Virtual Region or Compare Stored Images

Consider a scenario.

1. Two images are stored in file system.
2. Check if second image is contained in first image.

One of the possible ways I could do was,
1. Load the first image onto browser or Launch it using Preview(Mac).
2. Create a region.
r = Region(10, 10, 350, 400)
3. use r.exists(image2)

It would be nice if loading / launching the first image could be avoided.

Is it possible ?

I studied http://sikuli.org/docx/region.html, and noted that Region uses SCREEN co-ordinates. Is there a way to create a Region for an image stored in file system.