Coronary artery calcium scoring: an evidence-based guide for primary care physicians.

Primary care physicians often must decide whether statin therapy would be appropriate (in addition to lifestyle modification) for managing asymptomatic individuals with borderline or intermediate risk for developing atherosclerotic cardiovascular disease (ASCVD), as assessed on the basis of traditional risk factors. In appropriate subjects, a simple, noninvasive measurement of coronary artery calcium can help clarify risk. Coronary atherosclerosis is a chronic inflammatory disease, with atherosclerotic plaque formation involving intimal inflammation and repeated cycles of erosion and fibrosis, healing and calcification. Atherosclerotic plaque formation represents the prognostic link between risk factors and future clinical events. The presence of coronary artery calcification is almost exclusively an indication of coronary artery disease, except in certain metabolic conditions. Coronary artery calcification can be detected and quantified in a matter of seconds by noncontrast electrocardiogram-gated low-dose X-ray computed tomography (coronary artery calcium scoring [CACS]). Since the publication of the seminal work by Dr. Arthur Agatston in 1990, a wealth of CACS-based prognostic data has been reported. In addition, recent guidelines from various professional societies conclude that CACS may be considered as a tool for reclassifying risk for atherosclerotic cardiovascular disease in patients otherwise assessed to have intermediate risk, so as to more accurately inform decisions about possible statin therapy in addition to lifestyle modification as primary preventive therapy. In this review, we provide an overview of CACS, from acquisition to interpretation, and summarize the scientific evidence for and the appropriate use of CACS as put forth in current clinical guidelines.

Exenatide decreases hepatic fibroblast growth factor 21 resistance in non-alcoholic fatty liver disease in a mouse model of obesity and in a randomised controlled trial.

AIMS/HYPOTHESIS: Systemic fibroblast growth factor (FGF)21 levels and hepatic FGF21 production are increased in non-alcoholic fatty liver disease patients, suggesting FGF21 resistance. We examined the effects of exenatide on FGF21 in patients with type 2 diabetes and in a diet-induced mouse model of obesity (DIO). METHODS: Type 2 diabetes mellitus patients (n = 24) on diet and/or metformin were randomised (using a table of random numbers) to receive additional treatment consisting of pioglitazone 45 mg/day or combined therapy with pioglitazone (45 mg/day) and exenatide (10 µg twice daily) for 12 months in an open label parallel study at the Baylor Clinic. RESULTS: Twenty-one patients completed the entire study and were included in the analysis. Pioglitazone treatment (n = 10) reduced hepatic fat as assessed by magnetic resonance spectroscopy, despite a significant increase in body weight (Δ = 3.7 kg); plasma FGF21 levels did not change (1.9 ± 0.6 to 2.2 ± 0.6 ng/ml [mean ± SEM]). However, combined pioglitazone and exenatide therapy (n = 11) was associated with a significant reduction of FGF21 levels (2.3 ± 0.5 to 1.1 ± 0.3 ng/ml) and a greater decrease in hepatic fat. Besides weight gain observed in the pioglitazone-treated patients, lower extremity oedema was observed as a side effect in two of the ten patients. Three patients who received pioglitazone and exenatide combination therapy complained of significant nausea that was self-limiting and did not require them to leave the study. In DIO mice, exendin-4 for 4 weeks significantly reduced hepatic triacylglycerol content, decreased hepatic FGF21 protein and mRNA, and enhanced phosphorylation of hepatic AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase, although no significant difference in weight and body fat was observed. Hepatic FGF21 correlated inversely with hepatic AMPK phosphorylation CONCLUSIONS/INTERPRETATION: In type 2 diabetes mellitus, combined pioglitazone and exenatide therapy is associated with a reduction in plasma FGF21 levels, as well as a greater decrease in hepatic fat than that achieved with pioglitazone therapy. In DIO mice, exendin-4 treatment reduces hepatic triacylglycerol and FGF21 protein, and enhances hepatic AMPK phosphorylation, suggesting an improvement of hepatic FGF21 resistance. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT 01432405.

Non-contrast computed tomography is comparable to contrast-enhanced computed tomography for aortic volume analysis after endovascular abdominal aortic aneurysm repair.

