'How can I go about averaging different sized images?

I have a collection of images from tissue sections which contain a specific area of interest. Given this is biology, each image is slightly different (position of the area of interest, noise levels, signal intensity, etc): I need to quantify the signal intensity distribution in the area of interest from control and experimental samples, compare them and perform statistical testing to see if it is any different between both groups. After extracting the region of interest from each image into a new image, the first problem is to compare different sized images in order to calculate the mean for each group...I am guessing I will have to resize to the smallest/biggest image but that will affect the spatial distribution of the signal...how would you go about it?

I attach 3 example images to illustrate my problem, following @Esraa Abdelmaksoud suggestion.

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Solution 1:[1]

I would suggest dividing intensity by the total area. In addition, if you are particularly interested in a region of interest, depending on your biological question, I would also suggest getting rid of the background- You seem to have a different area of background in each image.

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Solution Source
Solution 1 Ajit Johnson Nirmal