Comparison of quantitative and qualitative scoring approaches for radiation-induced pulmonary fibrosis as applied to a preliminary investigation into the efficacy of mesenchymal stem cell delivery methods in a rat model

Li Ming Wang; Sungmi Jung; Monica Serban; Avishek Chatterjee; Sangkyu Lee; Krishinima Jeyaseelan; Issam El Naqa; Jan Seuntjens; Norma Ybarra

doi:10.1259/bjro.20210006

Comparison of quantitative and qualitative scoring approaches for radiation-induced pulmonary fibrosis as applied to a preliminary investigation into the efficacy of mesenchymal stem cell delivery methods in a rat model

BJR Open. 2021 Jul 5;2(1):20210006. doi: 10.1259/bjro.20210006. eCollection 2021.

Authors

Li Ming Wang¹, Sungmi Jung², Monica Serban³, Avishek Chatterjee³, Sangkyu Lee⁴, Krishinima Jeyaseelan³, Issam El Naqa⁵, Jan Seuntjens⁶, Norma Ybarra⁷

Affiliations

¹ Research Institute of the McGill University Healthcare Centre, Montréal, Canada.
² Department of Pathology, McGill University Healthcare Centre, Montréal, Canada.
³ Medical Physics Unit, Cedars Cancer Centre, McGill University Healthcare Centre, Montréal, Canada.
⁴ Memorial Sloan Kettering Cancer Centre, New York, NY, USA.
⁵ Radiation Oncology, University of Michigan - Ann Arbor, Ann Arbor, MI, USA.
⁶ Medical Physics Unit, Cedars Cancer Centre, Montréal University Healthcare Centre, Montreal, Canada.
⁷ Research Institute of the McGill University Healthcare Centre & Medical Physics Unit, CedarsCancer Centre, McGill University Healthcare Centre, Montreal, Canada.

Abstract

Objectives: Compare a quantitative, algorithm-driven, and qualitative, pathologist-driven, scoring of radiation-induced pulmonary fibrosis (RIPF). And using these scoring models to derive preliminary comparisons on the effects of different mesenchymal stem cell (MSC) administration modalities in reducing RIPF.

Methods: 25 rats were randomized into 5 groups: non-irradiated control (CG), irradiated control (CR), intraperitoneally administered granulocyte-macrophage colony stimulating factor or GM-CSF (Drug), intravascularly administered MSC (IV), and intratracheally administered MSC (IT). All groups, except CG, received an 18 Gy conformal dose to the right lung. Drug, IV and IT groups were treated immediately after irradiation. After 24 weeks of observation, rats were euthanized, their lungs excised, fixed and stained with Masson's Trichrome. Samples were anonymized and RIPF was scored qualitatively by a certified pathologist and quantitatively using ImageScope. An analysis of association was conducted, and two binary classifiers trained to validate the integrity of both qualitative and quantitative scoring. Differences between the treatment groups, as assessed by the pathologist score, were then tested by variance component analysis and mixed models for differences in RIPF outcomes.

Results: There is agreement between qualitative and quantitative scoring for RIPF grades from 4 to 7. Both classifiers performed similarly on the testing set (AUC = 0.923) indicating accordance between the qualitative and quantitative scoring. For comparisons between MSC infusion modalities, the Drug group had better outcomes (mean pathologist scoring of 3.96), correlating with significantly better RIPF outcomes than IV [lower by 0.97, p = 0.047, 95% CI = (0.013, 1.918)] and resulting in an improvement over CR [lower by 0.93, p = 0.037, 95% CI = (0.062, 1.800].

Conclusion: Quantitative image analysis may help in the assessment of therapeutic interventions for RIPF and can serve as a scoring surrogate in differentiating between severe and mild cases of RIPF. Preliminary data demonstrate that the use of GM-CSF was best correlated with lower RIPF severity.

Advances in knowledge: Quantitative image analysis can be a viable supplemental system of quality control and triaging in situations where pathologist work hours or resources are limited. The use of different MSC administration methods can result in different degrees of MSC efficacy and study outcomes.