OBJECTIVES: To evaluate whether non-contrast computed tomography (NCCT) images are as reliable as contrast-enhanced computed tomography (CECT) images for the measurement of aortic volume (AV). MATERIALS AND METHODS: A total of 316 pairs of AVs were retrospectively measured from 316 consecutive patients, who underwent endovascular aneurysm repair (EVAR). A standardised multidetector computed tomography protocol was used to obtain precontrast, arterial and delay-phase images. A single blinded, experienced observer measured the AV from the lowest renal artery to the aortic bifurcation by means of the disc-summation method, using the precontrast and arterial-phase images. A second blinded observer measured the AV again in 16 randomly chosen cases. RESULTS: Both NCCT and CECT yielded similar AVs that were highly correlated (r(2) = 0.99; P < 0.0001). Bland and Altman analysis revealed a small bias (mean ± 2 standard deviations: -0.9 ± 8 ml). The intraclass correlation coefficients (all >0.99; P < 0.0001) and low repeatability coefficients indicated that the AVs were reproducible with both methods. CONCLUSIONS: The AVs measured from NCCT images were accurate and highly reproducible compared with those from CECT images. Therefore, NCCT can be a reasonable alternative to CECT for AV assessment after EVAR. This is particularly important for patients with renal insufficiency (potentially sparing them from nephrotoxic contrast agents and unnecessary radiation) or allergy to contrast agents.

Direct comparison of sensitivity encoding (SENSE) accelerated and conventional 3D contrast enhanced magnetic resonance angiography (CE-MRA) of renal arteries: effect of increasing spatial resolution.

PURPOSE: To assess the effect of attaining higher spatial resolution in contrast-enhanced magnetic resonance angiography (MRA) of renal arteries using parallel imaging, sensitivity encoding (SENSE), by comparing the SENSE contrast-enhanced (CE) MRA against a conventional CE-MRA protocol with identical scan times, injection protocol, and other acquisition parameters. MATERIALS AND METHODS: Numerical simulations and a direct comparison of SENSE-accelerated versus conventional acquisitions were performed. A total of 41 patients (18 male) were imaged using both protocols for a direct comparison. Both protocols used fluoroscopic triggering, centric encoding, breath-holding, equivalent injection protocol, and lasted approximately 30 seconds. RESULTS: Simulated point-spread functions were narrower for the SENSE protocol compared to the conventional protocol. In the patient study, although the SENSE protocol produced images with lower signal-to-noise ratio (SNR), image quality was better for all segments of the renal arteries. In addition, ringing of kidney parenchyma and renal artery blurring were significantly reduced in the SENSE protocol. Finally, reader confidence improved with the SENSE protocol. CONCLUSION: Despite a reduction in SNR, the higher-resolution SENSE CE-MRA provided improved image quality, reduced artifacts, and increased reader confidence compared to the conventional protocol.

The utility of delayed-enhancement magnetic resonance imaging for identifying nonischemic myocardial fibrosis in asymptomatic patients with biopsy-proven systemic sarcoidosis.

BACKGROUND: The pathophysiology of sarcoidosis includes infiltrative inflammatory injury, as well as interstitial fibrosis formation. Delayed-enhancement (DE) magnetic resonance imaging (MRI) techniques have been shown to identify fibrotic tissue as areas of hyperenhancement. To test the hypothesis that DE-MRI can be used to identify myocardial fibrosis resulting from cardiac sarcoidosis, we assessed this method in asymptomatic patients with biopsy-proven systemic sarcoidosis. METHODS: Thirty-one patients with biopsy-confirmed systemic sarcoidosis and no known history of heart disease or sarcoid cardiac involvement underwent DE-MRI after gadolinium-chelate administration. The location and extent of DE were quantified by 2 radiologists experienced at evaluating cardiovascular MRI images. RESULTS: According to DE-MRI, 8 (26%) of the 31 patients had nonischemic fibrosis, as evidenced by abnormal DE patterns. Unlike characteristic ischemic injuries, most of the fibrosis was mid-myocardial, extending to the adjacent endocardium, epicardium, or both. The most frequent site of fibrosis was the basal inferoseptum, followed by the basal inferolateral wall. CONCLUSIONS: In asymptomatic patients with systemic sarcoidosis, DE-MRI may provide a novel, noninvasive method for the early identification of myocardial fibrosis.

Safety of gadoversetamide in patients with acute and chronic myocardial infarction.

