The challenge of choosing in cardiovascular risk management.

Cardiovascular disease (CVD) is a major cause of morbidity and mortality worldwide. For many years guidelines have listed optimal preventive therapy. More recently, novel therapeutic options have broadened the options for state-of-the-art CV risk management (CVRM). In the majority of patients with CVD, risk lowering can be achieved by utilising standard preventive medication combined with lifestyle modifications. In a minority of patients, add-on therapies should be considered to further reduce the large residual CV risk. However, the choice of which drug combination to prescribe and in which patients has become increasingly complicated, and is dependent on both the absolute CV risk and the reason for the high risk. In this review, we discuss therapeutic decisions in CVRM, focusing on (1) the absolute CV risk of the patient and (2) the pros and cons of novel treatment options.

[Anti-inflammatory therapy in cardiovascular disease; from hypothesis to future guideline?] / Anti-inflammatoire therapie bij hart- en vaatziekten.

Atherosclerosis is a lipid-driven inflammatory disease, in which both lipids and inflammation can be considered treatment targets. The CANTOS-trial, using the IL-1ß monoclonal antibody canakinumab, has proven the concept of targeting inflammation to reduce cardiovascular risk. In contrast, the anti-inflammatory drug methotrexate failed to show cardiovascular benefit. Colchicine is a drug used in gout patients, acting as a non-selective inflammasome inhibitor. The COLCOT-trial uncovered a significant reduction in ischemic cardiovascular events in subjects following an acute myocardial infarction, which was recently confirmed in the larger LoDoCo2-trial in stable coronary heart disease. Guideline committees will have to decide whether the trials have supplied sufficient evidence to implement the routine use of colchicine in the guidelines for cardiovascular risk management. These convincing endpoint trials have paved the way for tailored treatment regimens, comprising anti-inflammatory agents besides currently established treatment modalities in CVRM.

A lethal case of the dapsone hypersensitivity syndrome involving the myocardium.

In the Netherlands dapsone is used for the treatment of dermatitis herpetiformis, leprosy and Pneumocystis jiroveci pneumonia and prophylaxis in case of cotrimoxazole allergy. An idiosyncratic drug reaction, known as the dapsone hypersensitivity syndrome (DHS), appears in about 0.5-3.6% of persons treated with dapsone. DHS can be associated with fever, rash and systemic involvement. We present a 35-year-old woman who developed severe DHS seven weeks after starting dapsone. Six weeks after being discharged in a good clinical condition she died from fulminant myocarditis, 11 weeks after the first DHS symptoms and the discontinuation of dapsone.

A new multislab 3D balanced turbo field echo technique for imaging of the renal arteries without contrast agent.

An 80-year-old female patient with arterial hypertension and slowly progressive deterioration of renal function was referred to our department for investigation of the renal arteries. Imaging of the renal arteries with ultrasound was inconclusive, due to obesity. Subsequently, imaging was performed with balanced turbo field echo which is a newly developed technique in our department. This new technique for the moment is still combined with contrast-enhanced magnetic resonance angiography. A therapeutic digital subtraction angiography was performed for stent placement.

On-line flow quantification by low-resolution phase-contrast MR imaging and model-based postprocessing.

Over the past decade, magnetic resonance (MR) imaging has been developed toward a tool for guiding and evaluating diagnostic and therapeutic interventions. Within the field of vascular MR-guided interventions, MR has potential for providing on-line monitoring of the blood volume flow rate, which is relevant during procedures such as balloon angioplasty and stent placement. We recently reported a hardware and software environment for enabling flow quantification every 8 seconds using nontriggered phase-contrast imaging. In the present study, the objective was to increase temporal resolution further to one evaluation per 4 seconds. We achieve this by lowering spatial resolution to 3 pixels per lumen diameter. The accuracy of the measurements is preserved by applying model-based postprocessing for quantification of the volume flow rate. Phantom and volunteer studies are presented, demonstrating the accuracy of the model-driven approach for the applied short acquisitions. The capabilities of the presented approach are illustrated by the results of several hypercapnia experiments and carotid compression tests performed on healthy volunteers.

MR digital subtraction angiography with asymmetric echo acquisition and complex subtraction: improved lumen and stenosis visualization.

