Various approaches are discussed for using four-side buttable CMOS tiles to fabricate detector panels, including large-area detector panels. Fabrication may utilize pads and interconnect structures formed on the top or bottom of the CMOS tiles. Electrical connection and readout may utilize readout and digitization circuitry provided on the CMOS tiles themselves such that readout of groups or sub-arrays of pixels occurs at the tile level, while tiles are then readout at the detector level such that readout operations are tiered or multi-level.