PURPOSE: To assess the safety data from two large, multicenter, phase 2 trials on the use of gadoversetamide (OptiMARK, Tyco Healthcare/Mallinckrodt, St. Louis, MO) as a contrast agent in delayed hyperenhancement magnetic resonance imaging (DE-MRI) in patients with acute and chronic myocardial infarction (MI). MATERIALS AND METHODS: The study population from both trials comprised 577 patients who were randomly assigned to one of four dose groups (0.05, 0.1, 0.2, or 0.3 mmol/kg) before undergoing DE-MRI. Safety evaluations included physical and electrocardiographic (ECG) examinations. Vital signs, laboratory values, adverse events (AE), and serious adverse events (SAE) were monitored before and after contrast administration. RESULTS: Of the 577 patients who received gadoversetamide, 124 (21.5%) reported a total of 164 AEs; most were mild (139 AEs; 84.8%) or moderate (25 AEs; 15.2%). ECG-related changes were the most frequent AE. Site investigators judged only eight AEs as likely related to gadoversetamide and only two of the eight as clinically relevant. Further evaluation suggested neither AE was related to gadoversetamide. Two SAEs were reported, but none was judged related to gadoversetamide by the site investigators. CONCLUSION: Gadoversetamide is safe for use in patients with acute or chronic MI up to a dose of 0.3 mmol/kg.

FLAIR histogram segmentation for measurement of leukoaraiosis volume.

The purposes of this study were to develop a method to measure brain and white matter hyperintensity (leukoaraiosis) volume that is based on the segmentation of the intensity histogram of fluid-attenuated inversion recovery (FLAIR) images and to assess the accuracy and reproducibility of the method. Whole-head synthetic image phantoms with manually introduced leukoaraiosis lesions of varying severity were constructed. These synthetic image phantom sets incorporated image contrast and anatomic features that mimicked leukoaraiosis found in real life. One set of synthetic image phantoms was used to develop the segmentation algorithm (FLAIR-histoseg). A second set was used to measure its accuracy. Test retest reproducibility was assessed in 10 elderly volunteers who were imaged twice. The mean absolute error of the FLAIR-histoseg method was 6.6% for measurement of leukoaraiosis volume and 1.4% for brain volume. The mean test retest coefficient of variation was 1.4% for leukoaraiosis volume and 0.3% for brain volume. We conclude that the FLAIR-histoseg method is an accurate and reproducible method for measuring leukoaraiosis and whole-brain volume in elderly subjects.

Magnetic resonance elastography of skeletal muscle.

While the contractile properties of skeletal muscle have been studied extensively, relatively little is known about the elastic properties of muscle in vivo. Magnetic resonance elastography (MRE) is a phase contrast-based method for observing shear waves propagating in a material to determine its stiffness. In this work, MRE is applied to skeletal muscle under load to quantify the change in stiffness with loading. A mathematical model of muscle is developed that predicts a linear relationship between shear stiffness and muscle load. The MRE technique was applied to bovine muscle specimens (N = 10) and human biceps brachii in vivo (N = 5). Muscle stiffness increased linearly for both passive tension (14.5 +/- 1.77 kPa/kg) and active tension, in which the increase in stiffness was dependent upon muscle size, as predicted by the model. A means of noninvasively assessing the viscoelastic pro-perties of skeletal muscle in vivo may provide a useful method for studying muscle biomechanics in health and disease.

Diffusion-weighted MR imaging of the normal human spinal cord in vivo.

BACKGROUND AND PURPOSE: Diffusion-weighted imaging is a robust technique for evaluation of a variety of neurologic diseases affecting the brain, and might also have applications in the spinal cord. The purpose of this study was to determine the feasibility of obtaining in vivo diffusion-weighted images of the human spinal cord, to calculate normal apparent diffusion coefficient (ADC) values, and to assess cord anisotropy. METHODS: Fifteen healthy volunteers were imaged using a multi-shot, navigator-corrected, spin-echo, echo-planar pulse sequence. Axial images of the cervical spinal cord were obtained with diffusion gradients applied along three orthogonal axes (6 b values each), and ADC values were calculated for white and gray matter. RESULTS: With the diffusion gradients perpendicular to the orientation of the white matter tracts, spinal cord white matter was hyperintense to central gray matter at all b values. This was also the case at low b values with the diffusion gradients parallel to the white matter tracts; however, at higher b values, the relative signal intensity of gray and white matter reversed. With the diffusion gradients perpendicular to spinal cord, mean ADC values ranged from 0.40 to 0.57 x 10(-3) mm2/s for white and gray matter. With the diffusion gradients parallel to the white matter tracts, calculated ADC values were significantly higher. There was a statistically significant difference between the ADCs of white versus gray matter with all three gradient directions. Strong diffusional anisotropy was observed in spinal cord white matter. CONCLUSION: Small field-of-view diffusion-weighted images of the human spinal cord can be acquired in vivo with reasonable scan times. Diffusion within spinal cord white matter is highly anisotropic.

