There's not enough pixels in the screens to do a perfect 2:2 pixel doubling to keep them perfect, sadly.
This. Due to how the PICA's upscaling works, not only will not it be pixel-perfect, but also the pixels will be jagged to hell.
Imagine an 1px straight line around the middle of the screen, and upscale it to the 3DS's screen resolution. The result will be jagged, and random pixels will have shifted upwards, and it looks absolutely horrible.