A geometric calibration method that determines a complete description of source-detector geometry was adapted to a mobile C-arm for cone-beam computed tomography ͑CBCT͒. The non-iterative calibration algorithm calculates a unique solution for the positions of the sourceand detector rotation angles ͑ , , ͒ based on projections of a phantom consisting of two plane-parallel circles of ball bearings encased in a cylindrical acrylic tube. The prototype C-arm system was based on a Siemens PowerMobil modified to provide flat-panel CBCT for image-guided interventions. The magnitude of geometric nonidealities in the source-detector orbit was measured, and the short-term ͑ϳ4 h͒ and long-term ͑ϳ6 months͒ reproducibility of the calibration was evaluated. The C-arm exhibits large geometric nonidealities due to mechanical flex, with maximum departures from the average semicircular orbit of ⌬U o = 15.8 mm and ⌬V o = 9.8 mm ͑for the piercing point͒, ⌬X and ⌬Y =6-8 mm and ⌬Z =1 mm ͑for the source and detector͒, and ⌬ ϳ 2.9°, ⌬ ϳ 1.9°, and ⌬ ϳ 0.8°͑for the detector tilt/rotation͒. Despite such significant departures from a semicircular orbit, these system parameters were found to be reproducible, and therefore correctable by geometric calibration. Short-term reproducibility was Ͻ0.16 mm ͑subpixel͒ for the piercing point coordinates, Ͻ0.25 mm for the source-detector X and Y, Ͻ0.035 mm for the source-detector Z, and Ͻ0.02°for the detector angles. Long-term reproducibility was similarly high, demonstrated by image quality and spatial resolution measurements over a period of 6 months. For example, the full-width at half-maximum ͑FWHM͒ in axial images of a thin steel wire increased slightly as a function of the time ͑⌬͒ between calibration and image acquisition: FWHM= 0.62, 0.63, 0.66, 0.71, and 0.72 mm at ⌬ = 0 s, 1 h, 1 day, 1 month, and 6 months, respectively. For ongoing clinical trials in CBCT-guided surgery at our institution, geometric calibration is conducted monthly to provide sufficient three-dimensional ͑3D͒ image quality while managing time and workflow considerations of the calibration and quality assurance process. The sensitivity of 3D image quality to each of the system parameters was investigated, as was the tolerance to systematic and random errors in the geometric parameters, showing the most sensitive parameters to be the piercing point coordinates

Contrast injection protocol is known to affect the estimation of kinetic parameters in functional CT. A novel method is proposed to maximize the precision of parameter estimates by modulating the contrast injection scheme. The method models the intravenous contrast bolus to be dispersed by a "patient function" to give rise to the arterial input function, which, in turn, carries the contrast agent to tissue leading to contrast enhancement. The covariance matrix analysis was applied to calculate the uncertainty of parameter estimates as the coefficients of variation (CV) in the adiabatic tissue homogeneity (ATH), two-compartment, and the modified Kety model in which tumor pathophysiology is modeled. An optimization scheme was used to determine the optimal injection protocol which would minimize the CV of a particular kinetic parameter. For clinical utility, a recommended injection protocol was suggested from a statistical analysis with the optimal injection protocols obtained from the first group of 12 patients with cervix cancer. The efficacy of the recommended injection protocol was tested with a second group of 12 patients. In addition, the robustness of the recommended injection protocol to longitudinal study has been investigated in the presence of variations in arterial input function and tumor pathophysiology. Based on the data of the second group of patients, and using the ATH model, the recommended biphasic injection of two boluses improves the precision in the estimation of blood flow and mean transit time (MTT), by 36.9% and 38.4%, respectively, compared to the standard uniphasic injection protocol in the CV. However, measurement of the permeability surface area product and extravascular extracellular space volume favors a single fast bolus of the same contrast amount. The two-compartment model and the modified Kety model also benefited from the single fast bolus. The effect of variation in the arterial input function and tumor pathophysiology on the applicability of the recommended injection was also investigated. Based on computer simulation for a range of variations in the arterial input function and pathophysiology, the recommended biphasic injection was found to improve the precision in blood flow and MTT estimates by 31.4% and 36.5% on average, respectively, compared to the uniphasic injection.