Acoustic shear-wave imaging using echo ultrasound compared to magnetic resonance elastography.

We compare a previously developed phase contrast-based magnetic resonance imaging technique (MRE) to a phase-based ultrasound (US) method for measuring small cyclic displacements (submicrometer level) caused by propagating acoustic shear waves in tissue-like media. Our preliminary experiments with gelatin phantoms show that acoustic shear-wave propagation can be measured with US, and we speculate that this technique could find applications in medical imaging.

Segmented spin-echo pulses to increase fMRI signal: repeated intrinsic diffusional enhancement.

Since its inception, functional magnetic resonance imaging (fMRI) has seen rapid progress in the application to neuroscience. Common gradient-recalled acquisition methods are susceptible to static field inhomogeneities, resulting in signal loss at the medial temporal area important for memory function or at the basal ganglia area for motor control. In addition, they are susceptible to the contaminating signals of large vein origin, such as the signals from its surrounding cerebrospinal fluid (CSF) leading to false-positive activation. Spin echoes overcome these drawbacks. However, they are less sensitive to blood oxygenation level dependent (BOLD) susceptibility changes because of their refocusing mechanism. A method is presented here to enhance the spin-echo fMRI signal by recruiting more spins to participate in the dynamic BOLD process. This method divided a conventional T(2) weighting period into several segments separated by blocks of extra free diffusion time. Before the extra diffusion time spins are restored to the longitudinal axis preventing rapid transverse relaxation. This process allows more spin access to the regions that experience the BOLD field gradient. Because of the increased spin population that is modulated by the capillary BOLD field gradient, the functional signal is increased. Spin-echo echo-planar imaging (EPI) with this enhancement may be a useful technique for fMRI studies at inhomogeneous areas such as the air/tissue interface. Magn Reson Med 42:631-635, 1999.

An orthogonal correlation algorithm for ghost reduction in MRI.

Ghosting in MRI due to modulation of k-space data can be caused by motion of the subject or characteristics of the sequence. A general solution for 2DFT MRI that reduces ghosting without causal modeling is presented. Separate image data sets are acquired in which the phase and frequency directions are swapped. In these two data sets, the image signal is correlated, whereas the ghost signals are not. By taking a correlation of these two data sets, an image with greatly reduced ghosting is obtained. The reduction is shown to depend both on the correct signal intensity of the image, as well as the ghost intensity in the ghosted region. The reduction approaches 100% in regions of low image signal, and is more moderate in regions of higher image signal. The process was applied to conventional spin-echo, fast-spin-echo, and gradient echo imaging of volunteers and a phantom. Results of a reader study of the volunteer images reflected a significant overall reduction of ghosting artifacts in all volunteer experiments.

Magnetic resonance imaging of transverse acoustic strain waves.

We describe a phase contrast based MRI technique with high sensitivity to cyclic displacement that is capable of quantitatively imaging acoustic strain waves in tissue-like materials. A formalism for considering gradient waveforms as basis functions to measure arbitrary cyclic motion waveforms is introduced. Experiments with tissue-like agarose gel phantoms show that it is possible to measure small cyclic displacements at a submicron level by an appropriate choice of the applied gradient basis function and to use this capability to observe the spatial and temporal pattern of displacements caused by acoustic strain waves. The propagation characteristics of strain waves are determined by the mechanical properties of the media. It is therefore possible to use this technique to noninvasively estimate material properties such as elastic modulus.

Magnetic resonance elastography by direct visualization of propagating acoustic strain waves.

A nuclear magnetic resonance imaging (MRI) method is presented for quantitatively mapping the physical response of a material to harmonic mechanical excitation. The resulting images allow calculation of regional mechanical properties. Measurements of shear modulus obtained with the MRI technique in gel materials correlate with independent measurements of static shear modulus. The results indicate that displacement patterns corresponding to cyclic displacements smaller than 200 nanometers can be measured. The findings suggest the feasibility of a medical imaging technique for delineating elasticity and other mechanical properties of tissue.