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Liver fibrosis and tissue architectural change measurement using fractal-rectified metrics and Hurst's exponent

World Journal of Gastroenterology 2006年第14期12卷 2187-2194页

作者： Nicola Dioguardi Fabio Grizzi Barbara Franceschini Paola Bossi Carlo Russo Laboratori di Medicina Quantitativa Istituto Clinico Humanitas IRCCS RozzanoMilanand "Michele Rodriguez" FoundationInstitute for Quantitative Methods in MedicineMilanItaly Department of Pathology Istituto Clinico Humanitas IRCCS RozzanoMilanItaly

AIM： To provide the accurate alternative metrical means of monitoring the effects of new antiviral drugs on the reversal of newly formed collagen. METHODS： Digitized histological biopsy sections taken from 209 patients with chronic C virus hepatitis with different grade of fibrosis or cirrhosis, were measured by means of a new, rapid, user-friendly, fully computeraided method based on the international system meter rectified using fractal principles. RESULTS： The following were described： geometric perimeter, area and wrinkledness of fibrosis; the collation of the Knodell, Sheuer, Ishak and METAVIR scores with fractal-rectified metric measurements; the meaning of the physical composition of fibrosis in relation to the magnitude of collagen islets; the intra- and inter-biopsy sample variability of these parameters; the ＂staging＂ of biopsy sections indicating the pathway covered by fibrosis formation towards its maximum known value; the quantitative liver tissue architectural changes with the Hurst exponent. CONCLUSION： Our model provides the first metrical evaluations of the geometric properties of fibrosis and the quantitative architectural changes of the liver tissue. The representativeness of histological sections of the whole liver is also discussed in the light of the results obtained with the Hurst coefficient.

关键词： Liver Fibrosis Cirrhosis Staging Image analysis Fractals

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Computer-aided morphometry of liver inflammation in needle biopsies

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World Journal of Gastroenterology 2005年第44期11卷 6995-7000页

作者： N Dioguardi B Franceschini C Russo F Grizzi Scientific Direction

AIM: To introduce a computer-aided morphometric method for quantifying the necro-inflammatory phase in liver biopsy specimens using fractal geometry and Delaunay's ***: Two-micrometer thick biopsy sections taken from 78 chronic hepatitis C virus-infected patients were immunohistochemically treated to identify the inflammatory cells. An automatic computer-aided image analysis system was used to define the inflammatory cell network defined on the basis of Delaunay's triangulation,and the inflammatory cells were geometrically classified as forming a cluster (an aggregation of a minimum of three cells) or as being irregularly distributed within the tissue. The phase of inflammatory activity was estimated using Hurst's ***: The proposed automatic method was rapid and objective. It could not only provide rigorous results expressed by scalar numbers, but also allow the state of the whole organ to be represented by Hurst's exponent with an error of no more than 12%.CONCLUSION: The availability of rigorous metrical measures and the reasonable representativeness of the status of the organ as a whole raise the question as to whether the indication for hepatic biopsy should be revised by establishing clear rules concerning the contraindications suggested by its invasiveness and subjective interpretation.

关键词： Biopsy Grading Image analysis Fractal geometry Topography Delaunay

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Sampling variability of computer-aided fractal-corrected measures of liver fibrosis in needle biopsy specimens

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World Journal of Gastroenterology 2006年第47期12卷 7660-7665页

作者： Fabio Grizzi Carlo Russo Barbara Franceschini Mariagrazia Di Rocco Valter Torri Emanuela Morenghi Luigi Rainiero Fassati Nicola Dioguardi Laboralori di Medicina Quanlitativa Islituto Clinico Humanitas IRCCS Rozzano Milan Italy Department of Pathology Istituto ClinicoHumanitas IRCCS Rozzano Milan Italy Laboratory of Clinical Research in Oncology Mario Negri Institute of Pharmacological Research Milan Italy Clinical Research Office Istituto ClinicoHumanitas IRCCS Rozzano Milan Italy Department of General Surgery and Transplantation Ospedale Maggiore IRCCS Milan Italy

AIM： TO assess the sampling variability of computeraided, fractal-corrected measures of fibrosis in liver biopsies. METHODS： Samples were derived from six to eight different parts of livers removed from 12 patients with clinically and histologically proven cirrhosis undergoing orthotopic liver transplantation. Sirius red-stained sections with a thickness of 2 μm were digitized using a computer-aided image analysis system that automatically measures the surface of fibrosis, as well as its outline perimeter, fractal surface and outline dimensions, wrinldedness, and Hurst coefficient. RESULTS： We found a high degree of inter-sample variability in the measurements of the surface [coefficient of variation （CV） = 43% ± 13%] and wrinkledness （CV = 28% ± 9%） of fibrosis, but the inter-sample variability of Hurst＇s exponent was low （CV = 14% ± 2%）. CONCLUSION： This study suggests that Hurst＇s exponent might be used in clinical practice as the best histological estimate of fibrosis in the whole organ, and evidences the fact that biopsy sections, which are fundamental for the qualitative diagnosis of chronic hepatitis, play a key role in the quantitative estimate of architectural changes in liver tissue.

关键词： Cirrhosis Hepatitis C virus Inter-sample variability Extra-cellular matrix Image analysis

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Metrically measuring liver biopsy:A chronic hepatitis B and C computer-aided morphologic description

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World Journal of Gastroenterology 2008年第48期14卷 7335-7344页

作者： Nicola Dioguardi Fabio Grizzi Barbara Fiamengo Carlo Russo Laboratories of Quantitative Medicine Istituto Clinico Humanitas IRCCS Department of Pathology Istituto Clinico Humanitas IRCCS

AIM： To describe a quantitative analysis method for liver biopsy sections with a machine that we have named ＂Dioguardi Histological Metriser＂ which automatically measures the residual hepatocyte mass （including hepatocytes vacuolization）, inflammation, fibrosis and the loss of liver tissue ***： We analysed digitised images of liver biopsy sections taken from 398 patients, The analysis with Dioguardi Histological Metriser was validated by comparison with semi-quantitative scoring ***： The method provides：（1） the metrical extension in two-dimensions （the plane） of the residual hepatocellular set, including the area of vacuoles pertinent to abnormal lipid accumulation; （2） the geo- metric measure of the inflammation basin, which distinguishes intra-basin space and extra-basin dispersed parenchymal leukoo/tes; （3） the magnitude of collagen islets, （which were considered truncated fractals and classified into three degrees of magnitude）; and （4） the tectonic index that quantifies alterations （disorders） in the organization of liver tissue. Dioguardi Histological Metriser machine allows to work at a speed of 0.1 mm^2/s, scanning a whole section in 6-8 ***： The results are the first standardized metrical evaluation of the geometric properties of the parenchyma, inflammation, fibrosis, and alterations in liver tissue tectonics of the biopsy sections. The present study confirms that biopsies are still valuable, not only for diagnosing chronic hepatitis, but also for quantifying changes in the organization and order of liver tissue structure.

关键词： Liver measurement Image analysis Liverlesion Liver tectonics

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