? The aim of this proposal is to develop a dynamic micro-computed tomography (micro-CT) system with enhanced spatial and temporal resolution and more versatile imaging capabilities compared to the current commercial micro-CT scanners, and to explore its applications for biomedical research. The goal is to provide a scanner that will maximize image resolution for in vivo scanning of mice and with the target organ systems being the cardiopulmonary system. The proposed system will utilize a micro-focus field-emission x-ray source recently demonstrated in our laboratory. Compared to the conventional micro-focus x-ray sources with thermionic cathodes, the new carbon nanotube (CNT) based field emission x-ray source offers high resolution at significantly reduced size, fast pulsation capability currently not possible, and the potential for higher flux. The proposed CT scanner with the gated field-emission x-ray source, digital 2D x-ray detector and motorized object stage can synchronize x-ray exposure, data collection, objection rotation and the physiological signal of the object. The system will enable triggered and gated imaging at the rate of 1-10 millisecond (msec) per image, and will have a resolution of 30 gm or less. These capabilities, which have not been demonstrated in the current gated micro-CT systems, will provide new imaging modalities for biomedical research such as dynamic cardiac and pulmonary imaging of small animals. When fully implemented, dynamic CT images of a full cycle of cardiac motion can be obtained in 10 minutes. The new design will also significantly reduce the cost and physical size of the micro-CT scanner and thus making the technology more readily available for the research community. ? ? A substantial amount of preliminary results have been obtained and they have confirmed the validity of our hypothesis. We have also established extensive infrastructure in nanotechnology, which will be leveraged for this proposed research. We expect this proposed research will have a high degree of probability of success. ? ? In the R21 Phase (Year 1) we will design, construct and evaluate a triode-type field emission x-ray source using CNTs as the electron source. The targeted characteristics of the x-ray source are: 100-500?A tube current at 30?m resolution, 40-100KVp, programmable pulse width and repetition rate (less than 0.1 misec width at up to 10KHz) and less than 1% fluctuation in flux. We will further design and construct a field emission x-ray source with electronicallyselective variable focal spot sizes. The imaging capability and performance characteristics of the x-ray tubes will be evaluated and compared with the commercial micro-focus x-ray sources. ? ? In the R33 Phase (Year 2-4) we will assemble a dynamic micro-CT scanner using the field emission x-ray source, a commercial high-resolution fast-response digital two-dimensional x-ray detector, and cone-beam reconstruction algorithm. User interface, instrumentation control and imaging softwares will be developed. By electronically synchronizing x-ray exposure, data collection, object motion, and physiological signals, the system will enable dynamic CT imaging with high spatial and temporal resolution. After calibration we will demonstrate 1) high resolution imaging of ?ENaC transgenic mice airway to asses the relationship of survive rate to the quantity of mucus present; 2) dynamic imaging of cardiac and pulmonary motion. ? ? We have assembled a team of leading scientists and engineers in the fields of materials science, medical physics, radiology, and physiology from UNC (Zhou, Lu, Grubb, Lin and Boucher), NCSU (Lalush) and U of Iowa (Hoffman, McLennan). The research will be carried out primarily at the North Carolina Center of Nanoscale Materials at UNC where this PI is the founding director. Zhou and Lu have extensive experiences in the CNT field emission technology and are among the first to demonstrate a cold-cathode x-ray tube using the CNTs. They will be primarily responsible for the instrumentation development. Lalush will be responsible for the image reconstruction effort. Hoffman and McLennan are leading experts in the area of dynamic, volumetric cardiopulmonary CT imaging and image analysis. They will advise the CT design, compare its performance with the commercial system and use the system for dynamic imaging in a test application: smoking mouse model of emphysema. Grubb, Lin, and Boucher will utilize the CT scanner at UNC to evaluate airway pathology. ? ?
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