MarrowQuant 2.0: A Digital Pathology Workflow Assisting Bone Marrow Evaluation in Experimental and Clinical Hematology

Rita Sarkis; Olivier Burri; Claire Royer-Chardon; Frédérica Schyrr; Sophie Blum; Mariangela Costanza; Stephane Cherix; Nathalie Piazzon; Carmen Barcena; Bettina Bisig; Valentina Nardi; Rossella Sarro; Giovanna Ambrosini; Martin Weigert; Olivier Spertini; Sabine Blum; Bart Deplancke; Arne Seitz; Laurence de Leval; Olaia Naveiras

doi:10.1016/j.modpat.2022.100088

MarrowQuant 2.0: A Digital Pathology Workflow Assisting Bone Marrow Evaluation in Experimental and Clinical Hematology

Mod Pathol. 2023 Apr;36(4):100088. doi: 10.1016/j.modpat.2022.100088. Epub 2023 Jan 10.

Authors

Rita Sarkis¹, Olivier Burri², Claire Royer-Chardon³, Frédérica Schyrr⁴, Sophie Blum⁴, Mariangela Costanza⁵, Stephane Cherix⁶, Nathalie Piazzon³, Carmen Barcena⁷, Bettina Bisig³, Valentina Nardi⁸, Rossella Sarro⁹, Giovanna Ambrosini¹⁰, Martin Weigert¹¹, Olivier Spertini⁵, Sabine Blum⁵, Bart Deplancke¹², Arne Seitz², Laurence de Leval³, Olaia Naveiras¹³

Affiliations

¹ Laboratory of Regenerative Hematopoiesis, Institute of Bioengineering & ISREC, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland; Department of Biomedical Sciences, University of Lausanne (UNIL), Lausanne, Switzerland; Laboratory of Systems Biology and Genetics, Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
² BioImaging and Optics Core Facility, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
³ Institute of Pathology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and Lausanne University, Lausanne, Switzerland.
⁴ Laboratory of Regenerative Hematopoiesis, Institute of Bioengineering & ISREC, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
⁵ Hematology Service, Departments of Oncology and Laboratory Medicine, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland.
⁶ Department of Orthopaedics and Traumatology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
⁷ Institute of Pathology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and Lausanne University, Lausanne, Switzerland; Department of Pathology, Hospital 12 de Octubre, Madrid, Spain.
⁸ Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts.
⁹ Institute of Pathology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and Lausanne University, Lausanne, Switzerland; Institute of Pathology, Ente Ospedaliero Cantonale (EOC), Locarno, Switzerland.
¹⁰ Bioinformatics Competence Center (BICC), UNIL/EPFL Lausanne, Switzerland.
¹¹ Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
¹² Laboratory of Systems Biology and Genetics, Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL) and Swiss Institute of Bioinformatics, Lausanne, Switzerland.
¹³ Laboratory of Regenerative Hematopoiesis, Institute of Bioengineering & ISREC, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland; Hematology Service, Departments of Oncology and Laboratory Medicine, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland. Electronic address: olaia.naveiras@unil.ch.

PMID: 36788087
DOI: 10.1016/j.modpat.2022.100088

Abstract

Bone marrow (BM) cellularity assessment is a crucial step in the evaluation of BM trephine biopsies for hematologic and nonhematologic disorders. Clinical assessment is based on a semiquantitative visual estimation of the hematopoietic and adipocytic components by hematopathologists, which does not provide quantitative information on other stromal compartments. In this study, we developed and validated MarrowQuant 2.0, an efficient, user-friendly digital hematopathology workflow integrated within QuPath software, which serves as BM quantifier for 5 mutually exclusive compartments (bone, hematopoietic, adipocytic, and interstitial/microvasculature areas and other) and derives the cellularity of human BM trephine biopsies. Instance segmentation of individual adipocytes is realized through the adaptation of the machine-learning-based algorithm StarDist. We calculated BM compartments and adipocyte size distributions of hematoxylin and eosin images obtained from 250 bone specimens, from control subjects and patients with acute myeloid leukemia or myelodysplastic syndrome, at diagnosis and follow-up, and measured the agreement of cellularity estimates by MarrowQuant 2.0 against visual scores from 4 hematopathologists. The algorithm was capable of robust BM compartment segmentation with an average mask accuracy of 86%, maximal for bone (99%), hematopoietic (92%), and adipocyte (98%) areas. MarrowQuant 2.0 cellularity score and hematopathologist estimations were highly correlated (R² = 0.92-0.98, intraclass correlation coefficient [ICC] = 0.98; interobserver ICC = 0.96). BM compartment segmentation quantitatively confirmed the reciprocity of the hematopoietic and adipocytic compartments. MarrowQuant 2.0 performance was additionally tested for cellularity assessment of specimens prospectively collected from clinical routine diagnosis. After special consideration for the choice of the cellularity equation in specimens with expanded stroma, performance was similar in this setting (R² = 0.86, n = 42). Thus, we conclude that these validation experiments establish MarrowQuant 2.0 as a reliable tool for BM cellularity assessment. We expect this workflow will serve as a clinical research tool to explore novel biomarkers related to BM stromal components and may contribute to further validation of future digitalized diagnostic hematopathology workstreams.

Keywords: adiposity; bone marrow; cellularity; digital pathology; hematopathology; open-source; stroma.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Bone Marrow Cells / pathology
Bone Marrow Examination
Bone Marrow* / pathology
Hematology*
Humans
Workflow