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We present three new autoradiography methods to map positron emission rate of a bio-specimen slice with high resolution. One is based on LBNL scientific charge coupled device (CCD) and the other two are based on conventional CCDs. High conversion efficiency (100k e-h pairs / 0.5 MeV positron) and low dark current (1.75 × 10(-4) e-/pix/sec) can be achieved using the LBNL CCD. The theoretical calculations and preliminary experiments show that an 86 μm spatial resolution can be achieved when imaging a 100 μm thick tissue soaked with (18)F which produce higher energy positron. The main disadvantage of the LBNL CCD we tested is that a very low operating temperature is required to eliminate dark current. This dramatically increases the system cost. In addition, the integration time of the CCD needs to be short enough to avoid overlapping of the positron trajectories. Conventional CCDs have lower conversion efficiency (2k e-h pairs / 0.5 MeV positron) and higher dark current (200 e-/pix/sec), but are more cost-efficient and the requirement for the readout frequency is much lower. The conversion efficiency of the conventional CCD imager can be improved by 17 times by inserting a 100 μm layer of phosphor between the sample and the imager. However, the light emitted from the phosphor screen will be ~100 μm diameter, which severely degrades the spatial resolution. A high readout frequency is also required to avoid the overlapping. The CCD systems designed in this study will be used to map positron emission rate of bio-specimens such as cancerous tissues acquired in regular biopsy procedure. They can also be used to corroborate tracer kinetic modeling at a cellular level.