Robust volume-targeted balanced steady-state free-precession coronary magnetic resonance angiography in a breathhold at 3.0 Tesla: a reproducibility study.

BACKGROUND: Transient balanced steady-state free-precession (bSSFP) has shown substantial promise for noninvasive assessment of coronary arteries but its utilization at 3.0 T and above has been hampered by susceptibility to field inhomogeneities that degrade image quality. The purpose of this work was to refine, implement, and test a robust, practical single-breathhold bSSFP coronary MRA sequence at 3.0 T and to test the reproducibility of the technique. METHODS: A 3D, volume-targeted, high-resolution bSSFP sequence was implemented. Localized image-based shimming was performed to minimize inhomogeneities of both the static magnetic field and the radio frequency excitation field. Fifteen healthy volunteers and three patients with coronary artery disease underwent examination with the bSSFP sequence (scan time = 20.5 ± 2.0 seconds), and acquisitions were repeated in nine subjects. The images were quantitatively analyzed using a semi-automated software tool, and the repeatability and reproducibility of measurements were determined using regression analysis and intra-class correlation coefficient (ICC), in a blinded manner. RESULTS: The 3D bSSFP sequence provided uniform, high-quality depiction of coronary arteries (n = 20). The average visible vessel length of 100.5 ± 6.3 mm and sharpness of 55 ± 2% compared favorably with earlier reported navigator-gated bSSFP and gradient echo sequences at 3.0 T. Length measurements demonstrated a highly statistically significant degree of inter-observer (r = 0.994, ICC = 0.993), intra-observer (r = 0.894, ICC = 0.896), and inter-scan concordance (r = 0.980, ICC = 0.974). Furthermore, ICC values demonstrated excellent intra-observer, inter-observer, and inter-scan agreement for vessel diameter measurements (ICC = 0.987, 0.976, and 0.961, respectively), and vessel sharpness values (ICC = 0.989, 0.938, and 0.904, respectively). CONCLUSIONS: The 3D bSSFP acquisition, using a state-of-the-art MR scanner equipped with recently available technologies such as multi-transmit, 32-channel cardiac coil, and localized B0 and B1+ shimming, allows accelerated and reproducible multi-segment assessment of the major coronary arteries at 3.0 T in a single breathhold. This rapid sequence may be especially useful for functional imaging of the coronaries where the acquisition time is limited by the stress duration and in cases where low navigator-gating efficiency prohibits acquisition of a free breathing scan in a reasonable time period

Spatially selective implementation of the adiabatic T2 prep sequence for magnetic resonance angiography of the coronary arteries.

In coronary magnetic resonance angiography, a magnetization-preparation scheme for T2 -weighting (T2 Prep) is widely used to enhance contrast between the coronary blood-pool and the myocardium. This prepulse is commonly applied without spatial selection to minimize flow sensitivity, but the nonselective implementation results in a reduced magnetization of the in-flowing blood and a related penalty in signal-to-noise ratio. It is hypothesized that a spatially selective T2 Prep would leave the magnetization of blood outside the T2 Prep volume unaffected and thereby lower the signal-to-noise ratio penalty. To test this hypothesis, a spatially selective T2 Prep was implemented where the user could freely adjust angulation and position of the T2 Prep slab to avoid covering the ventricular blood-pool and saturating the in-flowing spins. A time gap of 150 ms was further added between the T2 Prep and other prepulses to allow for in-flow of a larger volume of unsaturated spins. Consistent with numerical simulation, the spatially selective T2 Prep increased in vivo human coronary artery signal-to-noise ratio (42.3 ± 2.9 vs. 31.4 ± 2.2, n = 22, P < 0.0001) and contrast-to-noise-ratio (18.6 ± 1.5 vs. 13.9 ± 1.2, P = 0.009) as compared to those of the nonselective T2 Prep. Additionally, a segmental analysis demonstrated that the spatially selective T2 Prep was most beneficial in proximal and mid segments where the in-flowing blood volume was largest compared to the distal segments. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc

Regional coronary endothelial function is closely related to local early coronary atherosclerosis in patients with mild coronary artery disease: pilot study.

