Background-Molecular imaging of thrombus within fissures of vulnerable atherosclerotic plaques requires sensitive detection of a robust thrombus-specific contrast agent. In this study, we report the development and characterization of a novel ligand-targeted paramagnetic molecular imaging agent with high avidity for fibrin and the potential to sensitively detect active vulnerable plaques. Methods and Results-The nanoparticles were formulated with 2.5 to 50 mol% Gd-DTPA-BOA, which corresponds to Ͼ50 000 Gd 3ϩ atoms/particle. Paramagnetic nanoparticles were characterized in vitro and evaluated in vivo. In contradistinction to traditional blood-pool agents, T1 relaxation rate as a function of paramagnetic nanoparticle number was increased monotonically with Gd-DTPA concentration from 0.18 mL ⅐ s Ϫ1 · pmol Ϫ1 (10% Gd-DTPA nanoparticles) to 0.54 mL ⅐ s Ϫ1 · pmol Ϫ1 for the 40 mol% Gd-DTPA formulations. Fibrin clots targeted in vitro with paramagnetic nanoparticles presented a highly detectable, homogeneous T1-weighted contrast enhancement that improved with increasing gadolinium level (0, 2.5, and 20 mol% Gd). Higher-resolution scans and scanning electron microscopy revealed that the nanoparticles were present as a thin layer over the clot surface. In vivo contrast enhancement under open-circulation conditions was assessed in dogs. The contrast-to-noise ratio between the targeted clot (20 mol% Gd-DTPA nanoparticles) and blood was Ϸ118Ϯ21, and that between the targeted clot and the control clot was 131Ϯ37. Conclusions-These

Balanced steady-state free precession (SSFP) techniques provide excellent contrast between myocardium and blood at a high signal-to-noise ratio (SNR). Hence, SSFP imaging has become the method of choice for assessing cardiac function at 1.5T. The expected improvement in SNR at higher field strength prompted us to implement SSFP at 3.0T. In this work, an optimized sequence protocol for cardiac SSFP imaging at 3.0T is derived, taking into account several partly adverse effects at higher field, such as increased field inhomogeneities, longer T 1 , and power deposition limitations. SSFP contrast is established by optimizing the maximum amplitude of the radiofrequency (RF) field strength for shortest TR, as well as by localized linear or second-order shimming and local optimization of the resonance frequency. Given the increased SNR, sensitivity encoding (SENSE) can be employed to shorten breath-hold times. Shortaxis, long-axis, and four-chamber cine views obtained in healthy adult subjects are presented, and three different types of artifacts are discussed along with potential methods for reducing them.Magn The benefits of high-field (Ն3.0T) MR systems have been thoroughly explored for neuroimaging (1), functional imaging based on blood oxygenation level-dependent (BOLD) contrast (2), intracranial and cervical MRA (3), and spectroscopy of the head (4). Recently, work on cardiac imaging at 3.0T has demonstrated increased signal-to-noise ratio (SNR) with respect to imaging at 1.5T, in accordance with theory (5-7). Based on the initial data, it is expected that many cardiac imaging applications may benefit considerably from higher SNR. With the increasing availability of clinical 3.0T whole-body MR systems, cardiac imaging at 3.0T may become an important application in the near future.Standard cardiac imaging procedures for assesssing wall motion and ventricular function at 1.5T are based mainly on balanced steady-state free precession (SSFP) techniques (8) (also known as balanced fast field echo (bFFE), fast imaging employing steady-state acquisition (FIESTA), and fast imaging with steady precession (true FISP)). These sequences offer a high contrast-to-noise ratio (CNR) between myocardial muscle and oxygenated blood at a high SNR. The excellent CNR between myocardium and blood has been shown to greatly improve the reliability and robustness of imaging segmentation methods (9 -11).Concurrently with the success of SSFP imaging, parallel imaging techniques such as sensitivity encoding (SENSE) (12,13) have emerged as major tools for speeding up data acquisition. With respect to cardiac examinations, SENSE allows the use of shorter breath-holds; this in turn reduces the RF energy deposition in the subjects, which is a concern when imaging at higher field strength. With SENSE, the gain in speed is traded for a reduced SNR according to (12):where R denotes the reduction or acceleration factor, and g reflects the coil sensitivities, receiver noise correlation, and degree of reduction. The SNR loss with SENSE might be compens...

Myocardial tagging is a new noninvasive MRI method that allows the study of myocardial motion with high accuracy. However, with conventional tagging techniques tagging contrast is impaired at later heart phases due to longitudinal relaxation. An improved method, called Complementary SPAtial Modulation of Magnetization (CSPAMM), which separates the component of the magnetization with the tagging information from the relaxed component by subtraction of two measurements with first a positive and then a negative tagging grid, is presented. This technique improves the grid contrast and greatly facilitates the automatic evaluation of the myocardial motion. Thus the motion assessment of the entire heart cycle becomes possible. The improvements are documented by numerical simulations and by experiments on phantoms and on human volunteers.

Torsional behavior as observed in pressure- and volume-overloaded hearts is consistent with current theoretical findings. A delayed diastolic untwisting in the pressure-overloaded hearts of the patients may contribute to a tendency toward diastolic dysfunction.

No abstract

Dendritic cells phagocytose pathogens leading to maturation and cross-presentation on MHC class I. We found that the efficiency of cross-priming in mice after vaccination with biodegradable poly(D,L-lactide-co-glycolide) microspheres (MSs) was enhanced when ovalbumin was coencapsulated together with either a CpG oligonucleotide or polyI:C as compared to co-inoculation of ovalbumin-bearing MS with soluble or separately encapsulated adjuvants. A single immunization with MS containing coencaspsulated CpG and ovalbumin yielded 9% SIINFEKL/H-2K(b) tetramer positive CTLs, production of IFN-gamma, efficient cytolysis, and protection from vaccinia virus infection. Taken together, coencapsulation of adjuvant and antigen is an important paradigm for the generation of potent CTL responses.

Until now, a lack of inhibitors with high potency and selectivity in vivo has hampered investigation of the p38 mitogen-activated protein kinase (MAPK) signaling pathway. We describe the design of skepinone-L, which is, to our knowledge, the first ATP-competitive p38 MAPK inhibitor with excellent in vivo efficacy and selectivity. Therefore, skepinone-L is a valuable probe for chemical biology research, and it may foster the development of a unique class of kinase inhibitors.

Quantification of the lambda in vivo allows differentiation between normal and acutely or chronically infarcted myocardium, with high sensitivity and specificity.