Noninvasive coronary vessel wall and plaque imaging with magnetic resonance imaging.

BACKGROUND: Conventional x-ray angiography frequently underestimates the true burden of atherosclerosis. Although intravascular ultrasound allows for imaging of coronary plaque, this invasive technique is inappropriate for screening or serial examinations. We therefore sought to develop a noninvasive free-breathing MR technique for coronary vessel wall imaging. We hypothesized that such an approach would allow for in vivo imaging of coronary atherosclerosis. METHODS AND RESULTS: Ten subjects, including 5 healthy adult volunteers (aged 35+/-17 years, range 19 to 56 years) and 5 patients (aged 60+/-4 years, range 56 to 66 years) with x-ray-confirmed coronary artery disease (CAD), were studied with a T2-weighted, dual-inversion, fast spin-echo MR sequence. Multiple adjacent 5-mm cross-sectional images of the proximal right coronary artery were obtained with an in-plane resolution of 0.5x1.0 mm. A right hemidiaphragmatic navigator was used to facilitate free-breathing MR acquisition. Coronary vessel wall images were readily acquired in all subjects. Both coronary vessel wall thickness (1.5+/-0.2 versus 1.0+/-0.2 mm) and wall area (21.2+/-3.1 versus 13.7+/-4.2 mm(2)) were greater in patients with CAD (both P:<0.02 versus healthy adults). CONCLUSIONS: In vivo free-breathing coronary vessel wall and plaque imaging with MR has been successfully implemented in humans. Coronary wall thickness and wall area were significantly greater in patients with angiographic CAD. The presented technique may have potential applications in patients with known or suspected atherosclerotic CAD or for serial evaluation after pharmacological intervention.

Congenital tumors: imaging when life just begins.

BACKGROUND: The technical developments of imaging methods over the last 2 decades are changing our knowledge of perinatal oncology. Fetal ultrasound is usually the first imaging method used and thus constitutes the reference prenatal study, but MRI seems to be an excellent complementary method for evaluating the fetus. The widespread use of both techniques has increased the diagnosis rates of congenital tumors. During pregnancy and after birth, an accurate knowledge of the possibilities and limits of the different imaging techniques available would improve the information obtainable, thus helping the medical team to make the most appropriate decisions about therapy and to inform the family about the prognosis. CONCLUSION: In this review article, we describe the main congenital neoplasms, their prognosis and their imaging characteristics with the different pre- and postnatal imaging methods available.

Imaging of the unstable plaque: how far have we got?

Rupture of unstable plaques may lead to myocardial infarction or stroke and is the leading cause of morbidity and mortality in western countries. Thus, there is a clear need for identifying these vulnerable plaques before the rupture occurs. Atherosclerotic plaques are a challenging imaging target as they are small and move rapidly, especially in the coronary tree. Many of the currently available imaging tools for clinical use still provide minimal information about the biological characteristics of plaques, because they are limited with respect to spatial and temporal resolution. Moreover, many of these imaging tools are invasive. The new generation of imaging modalities such as magnetic resonance imaging, nuclear imaging such as positron emission tomography and single photon emission computed tomography, computed tomography, fluorescence imaging, intravascular ultrasound, and optical coherence tomography offer opportunities to overcome some of these limitations. This review discusses the potential of these techniques for imaging the unstable plaque.

The Acute STroke Registry and Analysis of Lausanne (ASTRAL): design and baseline analysis of an ischemic stroke registry including acute multimodal imaging.

