A method of using a mobile x-ray radiography apparatus (1000; 1200; 1300) comprising one or more handle grips for manually guiding the apparatus (1000; 1200; 1300), a battery pack for providing power to the apparatus (1000; 1200; 1300), one or more wheels for rolling the apparatus (1000; 1200; 1300), a support column (135; 1030), optionally a section that extends outward from the support column (135; 1030) and that is configured to ride vertically up and down the support column (135; 1030), one or more x-ray sources (140; 340; 1040; 1240; 1520) attached to the support column (135; 1030) or to the section, and one or more processors, the method comprising performing the steps of: manually guiding the mobile radiography apparatus (1000; 1200; 1300) to a location proximate an object by using the one or more handle grips and the one or more wheels on the mobile radiography apparatus (1000; 1200; 1300); manually positioning a portable x-ray detector (1050; 1540) adjacent the object; the one or more processors controlling movement of the one or more x-ray sources (140; 340; 1040; 1240; 1520) through a plurality of x-ray source imaging positions by extending the support column (135; 1030) and/or the section attached to the support column (135; 1030) using motor control, and activating the one or more x-ray sources (140; 340; 1040; 1240; 1520) at each of the x-ray source imaging positions using power from the battery pack contained in the mobile radiography apparatus (1000; 1200; 1300) to direct x-ray beams through the object toward the x-ray detector (1050; 1540); obtaining a plurality of x-ray tomosynthesis projection images of the object in the x-ray detector (1050; 1540) using the one or more x-ray sources (140; 340; 1040; 1240; 1520) and transmitting the x-ray projection images from the x-ray detector (1050; 1540) to the one or more processors; generating a three-dimensional reconstruction of the object using the obtained plurality of x-ray projection images; generating the three-dimensional reconstruction of the object using a current imaging geometry estimate for the plurality of tomographic projection images; determining a tomographic reconstruction performance metric for a current three-dimensional reconstruction of the object; comparing the tomographic reconstruction performance metric for the current three-dimensional reconstruction of the object to a stopping criterion; and setting the current imaging geometry estimate to an adjusted imaging geometry and repeating the steps of generating through setting when the tomographic reconstruction performance metric has not satisfied the stopping criterion, otherwise storing the current three-dimensional reconstruction of the object and the current imaging geometry estimate in a computer-accessible memory; and where a starting imaging geometry of the plurality of x-ray source imaging positions and the x-ray detector (1050; 1540) is not known for the plurality of x-ray tomosynthesis projection images. manually guiding the mobile radiography apparatus (1000; 1200; 1300) to a location proximate an object by using the one or more handle grips and the one or more wheels on the mobile radiography apparatus (1000; 1200; 1300); manually positioning a portable x-ray detector (1050; 1540) adjacent the object; the one or more processors controlling movement of the one or more x-ray sources (140; 340; 1040; 1240; 1520) through a plurality of x-ray source imaging positions by extending the support column (135; 1030) and/or the section attached to the support column (135; 1030) using motor control, and activating the one or more x-ray sources (140; 340; 1040; 1240; 1520) at each of the x-ray source imaging positions using power from the battery pack contained in the mobile radiography apparatus (1000; 1200; 1300) to direct x-ray beams through the object toward the x-ray detector (1050; 1540); obtaining a plurality of x-ray tomosynthesis projection images of the object in the x-ray detector (1050; 1540) using the one or more x-ray sources (140; 340; 1040; 1240; 1520) and transmitting the x-ray projection images from the x-ray detector (1050; 1540) to the one or more processors; generating a three-dimensional reconstruction of the object using the obtained plurality of x-ray projection images; generating the three-dimensional reconstruction of the object using a current imaging geometry estimate for the plurality of tomographic projection images; determining a tomographic reconstruction performance metric for a current three-dimensional reconstruction of the object; comparing the tomographic reconstruction performance metric for the current three-dimensional reconstruction of the object to a stopping criterion; and setting the current imaging geometry estimate to an adjusted imaging geometry and repeating the steps of generating through setting when the tomographic reconstruction performance metric has not satisfied the stopping criterion, otherwise storing the current three-dimensional reconstruction of the object and the current imaging geometry estimate in a computer-accessible memory; and where a starting imaging geometry of the plurality of x-ray source imaging positions and the x-ray detector (1050; 1540) is not known for the plurality of x-ray tomosynthesis projection images.