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Automated Digital Quantification of Pulmonary Fibrosis in Human Histopathology Specimens.

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.

SUBMITTER: Testa LC

PROVIDER: S-EPMC8240807 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundCombined pulmonary fibrosis and emphysema (CPFE) is a heterogeneous clinico-radiological syndrome without a consensus definition. There are limited data on the relation between the amount of parenchymal fibrosis and prognosis. In this study, we assessed the prognostic implications of the extent of fibrosis assessed by an automated quantitative computed tomography (CT) technique and the radiological and functional change over time in patients with a broad spectrum of fibrotic interstitial lung diseases (ILDs) encountered in a real-world setting.MethodsWe conducted a single-centre, retrospective study of 228 consecutive patients with CPFE, encountered from 2007 to 2015 at Kameda Medical Center, Chiba, Japan. We investigated the prognostic value of automated CT fibrosis quantification and the subsequent course of CPFE.ResultsAmong 228 patients with CPFE, 89 had fibrosis affecting < 5% of their lungs, 54 had 5 to < 10% fibrosis, and 85 had ≥ 10% fibrosis at the time of diagnosis. Lower volume of fibrosis correlated with lower rates of mortality and acute exacerbation (p < 0.001). In particular, among those with < 5% fibrosis, only 4.5% died and none experienced acute exacerbation during follow-up, whereas 57.6% and 29.4% of those with ≥ 10% fibrosis experienced death and acute exacerbation, respectively. Although, the ≥ 10% fibrosis group had the poorest overall survival as well as the highest incidence of acute exacerbation, the incidence of decline in pulmonary function tests, change per year in total lung volume, and progression of fibrosis on chest CT was highest in the 5 to < 10% fibrosis group. The Cox proportional hazard model for CPFE progression (defined by composite criteria of death, acute exacerbation, and decline in forced vital capacity or diffusing capacity) showed fibrosis proportion was a risk factor independent of age, sex, smoking pack-years, the Charlson Comorbidity Index, lung cancer, connective tissue disease, and idiopathic pulmonary fibrosis.ConclusionsLess severe (< 5%) fibrosis at baseline was associated with disease stability and better prognosis compared to more severe fibrosis in CPFE occurring with fibrotic ILDs. Further studies including a validation cohort will be needed. Trial Registration Retrospectively registered.

Project description:ObjectivesTo quantify the heterogeneity of fibrosis boundaries in idiopathic pulmonary fibrosis (IPF) using the Gaussian curvature analysis for evaluating disease severity and predicting survival.MethodsWe retrospectively included 104 IPF patients and 52 controls who underwent baseline chest CT scans. Normal lungs below - 500 HU were segmented, and the boundary was three-dimensionally reconstructed using in-house software. Gaussian curvature analysis provided histogram features on the heterogeneity of the fibrosis boundary. We analyzed the correlations between histogram features and the gender-age-physiology (GAP) and CT fibrosis scores. We built a regression model to predict diffusing capacity of carbon monoxide (DLCO) using the histogram features and calculated the modified GAP (mGAP) score by replacing DLCO with the predicted DLCO. The performances of the GAP, CT-GAP, and mGAP scores were compared using 100 repeated random-split sets.ResultsPatients with moderate-to-severe IPF had more numerous Gaussian curvatures at the fibrosis boundary, lower uniformity, and lower 10th to 30th percentiles of Gaussian curvature than controls or patients with mild IPF (all p < 0.0033). The 20th percentile was most significantly correlated with the GAP score (r = - 0.357; p < 0.001) and the CT fibrosis score (r = - 0.343; p = 0.001). More numerous Gaussian curvatures, higher entropy, lower uniformity, and 10th to 30th percentiles (p < 0.001-0.041) were associated with mortality. The mGAP score was comparable to the GAP and CT-GAP scores for survival prediction (mean C-indices, 0.76 vs. 0.79 vs. 0.77, respectively).ConclusionsGaussian curvatures of fibrosis boundaries became more heterogeneous as the disease progressed, and heterogeneity was negatively associated with survival in IPF.Key points• Gaussian curvature of the fibrotic lung boundary was more heterogeneous in patients with moderate-to-severe IPF than those with mild IPF or normal controls. • The 20th percentile of the Gaussian curvature of the fibrosis boundary was linearly correlated with the GAP score and the CT fibrosis score. • A modified GAP score that replaced the diffusing capacity of carbon monoxide with a composite measure using histogram features of the Gaussian curvature of the fibrosis boundary showed a comparable ability to predict survival to both the GAP and the CT-GAP score.

Project description:BackgroundHistological assessment of skeletal muscle sections is important for the research of muscle physiology and diseases. Quantifiable measures of skeletal muscle often include mean fiber diameter, fiber size distribution, and centrally nucleated muscle fibers. These parameters offer insights into the dynamic adaptation of skeletal muscle cells during repeated cycles of degeneration and regeneration associated with many muscle diseases and injuries. Computational programs designed to obtain these parameters would greatly facilitate such efforts and offer significant advantage over manual image analysis, which is very labor-intensive and often subjective. Here, we describe a customized pipeline termed MuscleAnalyzer for muscle histology analysis based upon CellProfiler, a free, open-source software for measuring and analyzing cell images.ResultsThe MuscleAnalyzer pipeline consists of loading, adjusting, and running a series of image-processing modules provided by CellProfiler. This pipeline was evaluated using wild-type and mdx muscle sections co-stained with laminin (to demarcate the muscle fiber boundaries) and 4',6-diamidino-2-phenylindole (DAPI, to label the nuclei). The immunofluorescence images analyzed using the MuscleAnalyzer pipeline or manually yielded similar results in the number of muscle fibers per image (p = 0.42) and central nucleated fiber (CNF) percentage (p = 0.29) in mdx mice. However, for a total of 67 images, CellProfiler completed the analysis in ~ 10 min on a regular PC while it took an investigator ~ 3 h using the manual approach in order to quantify the number of muscle fibers and CNF. Moreover, the MuscleAnalyzer pipeline also provided the measurement of the cross-sectional area (CSA) and minimal Feret's diameter (MFD) of muscle fibers, and thus fiber size distribution can be plotted.ConclusionsOur data indicate that the MuscleAnalyzer pipeline can efficiently and accurately analyze laminin and DAPI co-stained muscle images in a batch format and provide quantitative measurements for muscle histological properties such as muscle fiber diameters, fiber size distribution, and CNF percentage.

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Automated Digital Quantification of Pulmonary Fibrosis in Human Histopathology Specimens.

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