CellDF: Quality-controlled cell matching for whole-slide HE-IHC label transfer

Serial-section immunohistochemistry (IHC) is the largest available source of paired hematoxylin and eosin (HE) and IHC whole slide images, yet it remains underexploited for cell-level supervision: adjacent sections sample non-identical cells, and residual registration error prevents direct assignment of IHC labels to individual HE cells. We present CellDF (Cell Displacement Field), which turns registered serial-section data into pairs of HE cells and their IHC labels by solving cell matching at whole-slide scale and assessing its reliability without ground-truth correspondences. CellDF estimates a locally adaptive residual displacement field through iterated kernel regression over each HE cell’s K nearest IHC candidates; a sparse-kernel variant keeps it tractable at the cell counts of a whole slide, where pairwise matchers are not. The within-tile distribution of the estimated displacements yields two ground-truth-free statistics, the directional scatter σ _θ and the between-tile angular deviation | Δθ |, that localize matching quality more finely than landmark-based target registration error and drive a two-stage outlier filter that withholds labels where matching is unreliable. On 54 same-section HyReCo pairs, σ _θ correlates only moderately with landmark error and flags localized restaining damage that global error misses; on 30 four-marker Acrobat serial-section cases, the same statistic flags which IHC marker, if any, lies physically close enough to HE to support cell-level transfer. As a proof of concept, IHC labels transferred through CellDF trained a cell classifier on HE embeddings that generalized to held-out cells within the sample (F1 0.85, AUROC 0.88), establishing serial-section IHC as a usable cell-level labeling resource.