Identification of patients who will benefit from a specific therapeutic procedure requires the accurate assessment of the severity of stenoses, their geometry and spatial orientation. Most therapeutic decisions are currently based on information obtained through digital subtraction angiography. Standard angiographic images are not providing angiographers with sufficient information needed to make therapeutic decisions. The long-term goal of this four year project is to continually develop a three-dimensional (3-D) tomographic (called volume tomographic) digital angiography imaging technique to provide useful 3-D vascular images needed for diagnostic and therapeutic decisions. Volume tomographic digital angiography (VTDA) combines volume tomographic imaging principles with those of digital angiography. VTDA requires only a single intravenous contrast injection and volume scan to provide a true description of vascular anatomy and stenoses in head and neck. This VTDA technique will be superior to conventional angiography and have a strong clinical impact because it will provide a direct, unambiguous and accurate 3D measurement of stenoses and other irregularities and malformations, including caliber, geometry and spatial orientation, while reducing the invasiveness of the procedure, the amount of contrast media required, procedure time and total X-ray exposure. VTDA continues to be developed and validated through computer simulation, phantom, and animal studies performed on a rotational volume tomographic imager that uses a selenium thin film transistor (STFT) array or an image intensifier (II) coupled to a charge-coupled device (CCD) as a detector. Specifically, the aim of the proposed research is: 1) to perform studies on optimization of VTDA through computer simulation; 2) to optimize cone beam vascular reconstruction algorithms; 3) use the upgraded II-based VTDA system to develop and evaluate new scanning modes and develop the STFT-based prototype imaging system for ultimate intravenous contrast injection; 4) to perform phantom studies to validate the VTDA technique and optimize the system performance; and 5) to use the prototype imager for animal experiments as a prelude to human studies; and 6) to perform the clinical studies in neck and brain based on the optimized injection and volume scanning protocols developed in animal studies.