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Current strategies for quantitating fibrosis in liver biopsy.

Wang Y, Hou JL - Chin. Med. J. (2015)

Bottom Line: Key articles were selected mainly according to their levels of relevance to this topic and citations.Due to its evident sensitivity to sampling variances, morphometric measurement is feasible to be taken as a reliable statistical parameter for the study of a large cohort.Combining state-of-art imaging technology and fundamental principle in Tissue Engineering, structure-based quantitation was recently initiated with a novel proof-of-concept tool, qFibrosis. qFibrosis showed not only the superior performance to CPA in accurately and reproducibly differentiating adjacent stages of fibrosis, but also the possibility for facilitating analysis of fibrotic regression and cirrhosis sub-staging.

View Article: PubMed Central - PubMed

Affiliation: Department of Infectious Diseases, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515; Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, China.

ABSTRACT

Objective: The present mini-review updated the progress in methodologies based on using liver biopsy.

Data sources: Articles for study of liver fibrosis, liver biopsy or fibrosis assessment published on high impact peer review journals from 1980 to 2014.

Study selection: Key articles were selected mainly according to their levels of relevance to this topic and citations.

Results: With the recently mounting progress in chronic liver disease therapeutics, comes by a pressing need for precise, accurate, and dynamic assessment of hepatic fibrosis and cirrhosis in individual patients. Histopathological information is recognized as the most valuable data for fibrosis assessment. Conventional histology categorical systems describe the changes of fibrosis patterns in liver tissue; but the simplified ordinal digits assigned by these systems cannot reflect the fibrosis dynamics with sufficient precision and reproducibility. Morphometric assessment by computer assist digital image analysis, such as collagen proportionate area (CPA), detects change of fibrosis amount in tissue section in a continuous variable, and has shown its independent diagnostic value for assessment of advanced or late-stage of fibrosis. Due to its evident sensitivity to sampling variances, morphometric measurement is feasible to be taken as a reliable statistical parameter for the study of a large cohort. Combining state-of-art imaging technology and fundamental principle in Tissue Engineering, structure-based quantitation was recently initiated with a novel proof-of-concept tool, qFibrosis. qFibrosis showed not only the superior performance to CPA in accurately and reproducibly differentiating adjacent stages of fibrosis, but also the possibility for facilitating analysis of fibrotic regression and cirrhosis sub-staging.

Conclusions: With input from multidisciplinary innovation, liver biopsy assessment as a new "gold standard" is anticipated to substantially support the accelerated progress of Hepatology medicine.

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Basic physical principle of SHG/TPEF imaging (a) and its application in hepatic (b) and renal (c) tissue fibrosis imaging in tissue images (b and c), green signal shows the fibrillar collagen imaged by SHG; red signal show the tissue cells imaged by TPEF. (SHG: Second harmonic generation; TPEF: Two-photon excited fluorescence).
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Figure 3: Basic physical principle of SHG/TPEF imaging (a) and its application in hepatic (b) and renal (c) tissue fibrosis imaging in tissue images (b and c), green signal shows the fibrillar collagen imaged by SHG; red signal show the tissue cells imaged by TPEF. (SHG: Second harmonic generation; TPEF: Two-photon excited fluorescence).

Mentions: Recent advances in biophotonics application in Tissue Engineering provided unique techniques for FC detection. Since the first report of nonlinear imaging of biosamples in 1990,[46] application of multiphoton microscopy, such as the second harmonic generation (SHG) microscopy, has been actively explored in biomedical imaging research.[47484950] The fundamental physical principle of SHG imaging in FC molecule is illustrated in Figure 3. SHG imaging of FC has distinct advantages compared to other imaging modalities,[51] including that tissue samples for imaging can be label-free since SHG signals are generated due to the intrinsic noncentrosymmetric structure of FC molecule; the penetration depth can reach to 200 μm because excitation wavelength for SHG is usually adjusted in the near infrared range; and the known excitation and emission spectral signatures of SHG allows easily and sensitively separating signals of FC from other fluorophores. Due to the unique strength of SHG in FC imaging, combining another nonlinear optical technology of two-photon excited fluorescence (TPEF) for tissue cell imaging, some research groups tried to use SHG/TPEF in animal models of liver fibrosis and validated its technical performance and feasibility for hepatic fibrosis imaging.[5052] The first reported clinical application of SHG/TPEF for CLD hepatic fibrosis measurement was by Guilbert et al. in 2010.[53] The study comprehensively validated the technical feasibility of SHG/TPEF using 107 tissue specimens of mixed etiology. Although employing the special imaging technology, it took CPA for fibrosis analyses, so that in some sense it could be regarded as a technical report rather than a study for improving the accuracy of fibrosis assessment modality per se.


