Automated Digital Quantification of Pulmonary Fibrosis in Human Histopathology Specimens

Overview

Journal Front Med (Lausanne)

Specialty General Medicine

Date 2021 Jul 2

PMID 34211981

Citations 11

Authors

Lauren C Testa

Yvon Jule

Linnea Lundh

Karine Bertotti

Melissa A Merideth

Kevin J OBrien

Steven D Nathan

Drew C Venuto

Souheil El-Chemaly

May Christine V Malicdan

Bernadette R Gochuico

Affiliations

Soon will be listed here.

Abstract

Pulmonary fibrosis is characterized by abnormal interstitial extracellular matrix and cellular accumulations. Methods quantifying fibrosis severity in lung histopathology samples are semi-quantitative, subjective, and analyze only portions of sections. We sought to determine whether automated computerized imaging analysis shown to continuously measure fibrosis in mice could also be applied in human samples. A pilot study was conducted to analyze a small number of specimens from patients with Hermansky-Pudlak syndrome pulmonary fibrosis (HPSPF) or idiopathic pulmonary fibrosis (IPF). Digital images of entire lung histological serial sections stained with picrosirius red and alcian blue or anti-CD68 antibody were analyzed using dedicated software to automatically quantify fibrosis, collagen, and macrophage content. Automated fibrosis quantification based on parenchymal tissue density and fibrosis score measurements was compared to pulmonary function values or Ashcroft score. Automated fibrosis quantification of HPSPF lung explants was significantly higher than that of IPF lung explants or biopsies and was also significantly higher in IPF lung explants than in IPF biopsies. A high correlation coefficient was found between some automated quantification measurements and lung function values for the three sample groups. Automated quantification of collagen content in lung sections used for digital image analyses was similar in the three groups. CD68 immunolabeled cell measurements were significantly higher in HPSPF explants than in IPF biopsies. In conclusion, computerized image analysis provides access to accurate, reader-independent pulmonary fibrosis quantification in human histopathology samples. Fibrosis, collagen content, and immunostained cells can be automatically and individually quantified from serial sections. Robust automated digital image analysis of human lung samples enhances the available tools to quantify and study fibrotic lung disease.

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References

Ashcroft T, Simpson J, Timbrell V . Simple method of estimating severity of pulmonary fibrosis on a numerical scale. J Clin Pathol. 1988; 41(4):467-70. PMC: 1141479. DOI: 10.1136/jcp.41.4.467. View

King Jr T, Bradford W, Castro-Bernardini S, Fagan E, Glaspole I, Glassberg M . A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med. 2014; 370(22):2083-92. DOI: 10.1056/NEJMoa1402582. View

Gilhodes J, Jule Y, Kreuz S, Stierstorfer B, Stiller D, Wollin L . Quantification of Pulmonary Fibrosis in a Bleomycin Mouse Model Using Automated Histological Image Analysis. PLoS One. 2017; 12(1):e0170561. PMC: 5249201. DOI: 10.1371/journal.pone.0170561. View

Martinez F, Collard H, Pardo A, Raghu G, Richeldi L, Selman M . Idiopathic pulmonary fibrosis. Nat Rev Dis Primers. 2017; 3:17074. DOI: 10.1038/nrdp.2017.74. View

Albadrani M, Seth R, Sarkar S, Kimono D, Mondal A, Bose D . Exogenous PP2A inhibitor exacerbates the progression of nonalcoholic fatty liver disease via NOX2-dependent activation of miR21. Am J Physiol Gastrointest Liver Physiol. 2019; 317(4):G408-G428. PMC: 6842990. DOI: 10.1152/ajpgi.00061.2019. View

OBrien K, Introne W, Akal O, Akal T, Barbu A, McGowan M . Prolonged treatment with open-label pirfenidone in Hermansky-Pudlak syndrome pulmonary fibrosis. Mol Genet Metab. 2018; 125(1-2):168-173. DOI: 10.1016/j.ymgme.2018.07.012. View

