Stereological analysis of liver biopsy histology sections as a reference standard for validating non-invasive liver fat fraction measurements by MRI

Tim St Pierre, Mike J. House, S.J. Bangma, W. Pang, A. Bathgate, Eng K. Gan, Oyekoya T. Ayonrinde, P.S. Bhathal, A. Clouston, John Olynyk, Leon A. Adams

    Research output: Contribution to journalArticle

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    Abstract

    © 2016 St. Pierre et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background and Aims: Validation of non-invasive methods of liver fat quantification requires a reference standard. However, using standard histopathology assessment of liver biopsies is problematical because of poor repeatability. We aimed to assess a stereological method of measuring volumetric liver fat fraction (VLFF) in liver biopsies and to use the method to validate a magnetic resonance imaging method for measurement of VLFF. Methods: VLFFs were measured in 59 subjects (1) by three independent analysts using a stereological point counting technique combined with the Delesse principle on liver biopsy histological sections and (2) by three independent analysts using the HepaFat-Scan® technique on magnetic resonance images of the liver. Bland Altman statistics and intraclass correlation (IC) were used to assess the repeatability of each method and the bias between the methods of liver fat fraction measurement. Results: Inter-analyst repeatability coefficients for the stereology and HepaFat-Scan® methods were 8.2 (95% CI 7.7-8.8)% and 2.4 (95% CI 2.2-2.5)% VLFF respectively. IC coefficients were 0.86 (95% CI 0.69-0.93) and 0.990 (95% CI 0.985-0.994) respectively. Small biases (≤3.4%) were observable between two pairs of analysts using stereology while no significant biases were observable between any of the three pairs of analysts using Hepa-Fat-Scan®. A bias of 1.4±0.5% VLFF was observed between the HepaFat-Scan® method and the stereological method. Conclusions: Repeatability of the stereological method is superior to the previously reported performance of assessment of hepatic steatosis by histopathologists and is a suitable reference standard for validating non-invasive methods of measurement of VLFF.
    Original languageEnglish
    Article numbere0160789
    JournalPLoS One
    Volume11
    Issue number8
    DOIs
    Publication statusPublished - 2016

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    Histology
    Biopsy
    reference standards
    Liver
    Magnetic resonance imaging
    histology
    biopsy
    Fats
    liver
    lipids
    repeatability
    methodology
    Magnetic resonance
    Licensure
    fatty liver
    Reproduction
    magnetic resonance imaging
    histopathology
    Magnetic Resonance Spectroscopy
    Statistics

    Cite this

    @article{aaef94a2c29b4180ad2bdb7ba785242b,
    title = "Stereological analysis of liver biopsy histology sections as a reference standard for validating non-invasive liver fat fraction measurements by MRI",
    abstract = "{\circledC} 2016 St. Pierre et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background and Aims: Validation of non-invasive methods of liver fat quantification requires a reference standard. However, using standard histopathology assessment of liver biopsies is problematical because of poor repeatability. We aimed to assess a stereological method of measuring volumetric liver fat fraction (VLFF) in liver biopsies and to use the method to validate a magnetic resonance imaging method for measurement of VLFF. Methods: VLFFs were measured in 59 subjects (1) by three independent analysts using a stereological point counting technique combined with the Delesse principle on liver biopsy histological sections and (2) by three independent analysts using the HepaFat-Scan{\circledR} technique on magnetic resonance images of the liver. Bland Altman statistics and intraclass correlation (IC) were used to assess the repeatability of each method and the bias between the methods of liver fat fraction measurement. Results: Inter-analyst repeatability coefficients for the stereology and HepaFat-Scan{\circledR} methods were 8.2 (95{\%} CI 7.7-8.8){\%} and 2.4 (95{\%} CI 2.2-2.5){\%} VLFF respectively. IC coefficients were 0.86 (95{\%} CI 0.69-0.93) and 0.990 (95{\%} CI 0.985-0.994) respectively. Small biases (≤3.4{\%}) were observable between two pairs of analysts using stereology while no significant biases were observable between any of the three pairs of analysts using Hepa-Fat-Scan{\circledR}. A bias of 1.4±0.5{\%} VLFF was observed between the HepaFat-Scan{\circledR} method and the stereological method. Conclusions: Repeatability of the stereological method is superior to the previously reported performance of assessment of hepatic steatosis by histopathologists and is a suitable reference standard for validating non-invasive methods of measurement of VLFF.",
    author = "{St Pierre}, Tim and House, {Mike J.} and S.J. Bangma and W. Pang and A. Bathgate and Gan, {Eng K.} and Ayonrinde, {Oyekoya T.} and P.S. Bhathal and A. Clouston and John Olynyk and Adams, {Leon A.}",
    year = "2016",
    doi = "10.1371/journal.pone.0160789",
    language = "English",
    volume = "11",
    journal = "P L o S One",
    issn = "1932-6203",
    publisher = "Public Library of Science (PLoS)",
    number = "8",

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    Stereological analysis of liver biopsy histology sections as a reference standard for validating non-invasive liver fat fraction measurements by MRI. / St Pierre, Tim; House, Mike J.; Bangma, S.J.; Pang, W.; Bathgate, A.; Gan, Eng K.; Ayonrinde, Oyekoya T.; Bhathal, P.S.; Clouston, A.; Olynyk, John; Adams, Leon A.