The use of complex subtraction in dynamic thick slab 2D MR digital subtraction angiography (MR-DSA) has been shown to eliminate partial volume effects, which are present if vessels cover a small fraction of the 2D slab. However, spin dephasing still results in a poor visualization of areas with complex flow. In this paper, it is shown that this can be overcome by using asymmetric echo (ASE) acquisition combined with complex subtraction. It is proven that an ASE acquisition does not destroy information necessary for complex subtraction if the subtraction is performed in k-space. As a consequence, the subtraction reconstruction is as reliable as the magnitude reconstruction of a single ASE data set. Experiments with ASE and complex subtraction show that flow voids near stenoses disappear, that the signal-to-noise ratio is improved and that temporal resolution is increased.

MR phase-contrast flow measurement with limited spatial resolution in small vessels: value of model-based image analysis.

Magnetic resonance phase-contrast volume flow rate (VFR) measurement with limited resolution in small vessels is subject to two major sources of error: a) partial volume artifacts, causing systematic overestimation of the VFR, and b) errors related to the selection of vessel pixels [region of interest (ROI)], causing large inter-observer and intra-observer variability. Additionally, limited resolution results in Gibbs-ringing around vessels, which adversely affects VFR determination. In this paper, a semi-automatic model-based method is presented that effectively eliminates errors due to both partial volume effect and Gibbs-ringing and also minimizes errors from variability in the ROI selection. The model assumes a parabolic flow profile and cylindrical vessel geometry, incorporates inflow effects, and takes into account the point-spread function of the acquisition. The method automatically estimates maximum velocity, vessel radius, and VFR. The method is validated in phantoms under various conditions and evaluated in vivo. For small vessels with moderately pulsatile flow, it is demonstrated that accurate VFRs and diameter estimates are obtained, virtually independent of the ROI selection, even in vessels covered by just a few pixels. Compared with conventional VFR analysis, both accuracy and reproducibility improve significantly.

Construction of a protocol for measuring blood flow by two-dimensional phase-contrast MRA.

Our aim is to describe and demonstrate the steps we have found to be useful in the construction and evaluation of protocols for triggered and nontriggered measurement of blood flow by two-dimensional phase-contrast magnetic resonance angiography (MRA). To achieve this goal, we start with a survey of factors governing the accuracy (validity) and precision (repeatability) of MR flow measurements. This knowledge, combined with prior information regarding the diameter of the target vessel and the prevailing flow conditions, is then employed to define a protocol for measuring flow with negligible systematic error. In the absence of a gold standard for in vivo flow measurements, the protocol is subsequently validated for a range of flow conditions by representative phantom experiments. Precision is then calculated from the signal-to-noise ratio (SNR) of blood in the accompanying magnitude images or, less conveniently, estimated from the standard deviation of repeated measurements. The desired precision is finally achieved by adjusting the appropriate SNR parameters. All steps involved in protocol development are demonstrated for both flow-independent and flow-dependent acquisitions.

Model-based quantitation of 3-D magnetic resonance angiographic images.

Quantification of the degree of stenosis or vessel dimensions are important for diagnosis of vascular diseases and planning vascular interventions. Although diagnosis from three-dimensional (3-D) magnetic resonance angiograms (MRA's) is mainly performed on two-dimensional (2-D) maximum intensity projections, automated quantification of vascular segments directly from the 3-D dataset is desirable to provide accurate and objective measurements of the 3-D anatomy. A model-based method for quantitative 3-D MRA is proposed. Linear vessel segments are modeled with a central vessel axis curve coupled to a vessel wall surface. A novel image feature to guide the deformation of the central vessel axis is introduced. Subsequently, concepts of deformable models are combined with knowledge of the physics of the acquisition technique to accurately segment the vessel wall and compute the vessel diameter and other geometrical properties. The method is illustrated and validated on a carotid bifurcation phantom, with ground truth and medical experts as comparisons. Also, results on 3-D time-of-flight (TOF) MRA images of the carotids are shown. The approach is a promising technique to assess several geometrical vascular parameters directly on the source 3-D images, providing an objective mechanism for stenosis grading.

Limits to the accuracy of vessel diameter measurement in MR angiography.

