and vertebral arteries in healthy volunteers. The automatic segmentation approaches were based on fitting a 3D parabolic velocity model to the actual velocity profiles. In the static method, the velocity profiles were averaged over the complete cardiac cycle, whereas the dynamic method takes into account the velocity data of each cardiac time bin individually. Materials consisted of the magnetic resonance imaging data from 3 straight phantom tubes and the blood velocity profiles of 8 volunteers. RESULTS: For the phantom studies, the automatic dynamic approach performed significantly better than the manual analysis (intraclass correlations [ICC] of 0.62-0.98 and 0.30-0.86, respectively). For the assessment of the total cerebral blood flow in the in vivo studies, the automatic static method performed significantly better than the manual 1 (ICC of 0.98-0.98 and 0.93-0.95, respectively). However, the automatic dynamic method was not significantly better than the manual 1 (ICC = 0.92-0.96) but had the advantage of providing additional parameters. CONCLUSION: Blood flow in magnetic resonance images of small vessels can be assessed accurately, rapidly, and fully automatically using model-based postprocessing by fitting a first approximation of the velocity profile to the actual flow data.

Reproducibility of total cerebral blood flow measurements using phase contrast magnetic resonance imaging.

PURPOSE: To evaluate reproducibility of total cerebral blood flow (CBF) measurements with phase contrast magnetic resonance imaging (pcMRI). MATERIALS AND METHODS: We repeated total CBF measurements in 15 healthy volunteers with and without cardiac triggering, and with and without repositioning. In eight volunteers measurements were performed at two different occasions. In addition, measurement of flow in a phantom was performed to validate MR measurements. RESULTS: A difference of 40.4 ml/minute was found between CBF measurements performed with and without triggering (P < 0.05). For repeated triggered measurements, the coefficient of variation (CV) was 7.1%, and for nontriggered measurements 10.3%. For repeated measurements with repositioning, the CV was 7.1% with and 11.2% without triggering. Repeated measurements at different occasions showed a CV of 8.8%. Comparing measured with real flow in the phantom, the triggered differed 4.9% and the nontriggered 8.3%. CONCLUSION: The findings of this study demonstrate that pcMRI is a reliable method to measure total CBF in terms of both accuracy and reproducibility.