    In: PLoS One, Vol. 11, No. 8, e0160789, 2016.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Stereological analysis of liver biopsy histology sections as a reference standard for validating non-invasive liver fat fraction measurements by MRI

    AU - St Pierre, Tim

    AU - House, Mike J.

    AU - Bangma, S.J.

    AU - Pang, W.

    AU - Bathgate, A.

    AU - Gan, Eng K.

    AU - Ayonrinde, Oyekoya T.

    AU - Bhathal, P.S.

    AU - Clouston, A.

    AU - Olynyk, John

    AU - Adams, Leon A.

    PY - 2016

    Y1 - 2016

    N2 - © 2016 St. Pierre et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background and Aims: Validation of non-invasive methods of liver fat quantification requires a reference standard. However, using standard histopathology assessment of liver biopsies is problematical because of poor repeatability. We aimed to assess a stereological method of measuring volumetric liver fat fraction (VLFF) in liver biopsies and to use the method to validate a magnetic resonance imaging method for measurement of VLFF. Methods: VLFFs were measured in 59 subjects (1) by three independent analysts using a stereological point counting technique combined with the Delesse principle on liver biopsy histological sections and (2) by three independent analysts using the HepaFat-Scan® technique on magnetic resonance images of the liver. Bland Altman statistics and intraclass correlation (IC) were used to assess the repeatability of each method and the bias between the methods of liver fat fraction measurement. Results: Inter-analyst repeatability coefficients for the stereology and HepaFat-Scan® methods were 8.2 (95% CI 7.7-8.8)% and 2.4 (95% CI 2.2-2.5)% VLFF respectively. IC coefficients were 0.86 (95% CI 0.69-0.93) and 0.990 (95% CI 0.985-0.994) respectively. Small biases (≤3.4%) were observable between two pairs of analysts using stereology while no significant biases were observable between any of the three pairs of analysts using Hepa-Fat-Scan®. A bias of 1.4±0.5% VLFF was observed between the HepaFat-Scan® method and the stereological method. Conclusions: Repeatability of the stereological method is superior to the previously reported performance of assessment of hepatic steatosis by histopathologists and is a suitable reference standard for validating non-invasive methods of measurement of VLFF.

    AB - © 2016 St. Pierre et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background and Aims: Validation of non-invasive methods of liver fat quantification requires a reference standard. However, using standard histopathology assessment of liver biopsies is problematical because of poor repeatability. We aimed to assess a stereological method of measuring volumetric liver fat fraction (VLFF) in liver biopsies and to use the method to validate a magnetic resonance imaging method for measurement of VLFF. Methods: VLFFs were measured in 59 subjects (1) by three independent analysts using a stereological point counting technique combined with the Delesse principle on liver biopsy histological sections and (2) by three independent analysts using the HepaFat-Scan® technique on magnetic resonance images of the liver. Bland Altman statistics and intraclass correlation (IC) were used to assess the repeatability of each method and the bias between the methods of liver fat fraction measurement. Results: Inter-analyst repeatability coefficients for the stereology and HepaFat-Scan® methods were 8.2 (95% CI 7.7-8.8)% and 2.4 (95% CI 2.2-2.5)% VLFF respectively. IC coefficients were 0.86 (95% CI 0.69-0.93) and 0.990 (95% CI 0.985-0.994) respectively. Small biases (≤3.4%) were observable between two pairs of analysts using stereology while no significant biases were observable between any of the three pairs of analysts using Hepa-Fat-Scan®. A bias of 1.4±0.5% VLFF was observed between the HepaFat-Scan® method and the stereological method. Conclusions: Repeatability of the stereological method is superior to the previously reported performance of assessment of hepatic steatosis by histopathologists and is a suitable reference standard for validating non-invasive methods of measurement of VLFF.

    U2 - 10.1371/journal.pone.0160789

    DO - 10.1371/journal.pone.0160789

    M3 - Article

    VL - 11

    JO - P L o S One

    JF - P L o S One

    SN - 1932-6203

    IS - 8

    M1 - e0160789

    ER -