BACKGROUND AND PURPOSE: Stroke registries are valuable tools for obtaining information about stroke epidemiology and management. The Acute STroke Registry and Analysis of Lausanne (ASTRAL) prospectively collects epidemiological, clinical, laboratory and multimodal brain imaging data of acute ischemic stroke patients in the Centre Hospitalier Universitaire Vaudois (CHUV). Here, we provide design and methods used to create ASTRAL and present baseline data of our patients (2003 to 2008). METHODS: All consecutive patients admitted to CHUV between January 1, 2003 and December 31, 2008 with acute ischemic stroke within 24 hours of symptom onset were included in ASTRAL. Patients arriving beyond 24 hours, with transient ischemic attack, intracerebral hemorrhage, subarachnoidal hemorrhage, or cerebral sinus venous thrombosis, were excluded. Recurrent ischemic strokes were registered as new events. RESULTS: Between 2003 and 2008, 1633 patients and 1742 events were registered in ASTRAL. There was a preponderance of males, even in the elderly. Cardioembolic stroke was the most frequent type of stroke. Most strokes were of minor severity (National Institute of Health Stroke Scale [NIHSS] score ≤ 4 in 40.8% of patients). Cardioembolic stroke and dissections presented with the most severe clinical picture. There was a significant number of patients with unknown onset stroke, including wake-up stroke (n=568, 33.1%). Median time from last-well time to hospital arrival was 142 minutes for known onset and 759 minutes for unknown-onset stroke. The rate of intravenous or intraarterial thrombolysis between 2003 and 2008 increased from 10.8% to 20.8% in patients admitted within 24 hours of last-well time. Acute brain imaging was performed in 1695 patients (97.3%) within 24 hours. In 1358 patients (78%) who underwent acute computed tomography angiography, 717 patients (52.8%) had significant abnormalities. Of the 1068 supratentorial stroke patients who underwent acute perfusion computed tomography (61.3%), focal hypoperfusion was demonstrated in 786 patients (73.6%). CONCLUSIONS: This hospital-based prospective registry of consecutive acute ischemic strokes incorporates demographic, clinical, metabolic, acute perfusion, and arterial imaging. It is characterized by a high proportion of minor and unknown-onset strokes, short onset-to-admission time for known-onset patients, rapidly increasing thrombolysis rates, and significant vascular and perfusion imaging abnormalities in the majority of patients.

The use of contrast-enhanced MRI angiography for planning interventional catheterization

Background: Interventional catheterization is being increasingly used for relief of residual lesions in congenital heart disease. Exact anatomical imaging is crucial in the planning of an intervention. This can be provided non-invasively and without radiation by contrast-enhanced MR angiography (CEMRA). Aim: To evaluate the accuracy of the measurements of the vessels obtained by CEMRA in comparison to those obtained by conventional X-ray angiography (CXA). Methods: Retrospective blinded measurement of the diameters of aorta and pulmonary arteries on the CEMRA and CXA images, in the same locations. Comparison of the results by Pearson correlation and by calculating the limits of agreement. Results: Twenty-one children with congenital heart disease, mean age 5.6 +- 5.2 years, weight 21.1 +- 18.4 kg, underwent CEMRA and catheterization for assessment or treatment of a residual lesion. The time interval between the CEMRA and the CXA examination was 2.6 +- 2.3 months. A total of 98 measurements, 37 of the aorta and 61 of the pulmonary arteries were performed on the images obtained by each technique. The correlation between CEMRA and CXA measurements was excellent, r = 0.97, p < 0.0001. The mean difference between the two techniques was 0.018 +- 1.1mm; the limits of agreement were -2.14 and +2.18mm. Similar agreement was found for measures of the aorta (r +- 0.97, mean difference 0.20 = 1.08 mm) and of the pulmonary arteries (r +- 0.97, mean difference 0.048 = 0.89 mm). Conclusions: CEMRA provide accurate quantitative anatomical information, which highly agrees with CXA data, and can therefore be used for planning interventional catheterization.

Coronary MR angiography clinical applications and potential for imaging coronary artery disease.

Over the past decade, CMRA has emerged as a unique clinical imaging tool with applications in selected populations. Patients with suspected coronary artery anomalies and patients with Kawasaki disease and coronary aneurysms are among those for whom CMRA has demonstrated clinical usefulness. For assessment of patients with atherosclerotic CAD, CMRA is useful for detection of patency of bypass grafts. At centers with appropriate expertise and resources, CMRA also appears to be of value for exclusion of severe proximal multivessel CAD in selected patients. Data from multicenter trials will continue to define the clinical role of CMRA, particularly as it relates to assessment of CAD. Future developments and enhancements of CMRA promise better lumen and coronary artery wall imaging. This may become the new target in noninvasive evaluation of CAD.

