Table 1 Grey-level size-zone matrix features

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 Z_ijj² /nzones

HGZE

High Grey-level Zone Emphasis

indicative of the presence of areas with high drug concentrations, regardless of their size

∑_ij Z_iji² /nzones

LZHGE

Large-zone High Grey-level Emphasis

focuses on the presence of wide areas with high drug concentrations

∑_ij Z_ijj² 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 Z_ij)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 Z_ij)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 Z_ijj /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 Z_ij /∑_{i,j ≥ ν} Z_ij /npix