Barisoni L, Lafata K, Hewitt S, Madabhushi A, Balis U . Digital pathology and computational image analysis in nephropathology. Nat Rev Nephrol. 2020; 16(11):669-685. PMC: 7447970. DOI: 10.1038/s41581-020-0321-6. View

Richeldi L, du Bois R, Raghu G, Azuma A, Brown K, Costabel U . Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med. 2014; 370(22):2071-82. DOI: 10.1056/NEJMoa1402584. View

Vicary G, Vergne Y, Santiago-Cornier A, Young L, Roman J . Pulmonary Fibrosis in Hermansky-Pudlak Syndrome. Ann Am Thorac Soc. 2016; 13(10):1839-1846. PMC: 5466158. DOI: 10.1513/AnnalsATS.201603-186FR. View

10.

Richeldi L, Collard H, Jones M . Idiopathic pulmonary fibrosis. Lancet. 2017; 389(10082):1941-1952. DOI: 10.1016/S0140-6736(17)30866-8. View

11.

Haroutunian S, OBrien K, Estrada-Veras J, Yao J, Boyd L, Mathur K . Clinical and Histopathologic Features of Interstitial Lung Disease in Erdheim⁻Chester Disease. J Clin Med. 2018; 7(9). PMC: 6162862. DOI: 10.3390/jcm7090243. View

12.

Raghu G, Remy-Jardin M, Myers J, Richeldi L, Ryerson C, Lederer D . Diagnosis of Idiopathic Pulmonary Fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med. 2018; 198(5):e44-e68. DOI: 10.1164/rccm.201807-1255ST. View

13.

Witkop C, Nunez Babcock M, Rao G, Gaudier F, Summers C, Shanahan F . Albinism and Hermansky-Pudlak syndrome in Puerto Rico. Bol Asoc Med P R. 1990; 82(8):333-9. View

14.

Trimble A, Gochuico B, Markello T, Fischer R, Gahl W, Lee J . Circulating fibrocytes as biomarker of prognosis in Hermansky-Pudlak syndrome. Am J Respir Crit Care Med. 2014; 190(12):1395-401. PMC: 4299649. DOI: 10.1164/rccm.201407-1287OC. View

15.

Brantly M, Avila N, Shotelersuk V, Lucero C, Huizing M, Gahl W . Pulmonary function and high-resolution CT findings in patients with an inherited form of pulmonary fibrosis, Hermansky-Pudlak syndrome, due to mutations in HPS-1. Chest. 2000; 117(1):129-36. DOI: 10.1378/chest.117.1.129. View

16.

Gochuico B, Huizing M, Golas G, Scher C, Tsokos M, Denver S . Interstitial lung disease and pulmonary fibrosis in Hermansky-Pudlak syndrome type 2, an adaptor protein-3 complex disease. Mol Med. 2011; 18:56-64. PMC: 3269640. DOI: 10.2119/molmed.2011.00198. View

17.

Power B, Ferreira C, Chen D, Zein W, OBrien K, Introne W . Hermansky-Pudlak syndrome and oculocutaneous albinism in Chinese children with pigmentation defects and easy bruising. Orphanet J Rare Dis. 2019; 14(1):52. PMC: 6385472. DOI: 10.1186/s13023-019-1023-7. View

18.

Heinemann F, Birk G, Schoenberger T, Stierstorfer B . Deep neural network based histological scoring of lung fibrosis and inflammation in the mouse model system. PLoS One. 2018; 13(8):e0202708. PMC: 6107205. DOI: 10.1371/journal.pone.0202708. View

19.

El-Chemaly S, OBrien K, Nathan S, Weinhouse G, Goldberg H, Connors J . Clinical management and outcomes of patients with Hermansky-Pudlak syndrome pulmonary fibrosis evaluated for lung transplantation. PLoS One. 2018; 13(3):e0194193. PMC: 5856338. DOI: 10.1371/journal.pone.0194193. View

20.

De Rudder M, Bouzin C, Nachit M, Louvegny H, Velde G, Jule Y . Automated computerized image analysis for the user-independent evaluation of disease severity in preclinical models of NAFLD/NASH. Lab Invest. 2019; 100(1):147-160. DOI: 10.1038/s41374-019-0315-9. View