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Background— Platelets are the key to thrombus formation and play a role in the development of atherosclerosis. Noninvasive imaging of activated platelets would be of great clinical interest. Here, we evaluate the ability of a magnetic resonance imaging (MRI) contrast agent consisting of microparticles of iron oxide (MPIOs) and a single-chain antibody targeting ligand-induced binding sites (LIBS) on activated glycoprotein IIb/IIIa to image carotid artery thrombi and atherosclerotic plaques. Methods and Results— Anti-LIBS antibody or control antibody was conjugated to 1-μm MPIOs (LIBS MPIO/control MPIO). Nonocclusive mural thrombi were induced in mice with 6% ferric chloride. MRI (at 9.4 T) was performed once before and repeatedly in 12-minute-long sequences after LIBS MPIO/control MPIO injection. After 36 minutes, a significant signal void, corresponding to MPIO accumulation, was observed with LIBS MPIOs but not control MPIOs ( P P Conclusions— LIBS MPIOs allow in vivo MRI of activated platelets with excellent contrast properties and monitoring of thrombolytic therapy. Furthermore, activated platelets were detected on the surface of symptomatic human carotid plaques by ex vivo MRI. This approach represents a novel noninvasive technique allowing the detection and quantification of platelet-containing thrombi.

Background: Platelets are the key to thrombus formation and play a major role in plaque rupture. Here, we evaluate theabilityof amagnetic resonance imaging (MRI) contrast agent consisting of microparticles of iron oxide (MPIO) and a single-chain antibody targeting ligandinduced binding sites (LIBS) on activated GPIIb/IIIa to image carotid artery thrombi. Methods and results: Anti-LIBS or control antibody were conjugated to 1 m-sized MPIOs (LIBS–MPIO/control–MPIO). Non-occlusive mural thrombi were induced in BL/6 mice using 6% ferricchloride. MRI (9.4 T) of the carotid artery was performed once before and repeatedly in 12min long sequences after LIBS–MPIO/control–MPIO injection. After 36min, a significant signal void, which is the typical effect of iron oxide-based contrast agents and which notably extends beyond the particle size, was observed with LIBS–MPIO, but not control–MPIO (P< 0.01) and corresponded to LIBS–MPIO binding as confirmed by histology. After thrombolysis, in LIBS–MPIO injectedmice the signal void subsided, indicating successful thrombolysis. On histology, MPIO-content of thrombus, as well as thrombus size, correlated significantly with LIBS–MPIO-induced signal void (both P< 0.01). Conclusions: We describe a novel approach for molecular imaging allowing in vivo targeting of magnetic resonance contrast agents to activated platelets. Thereby, thrombi canbedetectedwithexcellent resolutionandcontrast properties, which are suitable for coronary artery imaging in humans. Furthermore, success or failure of thrombolytic therapy can be monitored. This novel non-invasive technique provides rapid detection and quantification of thrombi, such as found in myocardial infarction, pulmonary embolism and on the surface of ruptured or rupture-prone atherosclerotic plaques.

Conceptual and preliminary engineering design for the National RF Test Facility at Oak Ridge National Laboratory (ORNL) has been completed. The facility will comprise a single mirror configuration embodying two superconducting development coils from the ELMO Bumpy Torus Proof-of-Principle (EBT-P) program on either side of a cavity designed for full-scale antenna testing. The coils are capable of generating a 1.2-T field at the axial midpoint between the coils separated by 1.0 m. The vacuum vessel will be a stainless steel, water-cooled structure having an 85-cm-radius central cavity. The facility will have the use of a number of continuous wave (cw), radio-frequency (rf) sources at levels including 600 kW at 80 MHz and 100 kW at 28 GHz. Several plasma sources will provide a wide range of plasma environments, including densities as high as approx. 5 x 10/sup 13/ cm/sup -3/ and temperatures on the order of approx. 10 eV. Furthermore, a wide range of diagnostics will be available to the experimenter for accurate appraisal of rf testing.

Multimegawatt neutral beams of hydrogen or deuterium atoms are needed for fusion machine applications such as MFTB-B, TFTR-U, DIII-U, and FED (INTOR or ETR). For these applications, a duoPIGatron ion source is being developed to produce high-brightness deuterium beams at a beam energy of approx. 120 keV for pulse lengths up to 30 s. A long-pulse plasma generator with active water cooling has been operated at an arc level of 1200 A with 30-s pulse durations. The plasma density and uniformity are sufficient for supplying a 60-A beam of hydrogen ions to a 13- by 43-cm accelerator. A 10- by 25-cm tetrode accelerator has been operated to form 120-keV hydrogen ion beams. Using the two-dimensional (2-D) ion extraction code developed at Oak Ridge National Laboratory (ORNL), a 13- by 43-cm tetrode accelerator has been designed and is being fabricated. The aperture shapes of accelerator grids are optimized for 120-keV beam energy.

This paper describes the development of a long-pulse positive ion source that has been designed to provide high brightness deuterium beams (divergence ≈ 0.25° rms, current density ≈ 0.15 A cm-2) of 40-45 A, at a beam energy of 80 keV, for pulse lengths up to 30 s. The design and construction of the ion source components are described with particular emphasis placed on the long-pulse cathode assembly and ion accelerator.