Postmortem imaging of sudden cardiac death

Postmortem imaging is increasingly used in forensic practice in cases of natural deaths related to cardiovascular diseases, which represent the most common causes of death in developed countries. While radiological examination is generally considered to be a good complement for conventional autopsy, it was thought to have limited application in cardiovascular pathology. At present, multidetector computed tomography (MDCT), CT angiography, and cardiac magnetic resonance imaging (MRI) are used in postmortem radiological investigation of cardiovascular pathologies. This review presents the actual state of postmortem imaging for cardiovascular pathologies in cases of sudden cardiac death (SCD), taking into consideration both the advantages and limitations. The radiological evaluation of ischemic heart disease (IHD), the most frequent cause of SCD in the general population of industrialized countries, includes the examination of the coronary arteries and myocardium. Postmortem CT angiography (PMCTA) is very useful for the detection of stenoses and occlusions of coronary arteries but less so for the identification of ischemic myocardium. MRI is the method of choice for the radiological investigation of the myocardium in clinical practice, but its accessibility and application are still limited in postmortem practice. There are very few reports implicating postmortem radiology in the investigation of other causes of SCD, such as cardiomyopathies, coronary artery abnormalities, and valvular pathologies. Cardiomyopathies representing the most frequent cause of SCD in young athletes cannot be diagnosed by echocardiography, the most widely available technique in clinical practice for the functional evaluation of the heart and the detection of cardiomyopathies. PMCTA and MRI have the potential to detect advanced stages of diseases when morphological substrate is present, but these methods have yet to be sufficiently validated for postmortem cases. Genetically determined channelopathies cannot be detected radiologically. This review underlines the need to establish the role of postmortem radiology in the diagnosis of SCD.

A quantitative analysis of antagonism and inverse agonism at wild-type and constitutively active hamster alpha1B-adrenoceptors.

In order to characterize inverse agonism at alpha1B-adrenoceptors, we have compared the concentration-response relationships of several quinazoline and non-quinazoline alpha1-adrenoceptor antagonists at cloned hamster wild-type (WT) alpha1B-adrenoceptors and a constitutively active mutant (CAM) thereof upon stable expression in Rat-1 fibroblasts. Receptor activation or inhibition thereof was assessed as [3H]inositol phosphate (IP) accumulation. Quinazoline (alfuzosin, doxazosin, prazosin, terazosin) and non-quinazoline alpha1-adrenoceptor antagonists (BE 2254, SB 216,469, tamsulosin) concentration-dependently inhibited phenylephrine-stimulated IP formation at both WT and CAM with Ki values similar to those previously found in radioligand binding studies. At CAM in the absence of phenylephrine, the quinazolines produced concentration-dependent inhibition of basal IP formation; the maximum inhibition was approximately 55%, and the corresponding EC50 values were slightly smaller than the Ki values. In contrast, BE 2254 produced much less inhibition of basal IP formation, SB 216,469 was close to being a neutral antagonist, and tamsulosin even weakly stimulated IP formation. The inhibitory effects of the quinazolines and BE 2254 as well as the stimulatory effect of tamsulosin were equally blocked by SB 216,469 at CAM. At WT in the absence of phenylephrine, tamsulosin did not cause significant stimulation and none of the other compounds caused significant inhibition of basal IP formation. We conclude that alpha1-adrenoceptor antagonsits with a quinazoline structure exhibit greater efficacy as inverse agonists than those without.

Robust T1-Weighted Structural Brain Imaging and Morphometry at 7T Using MP2RAGE.

