Methods, methods of making, devices, and systems for image sensors that include isolation regions are disclosed. A semiconductor imager includes a pixel array and peripheral circuitry arranged on at least one side of the pixel array. Array devices are formed as part of the pixel array and periphery devices are formed in the periphery. Array isolation regions are disposed around at least a portion of at least some of the array devices and periphery isolation regions are disposed around at least a portion of at least some of the periphery devices. Within the semiconductor imager, the periphery isolation regions are configured differently from the array isolation regions. The semiconductor image sensor may be included in as part of an imaging system that includes a processor.