Volumetric bone marrow cellularity (VBMC) assessment from routinely processed trephines using three-dimensional x-ray histology and gaussian peak modelling.

Stephanie K Robinson; Elizabeth Morris; Sofia Michopoulou; Richard P Boardman; Kim Orchard; Philipp Schneider; Alex Dickinson; Orestis L Katsamenis

doi:10.1088/1361-6560/ae9c84

PubMed · 42624159

Volumetric bone marrow cellularity (VBMC) assessment from routinely processed trephines using three-dimensional x-ray histology and gaussian peak modelling.

Stephanie K Robinson·Elizabeth Morris·Sofia Michopoulou·Richard P Boardman·Kim Orchard·Philipp Schneider·Alex Dickinson·Orestis L Katsamenis

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Abstract

Objective.Bone marrow cellularity is routinely estimated from a small number of two-dimensional histology sections, making assessment sensitive to section representativeness, processing artefacts and observer interpretation. Three-dimensional (3D) x-ray histology (XRH), using x-ray computed microtomography (µCT), enables non-destructive whole-block imaging of trephine biopsies. This study evaluated whether XRH combined with Gaussian peak modelling could provide a pragmatic whole-block volumetric bone marrow cellularity (VBMC) estimate from formalin-fixed paraffin-embedded (FFPE) trephine biopsy blocks.Approach.Six routinely processed FFPE bone marrow trephine blocks were imaged using µCT-based XRH at ∼15 µm spatial resolution. VBMC was defined as the red-marrow (RM) fraction of the marrow soft-tissue compartment, RM/(RM + intra-biopsy wax), with wax serving as the volumetric proxy for adipocyte/yellow marrow space. Whole-volume greyscale histograms were modelled using a three-peak Gaussian approach representing intra-biopsy wax, RM and demineralised trabecular matrix. Peak-height and area-under-the-curve metrics were compared with whole-volume 3D segmentation and clinical two-dimensional (2D) cellularity estimates.Main Results.Gaussian peak modelling successfully approximated the segmented tissue-phase distributions. The peak-height-derived VBMC metric showed the closest agreement with whole-volume 3D segmentation, with an average absolute percentage difference of 9.3%, compared with 18.6% for clinical expert 2D cellularity estimates. The area-under-the-curve metric followed similar trends but consistently overestimated VBMC. Clinical 2D cellularity broadly followed whole-biopsy trends but showed one discordant case not explained by slice-position sampling alone. XRH also enabled unrestricted virtual reslicing and visualisation of sectioning-associated artefacts prior to further microtomy.Significance.Pre-sectioning XRH combined with Gaussian peak modelling provides a rapid, segmentation-free route to volumetric cellularity estimation from intact clinical FFPE trephine blocks. The approach supports objective whole-biopsy assessment while remaining compatible with routine histopathology workflows, reflecting the expected limitations of section-based visual estimation despite its role as the current clinical standard. In the near term, it could provide a non-disruptive adjunct to conventional 2D cellularity reporting, pending larger validation studies.

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Imaging, Three-Dimensional Normal Distribution Humans Bone Marrow Cells X-Ray Microtomography Bone Marrow 3D x-ray histology (XRH)bone marrow cellularity computed tomography digital pathology gaussian peak modelling micro-CT Journal Article

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Stephanie K Robinson, Elizabeth Morris, Sofia Michopoulou, Richard P Boardman, Kim Orchard, Philipp Schneider, Alex Dickinson, Orestis L Katsamenis. 2026-09-01. Volumetric bone marrow cellularity (VBMC) assessment from routinely processed trephines using three-dimensional x-ray histology and gaussian peak modelling.. https://doi.org/10.1088/1361-6560%2Fae9c84

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