PURPOSE: To suppress the noise, by sacrificing some of the signal homogeneity for numerical stability, in uniform T1 weighted (T1w) images obtained with the magnetization prepared 2 rapid gradient echoes sequence (MP2RAGE) and to compare the clinical utility of these robust T1w images against the uniform T1w images. MATERIALS AND METHODS: 8 healthy subjects (29.0±4.1 years; 6 Male), who provided written consent, underwent two scan sessions within a 24 hour period on a 7T head-only scanner. The uniform and robust T1w image volumes were calculated inline on the scanner. Two experienced radiologists qualitatively rated the images for: general image quality; 7T specific artefacts; and, local structure definition. Voxel-based and volume-based morphometry packages were used to compare the segmentation quality between the uniform and robust images. Statistical differences were evaluated by using a positive sided Wilcoxon rank test. RESULTS: The robust image suppresses background noise inside and outside the skull. The inhomogeneity introduced was ranked as mild. The robust image was significantly ranked higher than the uniform image for both observers (observer 1/2, p-value = 0.0006/0.0004). In particular, an improved delineation of the pituitary gland, cerebellar lobes was observed in the robust versus uniform T1w image. The reproducibility of the segmentation results between repeat scans improved (p-value = 0.0004) from an average volumetric difference across structures of ≈6.6% to ≈2.4% for the uniform image and robust T1w image respectively. CONCLUSIONS: The robust T1w image enables MP2RAGE to produce, clinically familiar T1w images, in addition to T1 maps, which can be readily used in uniform morphometry packages.

Time-Lapse AFM Imaging of DNA Conformational Changes Induced by Daunorubicin.

Cancer is a major health issue that absorbs the attention of a large part of the biomedical research. Intercalating agents bind to DNA molecules and can inhibit their synthesis and transcription; thus, they are increasingly used as drugs to fight cancer. In this work, we show how atomic force microscopy in liquid can characterize, through time-lapse imaging, the dynamical influence of intercalating agents on the supercoiling of DNA, improving our understanding of the drug's effect.

Impact of navigator timing on free-breathing submillimeter 3D coronary magnetic resonance angiography.

The purpose of this study was to investigate the impact of navigator timing on image quality in navigator-gated and real-time motion-corrected, free-breathing, three-dimensional (3D) coronary MR angiography (MRA) with submillimeter spatial image resolution. Both phantom and in vivo investigations were performed. 3D coronary MRA with real-time navigator technology was applied using variable navigator time delays (time delay between the navigator and imaging sequences) and varying spatial resolutions. Quantitative objective and subjective image quality parameters were assessed. For high-resolution imaging, reduced image quality was found as a function of increasing navigator time delay. Lower spatial resolution coronary MRA showed only minor sensitivity to navigator timing. These findings were consistent among volunteers and phantom experiments. In conclusion, for submillimeter navigator-gated and real-time motion-corrected 3D coronary MRA, shortening the time delay between the navigator and the imaging portion of the sequence becomes increasingly important for improved spatial resolution.

Biased quantitative measurement of interval ordered homothetic preferences

We represent interval ordered homothetic preferences with a quantitative homothetic utility function and a multiplicative bias. When preferences are weakly ordered (i.e. when indifference is transitive), such a bias equals 1. When indifference is intransitive, the biasing factor is a positive function smaller than 1 and measures a threshold of indifference. We show that the bias is constant if and only if preferences are semiordered, and we identify conditions ensuring a linear utility function. We illustrate our approach with indifference sets on a two dimensional commodity space.

Spread spectrum magnetic resonance imaging.

We propose a novel compressed sensing technique to accelerate the magnetic resonance imaging (MRI) acquisition process. The method, coined spread spectrum MRI or simply s(2)MRI, consists of premodulating the signal of interest by a linear chirp before random k-space under-sampling, and then reconstructing the signal with nonlinear algorithms that promote sparsity. The effectiveness of the procedure is theoretically underpinned by the optimization of the coherence between the sparsity and sensing bases. The proposed technique is thoroughly studied by means of numerical simulations, as well as phantom and in vivo experiments on a 7T scanner. Our results suggest that s(2)MRI performs better than state-of-the-art variable density k-space under-sampling approaches.