Table 1.

Grey-level size-zone matrix features

Abbreviation	Name	Description	Mathematical formula
ZP	Zone percentage	lower values indicate that the image is made of a few large zones with the same grey-level. Higher values indicate greater fragmentation of the image into small zones	nzones/npix
LZE	Large zone emphasis	associated with the presence of wide areas with similar drug concentrations, regardless of whether they are low or high	∑ij Zijj2 /nzones
HGZE	High Grey-level Zone Emphasis	indicative of the presence of areas with high drug concentrations, regardless of their size	∑ij Ziji2 /nzones
LZHGE	Large-zone High Grey-level Emphasis	focuses on the presence of wide areas with high drug concentrations	∑ij Zijj2 i2 /nzone
IV	Intensity variability	highest when there are few large zones with low drug concentrations. It decreases when the concentration increases and smaller zones are formed with higher drug concentrations	∑i (∑j Zij)2/i4/nzones
GLNn	Grey-Level Non-uniformity normalised	highest when zones concentrate to a single grey level, lower when all grey levels are equally represented (poorly sensitive to redistribution among grey levels)	(∑i (∑j Zij)2 /nzones)/nzones
ZSμ	Zone Size mean	average size of the zones, independently of the grey level. Strongly affected by the presence of a large number of small zones	∑ij Zijj /nzones
DHI	Drug-homogeneity index	a recently proposed feature measuring the average area of the larger zones (over a given arbitrary threshold ν) as a fraction of the ROI area	∑i,j ≥ ν j Zij /∑i,j ≥ ν Zij /npix

i: grey levels; j: zone sizes; nzones: total number of zones; npix: total number of pixels in the ROI