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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
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 red...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The British Institute of Radiology.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8320116/ https://www.ncbi.nlm.nih.gov/pubmed/34381940 http://dx.doi.org/10.1259/bjro.20210006 |
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author | Wang, Li Ming Jung, Sungmi Serban, Monica Chatterjee, Avishek Lee, Sangkyu Jeyaseelan, Krishinima El Naqa, Issam Seuntjens, Jan Ybarra, Norma |
author_facet | Wang, Li Ming Jung, Sungmi Serban, Monica Chatterjee, Avishek Lee, Sangkyu Jeyaseelan, Krishinima El Naqa, Issam Seuntjens, Jan Ybarra, Norma |
author_sort | Wang, Li Ming |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8320116 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | The British Institute of Radiology. |
record_format | MEDLINE/PubMed |
spelling | pubmed-83201162021-08-10 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 Wang, Li Ming Jung, Sungmi Serban, Monica Chatterjee, Avishek Lee, Sangkyu Jeyaseelan, Krishinima El Naqa, Issam Seuntjens, Jan Ybarra, Norma BJR Open Original Research 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. The British Institute of Radiology. 2021-07-05 /pmc/articles/PMC8320116/ /pubmed/34381940 http://dx.doi.org/10.1259/bjro.20210006 Text en © 2021 The Authors. Published by the British Institute of Radiology https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Original Research Wang, Li Ming Jung, Sungmi Serban, Monica Chatterjee, Avishek Lee, Sangkyu Jeyaseelan, Krishinima El Naqa, Issam Seuntjens, Jan Ybarra, Norma 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 |
title | 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 |
title_full | 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 |
title_fullStr | 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 |
title_full_unstemmed | 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 |
title_short | 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 |
title_sort | 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 |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8320116/ https://www.ncbi.nlm.nih.gov/pubmed/34381940 http://dx.doi.org/10.1259/bjro.20210006 |
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