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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.

ABSTRACT: 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.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.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 HepaFat-Scan®. A bias of 1.4±0.5% VLFF was observed between the HepaFat-Scan® method and the stereological method.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.

SUBMITTER: St Pierre TG

PROVIDER: S-EPMC4976876 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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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 G TG House Michael J MJ Bangma Sander J SJ Pang Wenjie W Bathgate Andrew A Gan Eng K EK Ayonrinde Oyekoya T OT Bhathal Prithi S PS Clouston Andrew A Olynyk John K JK Adams Leon A LA

PloS one 20160808 8

<h4>Background and aims</h4>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.<h4>Methods</h4>VLFFs were measured in 59 subjects (1) by ...[more]

PMID: 27501242

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Project description:Ticks are important ectoparasites that are capable of transmitting multiple classes of pathogens and are currently linked with many emerging tick-borne diseases worldwide. With increasing occurrences of tick-borne diseases in both humans and veterinary species, there is a continuous need to further our understanding of ticks and the pathogens they transmit. Whole tick histology provides a full scope of the tick internal anatomy, allowing researchers to examine multiple organs of interest in a single section. This is in contrast to other techniques that are more commonly utilized in tick-borne disease research, such as electron microscopy and light microscopy of individual organs. There is a lack of literature describing a practical technique to process whole tick histologic sections. Therefore, the current study aims to provide researchers with a workable protocol to prepare high quality paraffin-embedded whole tick histology sections. Amblyomma americanum adults were used as an example species for this study. After a series of pilot experiments using a combination of various fixatives, softening agents and processing techniques, we elected to compare two common fixatives, 10% neutral-buffered formalin (NBF) and Bouin's solution for whole ticks. Equal numbers of A. americanum unfed adults (n = 10/fixative) were processed identically and their whole tick histology coronal sections were individually scored. Higher scores were assigned to whole tick sections that contained more internal organs that are crucial for tick-borne disease research (e.g. salivary glands and midgut), high integrity of tissues and exoskeleton on the section, and good fixation and staining quality of the tissues. The mean total scores for Bouin's-fixed ticks were significantly higher compared to NBF-fixed ticks (p = 0.001). To further assess our preferred technique, we also demonstrated the feasibility of producing high quality whole tick sections for three other common tick species of medical importance (Rhipicephalus sanguineus, Ixodes scapularis, and Dermacentor variabilis) using Bouin's solution. While this technique may require further optimization for other tick species, we described a feasible protocol that uses commonly available tools, reagents and standard histologic equipment. This should allow any investigator to easily make adjustments to this protocol as needed based on their experimental goals.

Project description:ObjectiveTo investigate the diagnostic performance of quantitative ultrasound (US) parameters for the assessment of hepatic steatosis in patients with nonalcoholic fatty liver disease (NAFLD) using magnetic resonance imaging proton density fat fraction (MRI-PDFF) as the reference standard.Materials and methodsIn this single-center prospective study, 120 patients with clinically suspected NAFLD were enrolled between March 2019 and January 2020. The participants underwent US examination for radiofrequency (RF) data acquisition and chemical shift-encoded liver MRI for PDFF measurement. Using the RF data analysis, the attenuation coefficient (AC) based on tissue attenuation imaging (TAI) (AC-TAI) and scatter-distribution coefficient (SC) based on tissue scatter-distribution imaging (TSI) (SC-TSI) were measured. The correlations between the quantitative US parameters (AC and SC) and MRI-PDFF were evaluated using Pearson correlation coefficients. The diagnostic performance of AC-TAI and SC-TSI for detecting hepatic fat contents of ≥ 5% (MRI-PDFF ≥ 5%) and ≥ 10% (MRI-PDFF ≥ 10%) were assessed using receiver operating characteristic (ROC) analysis. The significant clinical or imaging factors associated with AC and SC were analyzed using linear regression analysis.ResultsThe participants were classified based on MRI-PDFF: < 5% (n = 38), 5-10% (n = 23), and ≥ 10% (n = 59). AC-TAI and SC-TSI were significantly correlated with MRI-PDFF (r = 0.659 and 0.727, p < 0.001 for both). For detecting hepatic fat contents of ≥ 5% and ≥ 10%, the areas under the ROC curves of AC-TAI were 0.861 (95% confidence interval [CI]: 0.786-0.918) and 0.835 (95% CI: 0.757-0.897), and those of SC-TSI were 0.964 (95% CI: 0.913-0.989) and 0.935 (95% CI: 0.875-0.972), respectively. Multivariable linear regression analysis showed that MRI-PDFF was an independent determinant of AC-TAI and SC-TSI.ConclusionAC-TAI and SC-TSI derived from quantitative US RF data analysis yielded a good correlation with MRI-PDFF and provided good performance for detecting hepatic steatosis and assessing its severity in NAFLD.

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Project description:Background MRI-derived proton density fat fraction (PDFF) is an accurate, reliable, and safe biologic marker for use in the noninvasive diagnosis of hepatic steatosis in patients with nonalcoholic fatty liver disease (NAFLD). Because of the cost and limited availability of MRI, it is necessary to develop an accurate method to diagnose NAFLD with potential point-of-care access. Purpose To compare the diagnostic accuracy of the quantitative US (QUS) fat fraction (FF) estimator with that of the controlled attenuation parameter (CAP) in the diagnosis of NAFLD using contemporaneous MRI-derived PDFF as the reference standard. Materials and Methods Participants with or suspected of having NAFLD were prospectively recruited at the NAFLD Research Center between July 2015 and July 2019. All participants underwent MRI-derived PDFF measurement, transient elastography with CAP measurement, and QUS. QUS FF was derived using computed QUS parameters from the acquired radiofrequency US data using a calibrated reference phantom. The area under the receiver operating characteristic curve (AUC) was calculated to assess the accuracy of QUS FF and CAP in the diagnosis of hepatic steatosis (defined as MRI-derived PDFF ≥ 5%). AUCs were compared using the DeLong test. Results A total of 123 participants were included (mean age, 52 years ± 13 [SD]; 67 [54%] women). Of these participants, 100 (81%) had MRI-derived PDFF of 5% or more. QUS FF had a significantly higher AUC for diagnosis of NAFLD than did CAP (0.92 [95% CI: 0.87, 0.98] vs 0.79 [95% CI: 0.67, 0.90], P = .03). QUS FF had a sensitivity of 98% (98 of 100) and a specificity of 48% (11 of 23). CAP had a sensitivity of 87% (87 of 100) and a specificity of 57% (13 of 23). Conclusion The quantitative US fat fraction estimator is more accurate than the controlled attenuation parameter in the diagnosis of hepatic steatosis in patients with or suspected of having nonalcoholic fatty liver disease. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Ito in this issue.

Dataset Information

Stereological Analysis of Liver Biopsy Histology Sections as a Reference Standard for Validating Non-Invasive Liver Fat Fraction Measurements by MRI.

Publications

Stereological Analysis of Liver Biopsy Histology Sections as a Reference Standard for Validating Non-Invasive Liver Fat Fraction Measurements by MRI.

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