Frieke M.A. Box

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

To evaluate reproducibility of total cerebral blood flow (CBF) measurements with phase contrast magnetic resonance imaging (pcMRI).

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.

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

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.

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.

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.

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.

Carotid and Basilar Artery Wall Shear Stress in Alzheimer’s Disease and Mild Cognitive Impairment

Background/Aims: Vascular pathology is increasingly seen as a factor contributing to the development of Alzheimer’s disease (AD). With this in mind we hypothesized that this vascular pathology could be directly detected in the arteries contributing to the cerebral circulation of mild cognitive impairment (MCI) and AD patients by means of wall shear stress (WSS) measurements. Methods: In this study we investigated the mean wall shear stress (MWSS), diastolic wall shear stress (DWSS) and systolic wall shear stress (SWSS) in the carotid and basilar arteries of control subjects (mean age: 72; SD: 8.8), patients suffering from MCI (mean age: 76; SD: 6.7), and patients suffering from AD (mean age: 72; SD: 8.2) that were consecutively referred to our outpatient memory clinic using in-house developed software on gradient echo phase-contrast MRI sequences. Results: We found that all these parameters were significantly lower in the carotid arteries of patients suffering from AD or MCI when compared to control subjects. In the basilar artery only DWSS was lower in MCI or AD patients compared to control subjects. In none of the arteries a difference was found for any WSS parameter between MCI and AD patients. WSS parameters were significantly associated (corrected for age and sex) with the degree of cognitive impairment. Conclusion: Increased vascular pathology, as expressed by lower WSS measures, was found in patients suffering from MCI and AD compared to normal controls. This might point to the involvement of vascular pathology in the development of AD.

Quantitative Methods for Comparisons between Velocity Encoded MR-Measurements and Finite Element Modeling in Phantom Models

Wall Shear Stress is a key factor in the development of atherosclerosis. To assess the WSS in-vivo, velocity encoded MRI is combined with geometry measurements by 3D MR-Angiography (MRA) and with blood flow calculations using the Finite Element Method (FEM). The 3D geometry extracted from the MRA data was converted to a mesh suitable for FEM calculations. Aiming at in-vivo studies the goal of this study was to quantify the differences between FEM calculations and MRI measurements. Two phantoms, a curved tube and a carotid bifurcation model were used. The geometry and the time-dependent flow-rate (measured by MRI) formed input for the FEM calculations. For good data quality, 2D velocity profiles were analyzed further by the Kolmogorov-Smirnov method. For the curved tube calculations and measurements matched well (prob?S approximately above 0.20). The carotid needs further investigation in segmentation and simulation to obtain similar results. It can be concluded that the error-analysis performs reliably.

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.