BACKGROUND: Coronary endothelial function is abnormal in patients with established coronary artery disease and was recently shown by MRI to relate to the severity of luminal stenosis. Recent advances in MRI now allow the noninvasive assessment of both anatomic and functional (endothelial function) changes that previously required invasive studies. We tested the hypothesis that abnormal coronary endothelial function is related to measures of early atherosclerosis such as increased coronary wall thickness. METHODS AND RESULTS: Seventeen arteries in 14 healthy adults and 17 arteries in 14 patients with nonobstructive coronary artery disease were studied. To measure endothelial function, coronary MRI was performed before and during isometric handgrip exercise, an endothelial-dependent stressor, and changes in coronary cross-sectional area and flow were measured. Black blood imaging was performed to quantify coronary wall thickness and indices of arterial remodeling. The mean stress-induced change in cross-sectional area was significantly higher in healthy adults (13.5%±12.8%, mean±SD, n=17) than in those with mildly diseased arteries (-2.2%±6.8%, P<0.0001, n=17). Mean coronary wall thickness was lower in healthy subjects (0.9±0.2 mm) than in patients with coronary artery disease (1.4±0.3 mm, P<0.0001). In contrast to healthy subjects, stress-induced changes in cross-sectional area, a measure of coronary endothelial function, correlated inversely with coronary wall thickness in patients with coronary artery disease (r=-0.73, P=0.0008). CONCLUSIONS: There is an inverse relationship between coronary endothelial function and local coronary wall thickness in patients with coronary artery disease but not in healthy adults. These findings demonstrate that local endothelial-dependent functional changes are related to the extent of early anatomic atherosclerosis in mildly diseased arteries. This combined MRI approach enables the anatomic and functional investigation of early coronary disease

Sound Control-Flow Graph Extraction for Java Programs with Exceptions

We present an algorithm to extract control-flow graphs from Java bytecode, considering exceptional flows. We then establish its correctness: the behavior of the extracted graphs is shown to be a sound over-approximation of the behavior of the original programs. Thus, any temporal safety property that holds for the extracted control-flow graph also holds for the original program. This makes the extracted graphs suitable for performing various static analyses, in particular model checking. The extraction proceeds in two phases. First, we translate Java bytecode into BIR, a stack-less intermediate representation. The BIR transformation is developed as a module of Sawja, a novel static analysis framework for Java bytecode. Besides Sawja’s efficiency, the resulting intermediate representation is more compact than the original bytecode and provides an explicit representation of exceptions. These features make BIR a natural starting point for sound control-flow graph extraction. Next, we formally define the transformation from BIR to control-flow graphs, which (among other features) considers the propagation of uncaught exceptions within method calls. We prove the correctness of the two-phase extraction by suitably combining the properties of the two transformations with those of an idealized control-flow graph extraction algorithm, whose correctness has been proved directly. The control-flow graph extraction algorithm is implemented in the \textsc{ConFlEx} tool. A number of test-cases show the efficiency and the utility of the implementation

Vessel centerline tracking and boundary sgementation in coronary MRA with minimal manual interaction.

Magnetic resonance angiography (MRA) provides a noninvasive means to detect the presence, location and severity of atherosclerosis throughout the vascular system. In such studies, and especially those in the coronary arteries, the vessel luminal area is typically measured at multiple cross-sectional locations along the course of the artery. The advent of fast volumetric imaging techniques covering proximal to mid segments of coronary arteries necessitates automatic analysis tools requiring minimal manual interactions to robustly measure cross-sectional area along the three-dimensional track of the arteries in under-sampled and non-isotropic datasets. In this work, we present a modular approach based on level set methods to track the vessel centerline, segment the vessel boundaries, and measure transversal area using two user-selected endpoints in each coronary of interest. Arterial area and vessel length are measured using our method and compared to the standard Soap-Bubble reformatting and analysis tool in in-vivo non-contrast enhanced coronary MRA images

In vitro antileishmanial activity and apoptosis induction of Pleurotus ostreatus alcoholic extract on Leishmania major

Background and objectives: Leishmaniasis is caused by the genus Leishmania. Medications such as antimony compounds for the treatment of the disease are associated with limitations along with several side effects and disease recurrence; thus, evaluation of natural compounds with history of antimicrobial properties such as   Pleurotus ostreatus, is of a great importance. The purpose of this study was to evaluate the apoptotic and leishmanicidal effects of Pleurotus ostreatus alcoholic extract on Leishmania major promastigote in vitro. Methods: Different concentrations of Pleurotus ostreatus extract (50, 100, 150, 200 and 250 μg/mL) were tested at 6, 24, 48 and 72 h on Leishmania major (MRHO/IR/75/ER) promastigotes. The leishmanicidal effects were determined using MTT [3-(4,5-dimethyl thiazolyl- 2)-2,5-diphenyle tetrazolium bromide] assay. Also, apoptosis induction was measured by flow cytometry and DNA fragmentation analysis. Results:The MTT results showed that leishmanicidal effect of Pleurotus ostreatus extract was dependent to extract concentration in a way that the lowest number of live promastigotes was obtained after treatment with 200 μg/mL of extract preparation at 72 h. The IC50 of Pleurotus ostreatus extract was 160±2 μg/mL. Flow cytometric analysis showed that the extract could induce apoptosis in promastigotes at its IC50. Also, the result of gel electrophoresis showed that DNA fragmentation of treated promastigotes at the same concentration. Conclusion: The results indicated that Pleurotus ostreatus alcoholic extract have a strong toxic effect on cultivated Leishmania parasites. Based on these results in vivo studies using rodent models and human cutaneous leishmaniasis CL is recommended