This work addresses the fundamental limits imposed by the MRI process on the accuracy with which vessel diameters and cross-sectional areas can be derived from time-of-flight (TOF) and phase-contrast (PC) MR source images. By means of simulations and in vitro experiments, it is demonstrated that, even in the absence of flow-related artifacts, severe inaccuracies in the determination of diameters or cross-sectional areas may occur solely because of the physical process of the MR image acquisition. Resolution and intraluminal saturation have strong effects on the vessel appearance and thus on the diameter estimation error. It is shown that low resolution leads to diameter overestimation or even underestimation and that intraluminal saturation causes severe underestimation, even for relatively low flip angles. Velocity and velocity encoding do not have a major influence on lumen appearance in PC images. Accurate diameter estimations can be attained only if lumen diameters constitute at least three pixels for both TOF and PC acquisitions, provided that intraluminal saturation is suppressed or avoided. Additionally, since the constitution of TOF and PC images is dissimilar, lumina should be analyzed differently to obtain accurate diameters and cross-sectional areas.

Phase-derivative analysis in MR angiography: reduced Venc dependency and improved vessel wall detection in laminar and disturbed flow.

A problem of current MRA techniques is the inability to accurately depict the vascular anatomy, particularly in areas of disturbed flow. Various reasons, such as intravoxel phase dispersion, saturation, temporal variations, and maximum intensity projection (MIP) nonlinearity, cause a wrong delineation of vessel boundaries. A phase contrast (PC)-based postprocessing operation, the phase derivative (PhD), is introduced to detect phase fluctuations indicating flow. Two-dimensional and three-dimensional angiographic reconstruction algorithms are presented. Mathematical formulas are derived to predict the effect of sampling to flow profiles and the effect on the PhD of these profiles. Numerical, phantom, and preliminary in vivo experiments demonstrate that PhD images do not suffer from phase wraps and allow a velocity dynamic range extension only limited by a differential phase change. It is also shown that PhD MIPs produce higher signal-to-noise ratios than conventional PC angiograms and give a better impression of the anatomy of (stenotic) vessels and of their diameters for both laminar and disturbed flow.

MR-guided endovascular interventions: susceptibility-based catheter and near-real-time imaging technique.

In a 47-year-old healthy male volunteer, susceptibility-based magnetic resonance (MR) imaging was performed in the basilic vein in the right upper arm at 1.5 T. A conventional 3-F nonbraided polyethylene catheter with a 0.3-mm lumen diameter was locally impregnated with dysprosium oxide, and six ringed areas of increased susceptibility were created. passive tracking of the catheter was performed with near-real-time conventional two-dimensional gradient-echo angiography. The entire prepared part of the catheter was depicted without steering problems or complications. Passive tracking is expected to provide a valuable adjunct to active tracking for guiding endovascular interventions.

Visualization of dedicated catheters using fast scanning techniques with potential for MR-guided vascular interventions.

This paper reports the development of dedicated catheters and real-time MR scan techniques for guiding vascular interventional procedures. By way of phantom experiments, it is shown that proper modification of the magnetic properties of catheters allows their conspicuous and consistent visualization in subsecond 2D gradient echo images and phase contrast angiograms. Dynamic scan times as low as 0.5 s could be achieved by exploiting the keyhole technique and purposeful postprocessing. The temporal resolution and spatial resolution of the resultant scan protocol shows promise for adequate tracking of catheter manipulation.

Accuracy and precision of time-averaged flow as measured by nontriggered 2D phase-contrast MR angiography, a phantom evaluation.

The purpose of this study was to assess the accuracy and precision of time-averaged flow as measured by nontriggered 2D PC. Mono-, bi-, and triphasic flow patterns, modelling waveforms encountered in the human vascular system, were generated by a computer-controlled flow system. Time-averaged flow velocity was measured by conventional 2D cardiac-triggered cine PC and by nontriggered 2D PC for different settings of the excitation flip angle and the velocity sensitivity. Accuracy and precision were determined by repeating the measurements (N = 6) and comparing the results against precisely known calibration values. Measurements revealed waveform-specific deviations between triggered and nontriggered acquisitions that depended on the velocity sensitivity and, more strongly, on the flip angle of the nontriggered experiment. This confirmed the theoretically predicted predominance of amplitude over phase effects. Systematic errors could be reduced by decreasing the flip angle and the velocity sensitivity, although at the expense of signal-to-noise, so that additional signal averaging was required to maintain a specified precision. The attainable accuracy appeared to be acceptable only for waveforms with a relatively low pulsatility index. The study demonstrates the feasibility of accurate and precise nontriggered velocity measurements for weakly pulsatile flow and indicates a route towards improving the reliability for highly pulsatile flow.