Current strategies for quantitating fibrosis in liver biopsy.

Wang Y, Hou JL - Chin. Med. J. (2015)

Basic physical principle of SHG/TPEF imaging (a) and its application in hepatic (b) and renal (c) tissue fibrosis imaging in tissue images (b and c), green signal shows the fibrillar collagen imaged by SHG; red signal show the tissue cells imaged by TPEF. (SHG: Second harmonic generation; TPEF: Two-photon excited fluorescence).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4837847&req=5

Figure 3: Basic physical principle of SHG/TPEF imaging (a) and its application in hepatic (b) and renal (c) tissue fibrosis imaging in tissue images (b and c), green signal shows the fibrillar collagen imaged by SHG; red signal show the tissue cells imaged by TPEF. (SHG: Second harmonic generation; TPEF: Two-photon excited fluorescence).
Mentions: Recent advances in biophotonics application in Tissue Engineering provided unique techniques for FC detection. Since the first report of nonlinear imaging of biosamples in 1990,[46] application of multiphoton microscopy, such as the second harmonic generation (SHG) microscopy, has been actively explored in biomedical imaging research.[47484950] The fundamental physical principle of SHG imaging in FC molecule is illustrated in Figure 3. SHG imaging of FC has distinct advantages compared to other imaging modalities,[51] including that tissue samples for imaging can be label-free since SHG signals are generated due to the intrinsic noncentrosymmetric structure of FC molecule; the penetration depth can reach to 200 μm because excitation wavelength for SHG is usually adjusted in the near infrared range; and the known excitation and emission spectral signatures of SHG allows easily and sensitively separating signals of FC from other fluorophores. Due to the unique strength of SHG in FC imaging, combining another nonlinear optical technology of two-photon excited fluorescence (TPEF) for tissue cell imaging, some research groups tried to use SHG/TPEF in animal models of liver fibrosis and validated its technical performance and feasibility for hepatic fibrosis imaging.[5052] The first reported clinical application of SHG/TPEF for CLD hepatic fibrosis measurement was by Guilbert et al. in 2010.[53] The study comprehensively validated the technical feasibility of SHG/TPEF using 107 tissue specimens of mixed etiology. Although employing the special imaging technology, it took CPA for fibrosis analyses, so that in some sense it could be regarded as a technical report rather than a study for improving the accuracy of fibrosis assessment modality per se.

Bottom Line: Key articles were selected mainly according to their levels of relevance to this topic and citations.Due to its evident sensitivity to sampling variances, morphometric measurement is feasible to be taken as a reliable statistical parameter for the study of a large cohort.Combining state-of-art imaging technology and fundamental principle in Tissue Engineering, structure-based quantitation was recently initiated with a novel proof-of-concept tool, qFibrosis. qFibrosis showed not only the superior performance to CPA in accurately and reproducibly differentiating adjacent stages of fibrosis, but also the possibility for facilitating analysis of fibrotic regression and cirrhosis sub-staging.

View Article: PubMed Central - PubMed

Affiliation: Department of Infectious Diseases, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515; Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, China.

ABSTRACT

Objective: The present mini-review updated the progress in methodologies based on using liver biopsy.

Data sources: Articles for study of liver fibrosis, liver biopsy or fibrosis assessment published on high impact peer review journals from 1980 to 2014.

Study selection: Key articles were selected mainly according to their levels of relevance to this topic and citations.

Results: With the recently mounting progress in chronic liver disease therapeutics, comes by a pressing need for precise, accurate, and dynamic assessment of hepatic fibrosis and cirrhosis in individual patients. Histopathological information is recognized as the most valuable data for fibrosis assessment. Conventional histology categorical systems describe the changes of fibrosis patterns in liver tissue; but the simplified ordinal digits assigned by these systems cannot reflect the fibrosis dynamics with sufficient precision and reproducibility. Morphometric assessment by computer assist digital image analysis, such as collagen proportionate area (CPA), detects change of fibrosis amount in tissue section in a continuous variable, and has shown its independent diagnostic value for assessment of advanced or late-stage of fibrosis. Due to its evident sensitivity to sampling variances, morphometric measurement is feasible to be taken as a reliable statistical parameter for the study of a large cohort. Combining state-of-art imaging technology and fundamental principle in Tissue Engineering, structure-based quantitation was recently initiated with a novel proof-of-concept tool, qFibrosis. qFibrosis showed not only the superior performance to CPA in accurately and reproducibly differentiating adjacent stages of fibrosis, but also the possibility for facilitating analysis of fibrotic regression and cirrhosis sub-staging.

Conclusions: With input from multidisciplinary innovation, liver biopsy assessment as a new "gold standard" is anticipated to substantially support the accelerated progress of Hepatology medicine.

Show MeSH
Related in: MedlinePlus